Research

• Research Expenditures in Rheumatology
• Areas of Research
• Clinical Trials
• Basic Research Program
• Clinical Research Program
• Patient Registries

Research Expenditures in Rheumatology and Clinical Immunology

Areas of Research

• Myositis - Polymyositis and Dermatomyositis
• Osteoarthritis
• Rheumatoid Arthritis
• Scleroderma
• Systemic Lupus Erythematosus
• Vasculitis
• Connective Tissue Disease

Myositis - Polymyositis and Dermatomyositis (view clinical trials)

Dr. Oddis' primary research interest includes the clinical, epidemiologic and serologic aspects of idiopathic inflammatory myopathy. He has written extensively on the diagnosis and management of patients with myositis including use of novel immunosuppressive agents such as tacrolimus. Dr. Oddis is the principal investigator on a recently awarded 5-year NIAMS contract (10/04-10/09) to study the efficacy of a novel biologic agent, rituximab, in adult and pediatric myositis. He has been a co-investigator on two NIH-funded osteoarthritis trials; one (DOXY study) tested the efficacy of doxycycline in preventing the progression of knee osteoarthritis in middle-aged women and the second (GAIT) is assessing the effect of glucosamine and chondroitin sulfate on the pain of osteoarthritis and its radiographic progression. He serves as the Director of the Fellowship Training Program and the Medical Director for outpatient services.

View Dr. Oddis' recent publications

Dr. Ascherman's research is currently focused on triggers of autoimmune muscle destruction in polymyositis. Specific goals include the isolation and characterization of Jo-1-reactive T cells in polymyositis patients possessing antibodies against histidyl-tRNA synthetase (Jo-1). Through a combination of in vitro and in vivo models, this work should clarify the pathogenic role of such antigen-specific T cells in Jo-1+ polymyositis patients and potentially set the stage for immunotherapeutic strategies that include altered peptide ligands and TCR-based vaccines.

View Dr. Ascherman's recent publications

Osteoarthritis (view clinical trials)

OA is a non-inflammatory disease that breaks down joint cartilage, causing pain and stiffness. OA usually occurs in weight-bearing joints (such as the hips, knees, spine, back and/or neck), but it also may occur in finger joints, toe joints or the spine. OA is known by many other names, such as degenerative joint disease, arthrosis, osteoarthrosis, and hypertrophic arthritis

Dr. Kwoh's major area of research involves outcome assessment and health services utilization related to osteoarthritis. His work has focused on determinants of ethnic variations in elective total joint replacement and on risk factors for incidence and progression of osteoarthritis.

View Dr. Kwoh's recent publications

Rheumatoid Arthritis (view clinical trials)

Rheumatoid arthritis (RA) is a form of arthritis that has inflammation in the lining of the joints (synovium) and at times in internal organs. This inflammation separates RA from the most common form of arthritis, osteoarthritis. RA can affect any joint with synovium, especially in the hands, feet, knees, shoulders, and hips. The course of RA is variable and unpredictable with damage occurring to joint cartilage, tendons, ligaments, and bone.

Dr. Wasko's clinical research has focused on improvement of long-term outcomes in patients with rheumatoid arthritis (RA). She directs the University's participation in a NIH-funded multi-center longitudinal prospective research study on RA and osteoarthritis patients to monitor current practices of the treatment and their relationship to morbidity and mortality secondary to cardiovascular (CV) disease and malignancy. Dr. Wasko currently is employing noninvasive vascular measures and biomarkers of thromboembolic risk in RA women to detect the prevalence and risk of atherosclerosis. Dr. Wasko directs ongoing clinical trials evaluating efficacy and safety of various new investigational agents in RA

View Dr. Wasko's recent publications

Scleroderma (view clinical trials)

Scleroderma, or systemic sclerosis, is a chronic connective tissue disease classified as one of the autoimmune rheumatic diseases.

The word "scleroderma" comes from two Greek words: "sclero" meaning hard, and "derma" meaning skin. Hardening of the skin is one of the most visible manifestations of the disease. The disease has been called "progressive systemic sclerosis," but the use of that term has been discouraged since it has been found that scleroderma is not necessarily progressive.

Dr. Medsger's research focuses on the epidemiology, clinical and laboratory features and natural history of systemic sclerosis (SSc) and localized forms of scleroderma (LScl), Raynaud disease and polymyositis/dermatomyositis. He and collaborators have described many serologic subsets of SSc and LScl, their distinctive clinical findings, survival and HLA associations. He has developed a SSc disease severity index and has proposed criteria for the classification of early SSc. Current studies include cytokines and other soluble protein markers as SSc disease activity measures, lung transplantation, SSc in twins, childhood onset SSc and LScl and the usefulness and mechanisms of action of D-penicillamine and autologous stem cell transplantation therapy.

view recent publications

Systemic Lupus Erythematosus (view clinical trials)

Lupus is a chronic inflammatory disease that can affect various parts of the body, especially the skin, joints, blood, and kidneys. The body's immune system normally makes proteins called antibodies to protect the body against viruses, bacteria, and other foreign materials. These foreign materials are called antigens. In an autoimmune disorder such as lupus, the immune system loses its ability to tell the difference between foreign substances (antigens) and its own cells and tissues. The immune system then makes antibodies directed against "self." These antibodies, called "auto-antibodies," react with the "self" antigens to form immune complexes. The immune complexes build up in the tissues and can cause inflammation, injury to tissues, and pain.

Dr. Ahearn's laboratory is investigating the molecular basis underlying the development of systemic lupus erythematosus (SLE) associated with deficiency of component(s) within the classical pathway of the complement system through studies aimed at clarifying the role of complement-mediated clearance of apoptotic cells and pathogenesis. He is developing a novel assay for diagnosing and monitoring disease activity in SLE and other autoimmune diseases based on the observation that products of complement activation, C4d and C3d, are detected on the surface of erythrocytes and platelets (C4d) of SLE patients at much higher levels and expression of CR1 on erythrocytes is significantly lower in SLE patients than in healthy individuals. Dr. Ahearn is developing both in vitro and in vivo models to dissect the molecular mechanisms through which complement components, influence vascular elasticity and development of premature cardiovascular disease in SLE.

