Research

Photo of Confocal Microscope

Office of the Clinical Director

Richard Siegel, M.D., Ph.D.
Clinical Director, NIAMS Intramural Research Program
Phone: (301) 496-3374
Fax: (301) 402-0765
E-mail: siegelr@mail.nih.gov

Clinical Programs

The Office of the Clinical Director implements innovative clinical research programs that relate to the broad field of rheumatologic, musculoskeletal and skin disorders. Through specific programs in translational research, rheumatology fellowship training,and health partnership, the Office of the Clinical Director plays an important role in establishing innovative therapeutic paradigms, medical education in the field of rheumatology, and by reaching out to the community to reduce health care disparities and improve the understanding of rheumatic and related diseases.

Translational Research: The Bridge Between Basic Research and Clinical Disease
A goal of clinical investigation is to bridge information gained from laboratory research with that afforded by clinical experience. Carefully designed observational and interventional studies provide opportunities to verify basic biological understanding of disease. These studies then bring back to the laboratory new insight into the biology of the human body.

Rheumatology Fellowship Program
The NIAMS/NIH Rheumatology Fellowship Training Program is dedicated to the clinical and research training of physicians wishing to pursue careers in biomedical or translational research related to the rheumatic diseases. The fellowship program is two years in duration, with extensions available for individuals interested in advanced research training. The program is accredited by the ACGME and graduates are eligible to sit for the certifying examination in the subspecialty of rheumatology.

NIAMS Community Health Center
The NIAMS Community Health Center is a health information and medical center providing health care services to people affected by arthritis, lupus, and other rheumatic diseases. The health center offers patient care with access to a specialist, health information and education programs, and referrals to clinical investigations for the prevention and treatment of rheumatic diseases. The health center is located in Silver Spring.

Current Protocols

The Clinical Program is engaged in several observational studies to understand the natural history of several rheumatic diseases and to test therapeutic interventions. For more information or to access a Protocol, please search the database of clinical studies being conducted at the NIH Clinical Center.
Healthy Volunteers

02-AR-0131: Collection of Blood Components Using Apheresis from Patients with Rheumatic Diseases and Healthy Volunteers. Blood components will be collected using apheresis from normal volunteers and patients with rheumatic diseases. Mononuclear cells and plasma will be used by various investigators for research studies.

03-E-0099: Pathogenic Studies in Families of Twins or Siblings Discordant for Systemic Rheumatic Diseases

11-E-0072: Environmental Risk Factors for the Anti-Synthetase Syndrome, the MYORISK Study

13-E-0015: Environmental Risk Factors for the Development of Myositis in Military Personnel

For the three studies above, healthy volunteers matched to adult and pediatric myositis/autoimmune disease patients will be eligible for enrollment in these studies. Enrollment generally consists of a physician evaluation, patient questionnaires and blood testing. (Contact: Ms. Tasia Long at longtm@niehs.nih.gov).


Systemic Lupus Erythematosus

94-AR-0066: Studies of the Pathogenesis and Natural History of Systemic Lupus Erythematosus (SLE). This study admits patients with systemic lupus erythematosus. The goal is to identify clinical subsets of patient that might aid in understanding progress and determining appropriate therapies.

13-AR-0005: Safety and Tolerability of Omalizumab in Patients with Lupus (STOP LUPUS). This study will target a pathway (discovered at NIAMS) of basophil activation by IgE ds-DNA autoantibodies, found to be significant in the pathogenesis of SLE in a subset of patients. This study will examine the safety of anti-IgE antibody (omalizumab) in patients with mild-moderate lupus.

03-E-0099: Pathogenic Studies in Families of Twins or Siblings Discordant for Systemic Rheumatic Diseases. Patients diagnosed with adult or juvenile systemic lupus erythematosus within the past four years and their healthy same gender-siblings are part of a study to evaluate environmental and genetic risk factors for systemic autoimmune diseases. When available, parents also enroll. The study involves patient questionnaires, blood testing, and a physician evaluation. Further clinical evaluation may be performed as indicated when enrolling at the NIH Clinical Center. Patients may enroll from the NIH Clinical Center in Bethesda or through their local physicianís office. (Contact: Adult patient referrals: Dr. Adam Schiffenbauer at schiffenbauera2@niehs.nih.gov); Pediatric patient referrals: Dr. Lisa Rider at riderl@mail.nih.gov).