View Dr. Ahearn's recent publications

Dr. Manzi's research focus is on the clinical and epidemiological study of systemic lupus erythematosus (SLE). A major emphasis of Dr. Manzi's research is pathogenesis and associated risk factors of premature cardiovascular disease in young women with SLE. She is also involved in a translational research program examining novel new assays for diagnosis and monitoring of SLE disease activity. Dr. Manzi is actively participating in the Epidemiology of Women's Health curriculum at the Graduate School of Public Health and is involved in training doctoral and postdoctoral candidates in the School of Medicine and Epidemiology.

View Dr. Manzi's recent publications

Dr. Kao's current research includes the study of prevalence and associated risk factors of cardiovascular atherosclerosis in women with SLE and women with rheumatoid arthritis using electron beam tomography and carotid ultrasound. In addition she is investigating complement receptor-ligand assays as biomarkers for diagnosis of SLE and disease activity. She is also involved in several clinical trials in SLE.

View Dr. Kao's recent publications

Dr. Liu's current research concentrates on elucidating the intricate roles of complement proteins, erythrocytes, and T lymphocytes in the pathogenesis of systemic lupus erythematosus (SLE). During SLE flares, split products of complement proteins are generated as the result of complement activation. She has recently found that significant amounts of complement products are deposited on the surface of erythrocytes and T lymphocytes in SLE patients. These findings have prompted visiting the molecular basis of complement-mediated immunopathogenesis in SLE, and investigating the role of complement-bound erythrocytes/reticulocytes as novel biomarkers of SLE disease activity.

View Dr. Liu's recent publications

Vasculitis

The word vasculitis means "inflammation of blood vessels." There are many different types of blood vessels in the body. Any particular vessel is part of a large vascular "tree" that includes large and medium sized arteries and smaller and smallest arterial branches (arterioles). These branches eventually reach all the tissues of the body, delivering oxygen and nutrients to a network of tiny vessels, called capillaries, that also remove wastes. The capillaries drain into the venous system. The smallest veins are venules; these connect like the tributaries of a river to form larger and larger veins.

Vasculitis can affect any of these different types of blood vessels. Inflammation can affect the lining of the vessels (endothelium) or the wall of an artery or vein. The damaged vessel does not function normally, and tissues that the vessel normally serves may then be affected. The effects of vasculitis that result from damage to the blood vessel include decreased function due to decreased blood flow (ischemia), death of some or all of an organ due to absent blood flow (infarction), or bleeding into the skin or other part of the body due to rupture of the blood vessel wall. Because vasculitis is a process that involves inflammation, it is usually accompanied by other features such as fever, or symptoms of involuntary weight loss and fatigue.

Dr. McKinnon has been a part of the Arthritis Institute since July 2004. She received her fellowship training at the Cleveland Clinic, where she developed a special interest in systemic vasculitis and cardiovascular disease in the rheumatic diseases. Although Dr. McKinnon is actively pursuing research in these areas of interest, her primary focus remains providing the best possible care to her patients.

View Dr. McKinnon's recent publications

Connective Tissue Disease

The purpose of this project is to develop and maintain a Rheumatology Biological Specimen Bank of blood and tissue samples and a parallel Research Databank of computerized medical information. This is to support research of the CTDs and the factors that contribute to their onset and course of these diseases.

Inclusion Criteria:
all ages, male or female, diagnosed by a doctor within the Department of Rheumatology with a CTD.

Clinical Trials

• Osteoarthritis
• Myositis
• Rheumatoid Arthritis
• Scleroderma
• Systemic Lupus Erythematosus
• Various Diseases

Development of Biomarker and Functional Assessment Tools to Evaluate the Effect of Glucosamine on Joint Structure/Function and Quality of Life - the JOG Study

Lay Summary
This study tests whether a dietary supplement called "glucosamine", a substance that promotes cartilage growth, can improve symptoms of joint pain and increase the ability to participate in activities for people with long-term, frequent knee pain. The study will also examine whether there is a chemical in urine (a biomarker called CTX-II) and/or changes in the knee that can be seen with special scans called Magnetic Resonance Imaging (MRI) that are related to knee pain. Self-reported symptoms of knee pain will be compared to results from MRI of the knees before and 6 months after taking the supplement. "Biomarkers", which are any substance, structure or process that can be measured in the body that can influence or predict disease will be measured. Specifically, biomarker CTX-II in urine samples taken before, at 3 months, and at 6 months after taking the supplement will be evaluated. Participants must have long term, frequent knee pain, and be between the ages of 35-65 years old. There is also a sub-study to evaluate the effect of glucosamine on the skin.
Contact Person: Jane Schall (412 ) 624-2917
Status: Actively Recruiting