Arthritis

00-AR-0222: Studies of the Pathogenesis and Natural History of Arthritis and Related Conditions. This study admits patients with rheumatoid arthritis or juvenile rheumatoid arthritis. The goal is to understand the progression of the disease and the associated medical conditions.

13-AR-0056: Stopping Anti-TNF Agents in Rheumatoid Arthritis (STARA) Trial Stopping TNF-alpha agents in Rheumatoid Arthritis . The goal of this randomized clinical trial is to test if patients with rheumatoid arthritis in remission while taking TNF-alpha inhibitors can remain in remission after withdrawal of these medications, and to determine predictors of relapse.

03-E-0099: Pathogenic Studies in Families of Twins or Siblings Discordant for Systemic Rheumatic Diseases. Patients diagnosed with adult or juvenile systemic lupus erythematosus within the past four years and their healthy same gender-siblings are part of a study to evaluate environmental and genetic risk factors for systemic autoimmune diseases. When available, parents also enroll. The study involves patient questionnaires, blood testing, and a physician evaluation. Further clinical evaluation may be performed as indicated when enrolling at the NIH Clinical Center. Patients may enroll from the NIH Clinical Center in Bethesda or through their local physicianís office. (Contact: Adult patient referrals: Dr. Adam Schiffenbauer at schiffenbauera2@niehs.nih.gov; Pediatric patient referrals: Dr. Lisa Rider at riderl@mail.nih.gov).


Periodic Fever Syndromes and Other Autoinflammatory Diseases

03-AR-0298: A Pilot Study with the IL-1 Receptor Antagonist Anakinra/Kineret in Patients with Neonatal Onset Multisystem Inflammatory Disease (NOMID/CINCA Syndrome). This is a pilot study using the IL-1 receptor antagonist anakinra to treat children with Neonatal Onset Multisystem Inflammatory Disease (NOMID), also known as chronic infantile neurological, cutaneous and articular (CINCA) syndrome.

03-AR-0173: Studies of the Natural History, Pathogenesis, and Outcome of Autoinflammatory Diseases (NOMID/CAPS, DIRA, CANDLE, CRMO, Still's Disease, Behçet's Disease, and other Undifferentiated Autoinflammatory Diseases). This study will examine and test patients with neonatal onset multi-system inflammatory disease (NOMID) to learn more about the cause and course of the disease. It will study the disease signs and symptoms and the possible role of a gene called CIAS1, and it will develop a database to gather information on patients with NOMID in the United States and around the world. It will also serve as a screening protocol to offer eligible patients participation in a treatment protocol, if an appropriate one is available.

11-AR-0241: A Pilot Study of Anakinra in Behçet's Disease (BD). This exploratory study aims to examine the utility of anakinra in the treatment of adult subjects with ehçet's Disease, a disease which shows similarities to the known anakinra-responsive autoinflammatory disorders, familial cold autoinflammatory syndrome (FCAS) and Muckle-Wells Syndrome. Anakinra is a recombinant form of the human interleukin-1 receptor antagonist that has been studied in RA and the autoinflammatory disorders. This pilot study is designed to address: 1) the utility of anakinra in the treatment of BD; 2) the effect of anakinra on laboratory biomarkers in BD; and 3) the safety of anakinra in individuals with Behçet's Disease.

12-AR-8001: Compassionate Use Treatment Protocol 14V-MC-JAGA Treatment of Autoinflammatory Syndromes Expected to Benefit from JAK 1/2 Inhibition. The purpose of this open-label, compassionate-use-treatment protocol is to provide baricitinib to patients with autoinflammatory syndromes who are not responsive to biologic therapies, require treatment with high doses of steroids to control systemic signs and symptoms of their syndrome, and who are eligible for treatment under this protocol. CANDLE syndrome (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature) is one of the syndromes being treated under this protocol.