Physician Summary
As cartilage in the knee deteriorates due to aging, wear-and-tear, injury, or disease, joint space narrowing and pain can develop. The loss of articular cartilage arises from an imbalance between cartilage synthesis and cartilage degradation. When cartilage needs to be remodeled, enzymes such as matrix metalloproteinases (MMPs) degrade type II collagen. It now may be possible to use new molecular markers of cartilage degradation to assess the progression of joint loss in comparison with radiographic changes of the knee joint. Urinary excretion of C-terminal cross linking telopeptide of type II collagen (CTX-II) is a new molecular marker of cartilage tissue degradation metabolism.
Skin aging is characterized by a progressive deterioration of functional properties, linked to alteration of dermal connective tissue. Connective tissue is composed of three major classes of macromolecules, including glycosaminoglycans, all of which show age-related decreases. Glucosamine is a natural amino-monosaccharide which is made in the body and it is a biochemical precursor of glycosaminoglycans. As glucosamine is a precursor for glycosaminoglycans, and glycoaminoglycans are a major component not only of joint cartilage, but also of skin, we are interested in exploring whether glucosamine in a beverage might improve skin parameters over time.
The goal of this study will be to develop a biomarker of cartilage synthesis by determining if an inverse relationship exists between alterations in knee cartilage status (volume, thickness, score, joint space narrowing) and urinary excretion of C-terminal cross linking telopeptide of type II collagen (CTX-II). Glucosamine will be used to promote the alterations in cartilage status among study subjects. We will also characterize people who have experienced cartilage loss and/or a reduced functional ability utilizing performance tests and a questionnaire that assesses the difficulty of performing normal activities of daily living. We will then determine if administration of glucosamine can lead to any alteration of function or pain over a six month period. Participants must have long term, frequent knee pain and be between the ages of 35 and 65.
A secondary goal will be to assess the effect of glucosamine on the skin in a small subset of women over a 3 month time period.
Contact Persons: Jane Schall (412 ) 624-2917
Status: Actively Recruiting

Osteoarthritis Initiative

Lay Summary
Dr. Kwoh and his associates are monitoring the onset and progression of knee arthritis in adults aged 45-79. The University of Pittsburgh is one of four clinical centers involved in this study. There are approximately 1175 participants at this center; a total of 5000 participants will take part at the four centers. The purpose of the study is to examine the: onset and progression of knee arthritis in the general population; use of x-ray and magnetic resonance imaging (MRI- a test using magnets to take pictures of the knees) to detect the onset and monitor the progression of knee arthritis; changes in the chemicals in the blood (biomarkers) before the onset and during the progression of knee arthritis; x-ray or MRI studies, blood and genetic markers that can best be used to monitor stages of knee arthritis. Participants have some symptoms and/or risk factors for developing knee arthritis and or have mild knee arthritis on x-ray.
Contact Person: Mary Jansen, RN 383-1344
Status: Recruiting completed

Physician Summary
The Osteoarthritis Initiative (OAI) is a multi-center, longitudinal, observational cohort study. The primary objective of this study is to create a public archive of data, biological samples, and joint images collected over time from a clinically well-characterized population of individuals who are at high risk of progressing to clinically significant osteoarthritis.

The specific aims of the OAI Pittsburgh Clinical Center are:

1. To establish a clinical center, enrolling men and women aged 45-79 years, who are considered high risk for the development of osteoarthritis, into a longitudinal cohort study to characterize the natural history of the onset and progression of osteoarthritis in a generalizable population over 5 years.
2. To provide appropriate clinical (serum, plasma, cells and urine) and radiological materials (radiographic and magnetic resonance images) for evaluation of the validity of joint structural markers of the knee as potential surrogate endpoints for disease.
3. To deposit data, joint images and biological specimens collected from study subjects into a public domain database and repository (established and operated by the study's Data Coordinating Center) to enable evaluation of structural, biochemical and genetic markers by the public and private scientific communities.
Contact Persons: Mary Jansen, RN 383-1344
Status: Recruiting completed

Clinical Centers for the Osteoarthritis Initiative

Lay Summary
Specific Aims of the Study: -examine the onset and progression of knee arthritis in the general population -examine the use of x-ray and magnetic resonance imaging to detect the onset and monitor the progression of knee arthritis -examine the changes in the chemicals in the blood before the onset and during the progression of knee arthritis -ex...

Contact Person: Janet Bonk, (412) 383-1564, jtbonk@pitt.edu
Status: Recruitment completed October, 2005

Improving Longterm Outcomes in Arthritis: ARAMIS 2006

Lay Summary
This study is designed to determine the longterm impact of rheumatoid arthritis and osteoarthritis on affected individuals. Participants will be mailed questionnaires to complete twice a year to address a wide range of questions concerning arthritis outcome, with a focus on medication side effects, the costs of health care, and health conditions possibly associated with arthritis, such as heard disease and cancer. Please contact Adams, outcome assessor, at 412-647-2638, for more information.
Contact Person: Lindy Kilby (412) 647-2638
Status: Recruiting completed

Physician Summary
ARAMIS is a longitudinal observational study on patients with rheumatoid and/ or osteoarthritis. Participants are mailed a health assessment questionnaire (HAQ) twice per year to address a wide range of questions concerning arthritis outcome, with a focus on medication side effects, the cost of health care, and comorbid conditions, such as heart disease and cancer. Subjects must be at least 18 years of age and have a clinical diagnosis of rheumatoid arthritis and/ or osteoarthritis to participate. Subjects do not receive financial compensation for participation.
Contact Persons: Lindy Kilby (412) 647-2638
Status: Actively Recruiting

Rituximab Therapy in Refractory Adult and Juvenile Idiopathic Inflammatory Myopathies

Lay Summary
Polymyositis and dermatomyositis (i.e. myositis) are inflammatory muscle disorders of unknown etiology currently classified under the rubric of idiopathic inflammatory myopathy (IIM). All forms of IIM are characterized by muscle weakness due to inflammation within muscle tissue but other organ systems may be affected in patients with myositis. The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at the National Institutes of Health, IDEC Pharmaceuticals Corp. and Genentech, Inc. are sponsoring the first international multi-center trial to be conducted in both adult and juvenile myositis patients. This study will be directed and coordinated by Dr. Chester Oddis in the Division of Rheumatology and Clinical Immunology at the University of Pittsburgh School of Medicine. The goal of this study is to examine the effectiveness of rituximab (a biological agent that is being increasingly used in the treatment of adult and pediatric autoimmune diseases) in myositis patients. Approximately 20 adult centers and 17 pediatric clinical centers in the United States, Canada, United Kingdom, Czech Republic and Sweden will be enrolling approximately 200 participants between November 2005 and November 2007. Patients that are five years of age and older, with a definite or probable diagnosis of polymyositis or dermatomyositis for at least six months may be eligible to participate.

Contact: Sherrie Pryber, (412) 647-3241
Status: Actively recruiting

RHEUMATOID ARTHRITIS

Improving Longterm Outcomes in Arthritis: ARAMIS 2006

Lay Summary
This study is designed to determine the longterm impact of rheumatoid arthritis and osteoarthritis on affected individuals. Participants will be mailed questionnaires to complete twice a year to address a wide range of questions concerning arthritis outcome, with a focus on medication side effects, the costs of health care, and health conditions possibly associated with arthritis, such as heard disease and cancer. Please contact Adams, outcome assessor, at 412-647-2638, for more information.
Contact Person: Lindy Kilby (412) 647-2638
Status: Recruiting completed

Physician Summary
ARAMIS is a longitudinal observational study on patients with rheumatoid and/ or osteoarthritis. Participants are mailed a health assessment questionnaire (HAQ) twice per year to address a wide range of questions concerning arthritis outcome, with a focus on medication side effects, the cost of health care, and comorbid conditions, such as heart disease and cancer. Subjects must be at least 18 years of age and have a clinical diagnosis of rheumatoid arthritis and/ or osteoarthritis to participate. Subjects do not receive financial compensation for participation.
Contact Persons: Lindy Kilby (412) 647-2638
Status: Recruitment completed

Adherence in RA: Intervention Strategies

Lay Summary
Colleagues at the School of Nursing and Epidemiology and Center for Research in Chronic Diseases are evaluating the effectiveness of various interventions via mail and phone to improve outcomes in RA patients. For more information, please contact Lisa Tamres, study coordinator, at 412-624-7838.
Contact Person : Lisa Tamres, Study Coordinator (412) 624-7838
Status: Actively Recruiting

Physician Summary
Investigator: Dunbar-Jacob, Wasko, Starz, Peele, Schlenk, Sereika
Description: A randomized, controlled study to compare the effects of a multicomponent intervention by phone and self-instruction manual vs. usual care on adherence to medication among poorly adhering patients with RA. The intervention methodology is based upon principles of cognitive social learning theory using a problem solving framework to increase medication adherence. A variety of self-report instruments will measure psychosocial outcomes, exercise habits and barriers, disease activity, and socio-demographic characteristics. Data will be collected on cost effectiveness of each intervention.
Inclusion/Exclusion Criteria: 198 poorly adhering rheumatoid patients will be recruited from 2 clinical practice sites. Inclusion criteria are: age > or =18, 2 years post RA diagnosis, 1 year at practice site, acknowledged adherence difficulty on questionnaire. Exclusion criteria are: inability to read and write English, on prn medications only, dementia by score on mental status exam.
Contact Persons: Lisa Tamres, Study Coordinator (412) 624-7838

Vascular Disease in Women with Rheumatoid Arthritis: Noninvasive Testing and Risk Factor Assessment

Lay Summary
This study is designed to determine the extend of atherosclerosis (hardening of the arteries) and risk factors for heart disease in women over age 60 who have had RA for more than two years. Participants will undergo an interview, brief physical examination, blood tests, and a heart scan. Results are available free of charge to you and your physician. For more information, please contact Lindy Kilby, study coordinator, at 412-647-2638.
Status: Recruitment completed

Physician Summary
The Cardiovascular Disease in Women with Rheumatoid Arthritis (CVRA) Study was designed to examine the relationship between cardiovascular disease (CVD) and rheumatoid arthritis (RA) and to identify the risk factors for CVD in those with RA. The participants in this study are female, at least 30 years of age, and have RA. Initially, participants came to our site to complete a health assessment, which included questions pertaining to past history of heart problems, RA, medication history, and social history. During their visit, the participants had a physical exam, had phlebotomy that included measures of CV risk factors, and had an electron beam tomography (EBT) scan of the coronary arteries and aorta. Those participants less than 60 years of age also had carotid ultrasound for measures of atherosclerosis. Currently, participants are contacted annually by mail to gather updated information regarding their health and medication use.
Contact Person: Lindy Kilby (412) 647-2638 or (866) 647-8281
Status: Recruitment completed

Epidemiology of Cardiovascular Disease in Women with RA

Lay Summary
This trial is designed to determine the extent of atherosclerosis (hardening of the arteries) and risk factors for heart disease in women with RA, ages 30-60. Participants will undergo an interview, brief physical examination, blood tests, a heart scan, and ultrasound of the carotid arteries (blood vessels in the neck). Results are available free of charge to you and your physician. For more information, please contact Lindy Kilby at (412) 647-2638.
Status: Recruitment complete

Physician Summary
The Cardiovascular Disease in Women with Rheumatoid Arthritis (CVRA) Study was designed to examine the relationship between cardiovascular disease (CVD) and rheumatoid arthritis (RA) and to identify the risk factors for CVD in those with RA. The participants in this study are female, at least 30 years of age, and have RA. Initially, participants came to our site to complete a health assessment, which included questions pertaining to past history of heart problems, RA, medication history, and social history. During their visit, the participants had a physical exam, had phlebotomy that included measures of CV risk factors, and had an electron beam tomography (EBT) scan of the coronary arteries and aorta. Those participants less than 60 years of age also had carotid ultrasound for measures of atherosclerosis. Currently, participants are contacted annually by mail to gather updated information regarding their health and medication use.
Contact Person: Lindy Kilby (412) 647-2638 or (866) 647-8281
Status: Recruitment completed

A Multi-Center, Open Label, Continuation Trial of LymphoStat-B Antibody (Monoclonal Anti-BLyS Antibody) in Subjects with Rheumatoid Arthritis (RA) Who Completed the Phase 2 Protocol LBRA01


Lay Summary
This continuation of the Phase II LymphoStat-B trial is open only to those patients who completed the previous 48-week study. In this part of the study, both patients and physicians know the dose of drug that each patient is receiving. This study remains ongoing, and is projected to end in 2010.