13-AR-0086: A Pilot Open-Label Study of Rilonacept (Arcalyst) in the Deficiency of the Interleukin-1 Receptor Antagonist (DIRA). There is growing genetic and clinical evidence that specific cytokine pathways are dysregulated in autoinflammatory diseases. One example is DIRA (Deficiency of the IL-1 receptor antagonist) caused by mutations affecting the IL-1-receptor antagonist gene (IL1RN). This disorder responds with complete resolution of the inflammatory response to treatment with the short acting IL-1 blocking agent anakinra. This study aims to examine the utility of the long acting IL-1 inhibitor rilonacept. This study is designed to address: 1) the utility and dosage of rilonacept needed to achieve inflammatory remission in children with DIRA who have shown a response to treatment with anakinra; and 2) to evaluate the safety and pharmacokinetics in young children on rilonacept.


Myositis

91-AR-0196: Studies of the Natural History and Pathogenesis of Polymyositis, Dermatomyositis and Related Diseases. This study admits patient with polymyositis, dermatomyositis and other muscle diseases. The goal is to understand the progression of these diseases.

03-E-0099: Pathogenic Studies in Families of Twins or Siblings Discordant for Systemic Rheumatic Diseases. Patients diagnosed with adult or juvenile systemic lupus erythematosus within the past four years and their healthy same gender-siblings are part of a study to evaluate environmental and genetic risk factors for systemic autoimmune diseases. When available, parents also enroll. The study involves patient questionnaires, blood testing, and a physician evaluation. Further clinical evaluation may be performed as indicated when enrolling at the NIH Clinical Center. Patients may enroll from the NIH Clinical Center in Bethesda or through their local physicianís office. (Contact: Adult patient referrals: Dr. Adam Schiffenbauer at schiffenbauera2@niehs.nih.gov; Pediatric patient referrals: Dr. Lisa Rider at riderl@mail.nih.gov).

11-E-0072: Environmental Risk Factors for the Anti-Synthetase Syndrome, the MYORISK Study. Adults and children with dermatomyositis or polymyositis who are within one year of diagnosis are potentially eligible for this study.  The goal is to evaluate environmental factors that may be important to illness onset in myositis patients with certain autoantibodies (such as Jo1) compared to those without these autoantibodies and to healthy control subjects. The study involves patient questionnaires, blood testing, a vacuum dust sample, and a physician evaluation. Further evaluation, including heart and lung studies and imaging, may be performed as clinically indicated when enrolling at the NIH Clinical Center. Patients may enroll from the NIH Clinical Center in Bethesda, through another participating center, or through their local physician’s office. (Contact: study coordinator Ms. Tasia Long at longtm@niehs.nih.gov).

13-E-0015: Environmental Risk Factors for the Development of Myositis in Military Personnel. Patients who developed myositis while serving on active duty in the military will be compared withmilitary personnel who have not been diagnosed with an autoimmune disease or chronic muscle disease. The study will consist of a physician evaluation, as well as patient questionnaires and blood samples.A few patients will also contribute a muscle biopsy sample, if clinically indicated to perform this test. Patients may enroll from the NIH Clinical Center in Bethesda, through a participating military hospital or VA medical center, or through their local physician’s office. (Contact: study coordinator Mr. James Ridley: james.ridley@nih.gov).

94-E-0165: Studies in the Natural History & Pathogenesis of Childhood-Onset and Adult-Onset Idiopathic Inflammatory Myopathies. This study enrolls patients with adult and juvenile dermatomyositis and polymyositis primarily. Patients generally only enroll if enrolling in another NIEHS study protocol. This study provides a thorough disease evaluation, including blood testing and imaging studies. Goals of the study include examination of genetic and environmental risk factors for myositis and natural history of the disease. (Contact: Adult patient referrals: Dr. Adam Schiffenbauer at schiffenbauera2@niehs.nih.gov; Pediatric patient referrals: Dr. Lisa Rider at riderl@mail.nih.gov).


Ankylosing Spondylitis and Spondylarthritis

04-AR-0205: Progression of Spinal Fusion in Ankylosing Spondylitis. This pilot study seeks to determine if a CT (computerized tomography) scan can measure changes in fusion of the spine better than regular X-rays.