Physician Summary
This is a multi-center, open label, continuation of LymphoStat-B in RA subjects who achieved at least an ACR20 response in the previous 48-week Phase 2 study. Subjects will receive 10 mg/kg of LymphoStat-B every 28 days intravenously (IV) over a period of 1 to 2 hours. The first dose of the study agent must be given 4 weeks (+/- 2 weeks) after the last (Day 336/exit) dose in the extension study. The first infusion will be given over 2 hours. If no infusion reactions occur, the 2nd dose will be infused over 1.5 hours. If no infusion reactions occur, the 2nd dose will be infused over 1.5 hours. If nor infusion reactions occurs, then the 3rd and subsequent doses will be infused over 1 hour. The duration of this study is indefinite.
Contact person: Lindy Kilby (412) 647-2638
Status: Recruitment completed

A Randomized, Double-Blind, Placebo-Controlled, Parallel Group of the Safety and Reduction of Signs and Symptoms During Treatment with MRA Versus Placebo, In Combination with Traditional DMARD Therapy in Patients with Moderate to Severe Active Rheumatoid Arthritis and an Inadequate Response to Current DMARD Therapy (WA18063 and WA18063RG)


Lay Summary
This is a study of the safety and reduction of signs and symptoms during treatment with MRA versus placebo, in combination with traditional DMARD therapy in patients with rheumatoid arthritis and an inadequate response to current DMARD therapy.

This is a study of a new drug called MRA that is given intravenously (i.v., through a needle into a vein) over the period of one hour. Potential participants must have active rheumatoid arthritis and currently be on DMARD therapy (disease modifying anti-rheumatic drug). Their current medications are continued throughout the study. They will be dosed with MRA every 4 weeks for 20 weeks and complete the study with 3 follow-up visits in the next 12 weeks for a total of 32 weeks in the study.

The DMARDs subjects may take during this study include:

• Methotrexate
• Chloroquine
• Hydroxychloroquine
• Parenteral gold
• Sulfasalazine
• Azathioprine
• Leflunomide

Combination therapy with methotrexate and leflunomide is not allowed during this study.
Contact person: Linda Kilby (412) 647-2638 of 866-647-8281
Status: Recruitment completed

Long-term extension study of safety during treatment with tocilizumab (MRA) in patients completing treatment in MRA core studies (WA18696)

Lay Summary
This continuation of the Phase III MRA clinical trial is open only to those patients who completed the previous 24-week study. In this part of the study, both patients and physicians know the dose of drug that each patient is receiving. This study remains ongoing, and is projected to end in 2011. Status: Recruiting completed

Physician Summary
This is a Phase III, open-label international multicenter study. All patients who complete study period treatment in the core study (WA18063) will be eligible to enter this long-term extension study. Treatment will consist of tocilizumab (MRA) 8 mg/kg intravenously every four weeks in an open-label fashion. Stable doses of concomitant DMARDs, NSAIDs, and corticosteroids for the treatment of RA will be allowed throughout the trial. Patients will have safety assessments at baseline, weeks 4, 8 and 12, and at 12-weekly intervals for the duration of the study. Additional safety samples will be collected at week 2 and week 6. Treatment will last for 264 weeks (approximately 5 years duration) or until commercial availability, whichever comes first, or until the sponsor decides to discontinue the development program of MRA.
Contact Person: Lindy Kilby (412) 647-2638
Status: Recruitment completed

 A Double Blind, Placebo Controlled, Phase II, Randomized Study of Lovastatin Therapy in the Treatment of Mildly Active Rheumatoid Arthritis

Lay Summary
This is a study of the safety and reduction of signs and symptoms during treatment with lovastatin versus placebo in patients with mildly active rheumatoid arthritis. Patients must have mildly active rheumatoid arthritis to be eligible for this study. Patients will be allowed to continue on most current arthritis medications throughout the study. They will complete a screening visit to determine eligibility; if eligible, they will return within 7 days to receive the study medication. Patients will be asked to return at visit Week (Wk) 2 and Wk 4, then every 4 wk for the rest of this 12-week study. Status: Actively Recruiting

 Physician Summary
This is a double-blind, placebo-controlled, randomized trial determining whether treatment with a statin reduces the serum CRP in subjects with mildly active RA. After obtaining informed consent, patients will complete a screening visit (visit 0) to determine whether inclusion and exclusion entry criteria are fulfilled. Eligible participants will return within 7 days for visit 1 to receive study medication (lovastatin 80 mg/day vs. placebo). Under certain circumstances, the dose may be adjusted. Subjects will return for evaluation at Wk 2 and Wk 4, then every 4 wk for the duration of this 12-wk study. Subjects will be reimbursed $20 per visit for each of the first five study visits and $50 upon completion of the final study visit.
Contact Person: Lindy Kilby (412) 647-2638
Status: Actively Recruiting

 A Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Golimumab, a Fully Human Anti-TNFa Monoclonal Antibody, Administered Subcutaneously, in Subjects with Active Rheumatoid Arthritis and Previously Treated with Biologic Anti-TNFa Agent(s)