03-AR-0131: Genetic Determinants of Ankylosing Spondylitis Severity - Longitudinal Study. This study will explore how genes may influence the severity of ankylosing spondylitis, a form of arthritis that affects the spine.

11-AR-0223 Studies on the Natural History and Pathogenesis of Spondyloarthritis (SpA). The National Institute of Arthritis and Musculoskeletal and Skin Diseases is conducting a study to learn more about the early signs and symptoms of SpA. The goal of this study is to follow the activity and progression of SpA. Patients will be screened with a comprehensive individual history and a physical examination that includes a detailed musculoskeletal exam. Participants of any age with a diagnosis of SpA may be eligible. This protocol will serve as a screening protocol for a future SpA treatment protocol.


Immunodeficiency

99-AR-0004: Molecular Basis of Primary Immunodeficiencies. This study is to identify the genetic basis for immunodeficiencies in patients for whom the genetic basis is unknown. The goal is to identify genes important in the immune system regulation which are mutated or defective in patient with primary immunodeficiencies.


Health Disparities

01-AR-0227: Natural History of Rheumatoid Disease in Minority Communities. This study is designed to address the differences in clinical manifestations and severity of rheumatologic disease in African-Americans and Hispanic individuals.


Osteoporosis

11-AR-0156 : Bisphosphonate Users Radiographic Characteristics of the Hip (BURCH). Bisphosphonates reduce the incidence of classical forms of osteoporotic fractures. However, they may be linked to atypical subtrochanteric fractures after long-term use. The goals of this study are to prospectively assess and characterize features of atypical hip fractures in users of bisphosphonates.


Scleroderma

03-E-0099: Pathogenic Studies in Families of Twins or Siblings Discordant for Systemic Rheumatic Diseases. Patients diagnosed with adult or juvenile systemic lupus erythematosus within the past four years and their healthy same gender-siblings are part of a study to evaluate environmental and genetic risk factors for systemic autoimmune diseases. When available, parents also enroll. The study involves patient questionnaires, blood testing, and a physician evaluation. Further clinical evaluation may be performed as indicated when enrolling at the NIH Clinical Center. Patients may enroll from the NIH Clinical Center in Bethesda or through their local physicianís office. (Contact: Adult patient referrals: Dr. Adam Schiffenbauer at schiffenbauera2@niehs.nih.gov; Pediatric patient referrals: Dr. Lisa Rider at riderl@mail.nih.gov).

Selected Publications

Nowak M, Carrasquillo JA, Yarboro CH, Bacharach SL, Whatley M, Valencia X, Takada K, Brust DG, Illei GG. A pilot study of the use of 2-[18F]-fluoro-2-deoxy-D-glucose-positron emission tomography to assess the distribution of activated lymphocytes in patients with systemic lupus erythematosus. Arthritis Rheum. 2004; 50(4): 1233-8. PubMed Icon

Illei GG, Takada K, Parkin D, Austin HA, Crane M, Yarboro CH, Vaughan EM, Kuroiwa T, Danning CL, Pando J, Steinberg AD, Gourley MF, Klippel JH, Balow JE, Boumpas DT. Renal flares are common in patients with severe proliferative lupus nephritis treated with pulse immunosuppressive therapy: long-term followup of a cohort of 145 patients participating in randomized controlled studies. Arthritis Rheum. 2002; 46(4): 995-1002. PubMed Icon

Kastner DL, O'Shea JJ. A fever gene comes in from the cold. Nat Genet. 2001; 29(3): 241-2. PubMed Icon

Evans JT, Cravens P, Gatlin J, Kelly PF, Lipsky PE, Garcia JV. Pre-clinical evaluation of an in vitro selection protocol for the enrichment of transduced CD34+ cell-derived human dendritic cells. Gene Ther. 2001 Sep; 8(18): 1427-35. PubMed Icon

Hull KM, Griffith L, Kuncl RW, Wigley FM. A deceptive case of amyloid myopathy: clinical and magnetic resonance imaging features. Arthritis Rheum. 2001; 44(8):1954-8. PubMed Icon

See extended list of publications

 

Updated December 19, 2013