Lay Summary
This is a study of the safety and reduction of arthritis activity during treatment with golimumab versus placebo in patients with active rheumatoid arthritis (RA). Golimumab will be given to patients as an injection every 4 weeks (wk). Patients must have active RA and have previously taken an anti-TNF medication (adalimumab/Humira, etanercept/Enbrel, or infliximab/Remicade) to qualify for this study. Patients will be allowed to continue most arthritis medications (most DMARDs and corticosteroids; all NSAIDs) while participating in this study. Patients may NOT continue on anti-TNF drugs listed above or other biologic medications such as rituximab/Rituxan and anakinra/Kineret. Patients will be asked to come to UPMC-Oakland for study visits approximately every 4 wk until Wk 24. Patients will have a 1 in 3 chance of being on placebo during the first 24 wk of this study. If joint swelling and tenderness do not improve by 20% at Wk 16, patients will have an increase in the dose of golimumab or a switch from placebo to golimumab. After Wk 24, patients may enter an extension phase lasting 5 years. During this phase, all patients will receive golimumab. Patients will be trained and allowed to give themselves the injection of study medication during the extension phase and will be asked to return to the site for study visits every 3 months.
Status: Actively Recruiting

Physician Summary
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, 3-arm, parallel study of multiple subcutaneous (SC) doses of golimumab, to evaluate the efficacy and safety of golimumab in subjects with active RA who have been previously treated with anti-TNFa agent(s) by assessing reduction in signs and symptoms of RA at wk 14. Subjects will be randomly assigned in 1:1:1 ratio to 1 of 3 treatment groups: placebo golimumab, golimumab 50 mg SC inj, or golimumab 100 mg SC inj. At wk 16, subjects in any group who have < 20% improvement from baseline in both swollen and tender joint counts will enter early escape in a double-blinded fashion, which involves an increase in the dose of golimumab or a switch from placebo to golimumab. Randomized, blinded treatment will be maintained through the Wk 24 database lock. At Wk 24, participants will be asked to enter the extension portion of the study, in which all participants will receive golimumab. Subjects will be reimbursed$20 per study visit.
Contact Person: Lindy Kilby (412) 647-2638
Status: Actively Recruiting

 A Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Golimumab, a Fully Human Anti-TNFa Monoclonal Antibody, Administered Subcutaneously, in Methotrexate-naïve Subjects with Active Rheumatoid Arthritis

Lay Summary
This is a study of the safety and reduction of signs and symptoms during treatment with golimumab versus placebo in combination with methotrexate in patients with active rheumatoid arthritis (RA). Golimumab will be given to patients as an injection every 4 weeks (wk). Patients must have active RA and have not previously taken methotrexate or other DMARDs. Patients will be allowed to continue some arthritis medications (some corticosteroids and all NSAIDs) while participating in this study. They will be asked to come to the site for study visits approximately every 4 wk until Wk 52. Patients will have a 1 in 4 chance of being on placebo golimumab during the first 52 wk of the study; however, every patient will receive an active medication for RA (methotrexate and/or golimumab). If they are assigned to placebo golimumab, they will receive active methotrexate. After the first 52 wk of the study, all subjects will be eligible to enter the extension portion of the study that may last up to 5 years. All patients who have at least 1 tender or 1 swollen joint at the Wk 52 visit will receive active golimumab throughout the extension phase. Patients will be trained and allowed to give themselves the injection of study medication during the extension phase and will be asked to return to the site for study visits every 3 months.
Status: Actively Recruiting

Physician Summary
This is a ph. 3, multicenter, randomized, double-blind, placebo-controlled, 4-arm parallel study of multiple SC administrations of golimumab at 2 doses as monotherapy or in combination with methotrexate (MTX), to test the safety and efficacy of golimumab. Subjects will be randomized in a 1:1:1:1 ratio to receive placebo golimumab and active MTX, golimumab 100 mg inj. and pacebo MTX, golimumab 50 mg inj. and active MTX, or golimumab 100 mg inj. and active MTX. At Wk 28, any subject with < 20% improvement from baseline in both swollen and tender joint counts will be eligible for escape therapy, which involves an increase in the dose of golimumab and/or MTX. Randomized, blinded treatment will be maintained through the Wk 52 database lock. At Wk 52, participants will be asked to enter the extension portion of the study, in which all participants will receive golimumab, unless he or she was previously receiveing placebo inj. and does not have any swollen or tender joints. Subjects will be reimbursed $20 per study visit.
Contact Person: Lindy Kilby (412) 647-2638
Status: Actively Recruiting

SCLERODERMA

SCOT – Scleroderma:  Cyclophosphamide or Transplantation
Sponsored by the NIH

Investigator:  Thomas A. Medsger, Jr., MD

The main purpose of this study is to compare the two ways of treating SSc: 1) high-dose immunosuppressive therapy (HDIT) followed by self blood cell transplantation and 2) high-dose intravenous cyclophosphamide (CTX).
One group of study participants will have stem cell transplantation. With this treatment, they will first have hematopoietic stem cells removed from their blood. They then will receive high doses of chemotherapy and radiation to eliminate their developed and presumably abnormal immune system, followed by the reintroduction of the purified stem cells to re-establish their immune system.
The other group of will receive Cyclophosphamide, which is often used to treat autoimmune diseases. However, the dose used in the SCOT study is higher than what doctors typically prescribe, and the length of treatment is longer. In the high-dose pulse CTX arm, 12 monthly pulses of IV CTX are administered.
All participants will be followed for a minimum of 44 months after study entry. Participants will be randomly assigned to one of two arms after eligibility is confirmed.   Visits to a rheumatology center in addition to visits to a regional transplant center will be required, so patients must be able and willing to travel to participate in this trial.  All study participants will have follow-up visits every 4 weeks (or more often if needed) for the first 46 weeks, then at selected months until the end of the study. Currently, 7 transplant centers and 21 rheumatology centers across the U.S., all leaders in the fields of either transplantation or rheumatology, are participating in this research.

Contact Person:  Jennifer Jablon 412-383-8764
Status:  Actively Recruiting

PHAROS - Pulmonary Hypertension Assessment Registry of Scleroderma
Sponsored by the Scleroderma

Foundation Investigator:  Thomas A. Medsger, Jr., MD
Co-Investigators: Robyn Domsic, MD, and Michael Mathier, MD

Pulmonary hypertension (PHT) is increased blood pressure in the arteries supplying the lungs.  In scleroderma patients, this is caused by thickening of these arteries.  It is one of the more serious complications in scleroderma.  Patients with early PHT may have little warning before they develop severe shortness of breath (which is called dyspnea).  The tests doctors commonly prescribe now don’t always catch the early warning signs, but they are the best tests currently available.  This study will follow scleroderma patients who are at risk to develop PHT and those who have been diagnosed with PHT. Investigators will gain a better understanding of who is likely to develop PHT and their response to different therapies.  This study will hopefully lead to earlier treatment or possibly prevention of PHT.  

There are currently 15 major scleroderma research centers in the United States, including the University of Pittsburgh, enrolling adult patients with limited or diffuse systemic sclerosis into the PHAROS Registry.  Patients who consent will provide information from scleroderma-related medical records for the duration of this 5 year study.  They will provide a single blood sample for research. They will complete questionnaires every 6 months (or more frequently if necessary), which can be sent by mail, or can be done on-line.  Medical records will be collected every time patients undergo standard tests and procedures such as pulmonary function tests or echocardiograms.  The information collected by this registry will be used to develop a standard for diagnosing and treating one of the most serious complications people with scleroderma encounter. 

Contact Person:  Jennifer Jablon 412-383-8674
Status: Actively Recruiting

Childhood onset scleroderma is a disease of uncertain cause. It includes systemic sclerosis and localized scleroderma (morphea, linear scleroderma, and eosinophilic fasciitis), and Raynaud phenomenon and a positive ANA test result. Because these conditions are uncommon, it has been difficult to study their clinical and laboratory patterns. The primary purpose for creating the National Registry for Childhood Onset Scleroderma is to gather a large enough number of patients for meaningful research.

The second purpose of this research project is to identify and study specific antibodies that patients with scleroderma often have in their blood. Antibody research may provide clues to this disease and assist physicians in classifying and predicting clinical features and outcome. Antibody studies in adults with systemic sclerosis and localized scleroderma have been important in improving disease classification. It is unknown whether these diseases are different in children compared with adults. It is hoped that the establishment of a large registry of patients with childhood onset scleroderma will stimulate future research on this group of disorders by other investigators.

Inclusion Criteria:
Patients who range in age from birth to 30 years, who have a physician-confirmed diagnosis of either systemic sclerosis or localized scleroderma that began before age 16 are being asked to join the National Registry for Childhood Onset Scleroderma.

Contact person: Jennifer Jablon (800) 603-8960
Status: Actively Recruiting

Systemic Sclerosis Twin Study
Investigator: Carol Feghali-Bostwick, PhD
Co-Investigators: Thomas A Medsger, Jr., MD and Matthew Zirwas, MD
(lay summary)

Lay Summary
This research is being done to determine the role that environmental and inherited factors play in the development of systemic sclerosis (SSc or scleroderma). Several studies suggest the role of environmental factors as 'triggers' of SSc. In addition, familial cases of SSc are rare yet SSc occurs in siblings of SSc subjects more frequently than the average population. The study of twins is the "gold standard" for determining whether a disease is due to shared genes or shared environmental factors. The logic behind the approach is that if inheritance is important in the development of a disease, then one would expect identical twins to both develop the disease since they both inherit the same sets of genes from their parents. If only one twin of an identical twin pair develops the disease, then the disease is not due to inherited genes and is more likely due to environmental factors and/or genetic changes that occur after birth.

Inclusion Criteria: Adult twins, over age 18 (fraternal or identical, male or female), where one or both are affected by systemic sclerosis.

Contact person: Jennifer Jablon (800) 603-8960
Status: Actively Recruiting

Long term bosentan open label extension of the RAPIDS-2 study in systemic sclerosis patients with ischemic digital ulcers
INVESTIGATOR: Thomas A. Medsger, Jr., MD

Lay Summary
This study is an open label trial of bosentan in the treatment of finger ulcers (DUs) due to poor blood supply in persons with systemic sclerosis (SSc). To be eligible for this study, subjects must have completed all visits for the RAPIDS-2 study, which was a double blinded, placebo-controlled trial evaluating the effectiveness of bosentan on healing and the occurrence of new DUs. The specific aim of the current study is to collect long-term data on the efficacy, tolerability and safety of bosentan in the treatment of DUs in SSc patients.

Contact person: Carol Blair, RN (412) 383-8672
Status: Closed

SYSTEMIC LUPUS ERYTHEMATOSUS

University of Pittsburgh Lupus Center of Excellence Patient Registry
The purpose of this registry is to identify patients with lupus who are interested in hearing about current and future research studies in which they may be eligible to participate. As a member of the Registry, you will have the opportunity to learn about the Center's research projects on autoimmune disease and participate in those that may interest you and for which you may be eligible.

Molecular Genetics Analysis of Apolipoprotein H in Systemic Lupus Erythematosus.
This study is a collaborative effort between Dr. Ilyas Kamboh, a molecular geneticist, and Dr. Manzi, a clinician/epidemiologist, to examine how APOH genetic variations predict occurrence of antiphospholipid antibodies and thrombotic events in SLE patients.

Complement Receptor-Ligand Assays for Determination of Diagnosis and Disease Activity in Patients with Inflammatory and Immune-Mediated Disorders, and Hematologic Disorders

Lay Summary
This research study is designed to examine new investigational laboratory markers of activity in inflammatory and autoimmune conditions. Disease activity in lupus has been associated with activation (breakdown) of complement (blood proteins) and deposition of the breakdown proteins on blood cells.
Contact: Margie Ruffing (412) 641-7633
Status: Actively Recruiting

SLICC: the Systemic Lupus International Collaboration Clinics Registry for Atherosclerosis in SLE

Lay Summary
The purpose of this international study involving 10 countries is to determine the frequency of and risk factors for developing vascular disease and neuropsychiatric disease in patients with early lupus (diagnosed with lupus for 18 months or less). To date, over 500 lupus patients have been enrolled.

VARIOUS DISEASES

Banking of Biological Samples and Collection of Clinical Data for Connective Tissue Disease Research

Lay Summary
Connective tissue diseases are chronic diseases that involve damage of connective tissues such as the lining of the joints, blood vessel walls, muscle, skin, and certain internal organs. These diseases are also known as autoimmune diseases because the body's own immune system attacks its own tissues. Treatment has improved over the past 20 years, but there is still much that is not understood about the complications, causes, and treatments of these diseases. The purpose of this project is to set up and maintain a Rheumatology Biological Specimen Bank of blood and tissue samples and a parallel Research Databank of computerized medical information. This is to support research of the CTDs and the factors that contribute to the onset and course of these diseases. Inclusion Criteria: all ages, male or female, diagnosed by a doctor within the Department of Rheumatology with a CTD.
Contact: Mary Lucas (412) 383-8699
Status: Actively Recruiting

UPMC Arthritis Network Registry

Lay Summary
Connective tissue diseases are chronic diseases that involve damage of connective tissues such as the lining of the joints, blood vessel walls, muscle, skin, and certain internal organs. These diseases are also known as autoimmune diseases because the body's own immune system attacks its own tissues. Treatment has improved over the past 20 years, but there is still much that is not understood about the complications, causes, and treatments of these diseases. The purpose of this project is to set up and maintain a Rheumatology Biological Specimen Bank of blood and tissue samples and a parallel Research Databank of computerized medical information. This is to support research of the CTDs and the factors that contribute to the onset and course of these diseases. Inclusion Criteria: all ages, male or female, diagnosed by a doctor within the Department of Rheumatology with a CTD.
Contact: Mary Lucas (412) 383-8699
Status: Actively Recruiting

Basic Research Program

The following descriptions of current biomedical research activities at the University of Pittsburgh has been organized into Research Programs which define groups of investigators with common research interests. All faculty within these Programs are Principal Investigators of independently funded basic and/or clinical scientific projects with specific aims that focus directly upon molecular and cellular mechanisms of arthritis, autoimmune, and musculoskeletal diseases, their treatment, or their prevention. It should be noted that there is extensive collaboration among members of many program areas and that these collaborations extend across the boundaries of basic science and clinical medicine. In fact, one of the strengths of the research base at the University of Pittsburgh is the close working relationships among basic science and clinical faculty.

PROGRAM 1: Development of Gene Transfer To Treat Arthritis, Autoimmune, and Musculoskeletal Disease  

 PROGRAM 2: Cellular and Humoral Immune Responses: Basic Mechanisms and Role in Arthritis, Autoimmune, and Musculoskeletal Diseases

 PROGRAM 3: Cytokines: Basic Immunobiology and Role in Arthritis, Autoimmune and Musculoskeletal Diseases

 PROGRAM 4: Genetics of Arthritis, Autoimmune and Musculoskeletal Diseases

 PROGRAM 5: Evaluation of New Therapeutic Modalities in the Treatment of Arthritis, Autoimmune, and Musculoskeletal Diseases

 PROGRAM 6: Biomechanical and Biochemical Studies of Cartilage and Connective Tissue Matrix

Clincical Research Program

The following descriptions of current clinical research activities at the University of Pittsburgh has been organized into Research Programs which define groups of investigators with common research interests. All faculty within these Programs are Principal Investigators of independently funded clinical scientific projects with specific aims that focus directly upon arthritis, autoimmune, and musculoskeletal diseases. It should be noted that there is extensive collaboration among members of many program areas and that these collaborations extend across the boundaries of basic science and clinical medicine. In fact, one of the strengths of the research base at the University of Pittsburgh is the close working relationships among basic science and clinical faculty.

 PROGRAM 1: Patient Oriented Research and Evaluation of New Therapeutic Modalities in the Treatment of Arthritis, Autoimmune and Musculoskeletal Diseases

This program addresses patient-oriented research on mechanisms of human disease; development of new technologies; clinical trials of novel drugs/therapeutic agents as well as new approaches using conventional immunosuppressive agents.

 PROGRAM 2: Epidemiology of Arthritis, Autoimmune and Musculoskeletal Diseases

Epidemiology of Arthritis, Autoimmune and Musculoskeletal Disease

Program Leader: Jane Cauley, Ph.D., Department of Epidemilogy, Graduate School of Public Health

This program includes both clinical and classical epidemiologits whose overall goal is to improve our understanding of the epidemiology of arthritis, autoimmune and musculoskeletal diseases.  The spectrum of projects ranges from descriptive epidemiologic studies to the identification of etiologic risk factors, or the examination of factors predictive of prognosis and outcome in patients with these diseases.

 PROGRAM 3: Health Services Research - Outcome Assessment in Arthritis, Autoimmune and Musculoskeletal Diseases

Health Services Research -
Outcome Assessment in Arthritis, Autoimmune and Musculoskeletal Diseases

Program Leader: C. Kent Kwoh, M.D., Professor, Division of Rheumatology and Clinical Immunology,  Department of Medicine

This program includes studies whose overall goal is to examine health services utilization, and health care quality; examine a variety of educational and behavioral interventions designed to improve outcomes; and the development of new outcome measures in patients with arthritis, and musculoskeletal diseases.

Patient Registries

The purpose of this registry is to identify patients with lupus who are interested in hearing about current and future research studies in which they may be eligible to participate. As a member of the Registry, you will have the opportunity to learn about the Center's research projects on autoimmune disease and participate in those that may interest you and for which you may be eligible.