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Pathogenic Studies in Families with Twins or Siblings Discordant for Systemic Rheumatic Disorders

TwinSibs Study – 03-E-0099

Study Design
Current evidence suggests that the adult and juvenile forms of systemic rheumatic disorders -- defined here as Rheumatoid Arthritis, Systemic Lupus Erythematosus (Lupus), Systemic Sclerosis (Scleroderma), and Idiopathic Inflammatory Myopathies (Myositis) -- share many common clinical manifestations, immune responses, genetic, hormonal and environmental risk factors, and possible causes. This protocol will explore the risk factors for systemic rheumatic disorders through the evaluation of families with monozygotic (identical) or dizygotic (fraternal) twins or other brothers or sisters (siblings) discordant for systemic rheumatic disorders (twin-sib pairs). Parents, normal volunteers will also be evaluated as needed for the experimental designs of each portion of the protocol.

 

A clinical evaluation, using physician and patient clinical and environmental exposure questionnaires, and specimen collection from 400 twin-sib pairs discordant for systemic rheumatic disorders, will be performed to confirm diagnoses, document medical histories and assess possible risk factors implicated in the development of autoimmunity.

 

Purpose
This study will evaluate children, who will make up 25-50% of the twin-sib pairs, and adults in similar ways to attempt to understand possible similarities and differences in pathogeneses of systemic rheumatic disorders based upon age of onset. Studies will assess differences in peripheral blood cell gene activation/suppression, genetic risk factors for these disorders and occupational and hormonal exposures thought to be potential risk factors for these diseases. Exploratory studies will be conducted to begin to assess other environmental risk factors for systemic rheumatic disorders and to gain a better understanding of associations among phenotypes and genotypes. Biologic specimens -- including blood, urine, and other clinical specimens or biopsies no longer necessary for clinical care -- will be collected for directed biomarker assays and the development of repositories for future research.

 

Subjects
Subjects with systemic rheumatic diseases (Rheumatoid arthritis/Polyarticular juvenile idiopathic arthritis (JIA), Lupus, Scleroderma, or Myositis) and unaffected twins and other siblings, their parents, and normal volunteers

 

Number of Subjects
400 individuals with systemic rheumatic disorders
400-500 same sex brothers or sisters (twins or siblings) of the persons with systemic rheumatic disorders
400-600 parents, 100 normal volunteers

 

Overview of the Study and Evaluations
Adults or children are eligible to participate if they have been diagnosed with a systemic rheumatic disease above within 47 months and they have a twin or same sex brother or sister who is well and within 47 months of age. Parents and matched normal volunteers will also be asked to participate. This is a blood, urine, and data collection study. A single visit and evaluation is all that is required.

 

Evaluations include history and physical examinations and a number of blood tests. Blood and urine will also be collected for storage.

 

Recruitment Detail
Gender: Male & Female
Ages: Children and adults

Population Exclusion(s)
None

Eligibility Criteria

  1. Inclusion Criteria
    Adults or children are eligible to participate if they have been diagnosed with a systemic rheumatic disease (Rheumatoid arthritis/Polyarticular juvenile idiopathic arthritis (JIA), Lupus, Scleroderma, or Myositis) within 47 months and they have a twin or same sex sibling who is well and within 47 months of age
  2. Exclusion Criteria
    1. Exclusion criteria for persons affected by a systemic autoimmune disease
      1. Active infections requiring therapy or alteration in daily occupation or antibiotics, severe trauma or vaccinations within 8 weeks of enrollment
      2. Still's disease/systemic-onset or Polyarticular Juvenile Idiopathic Arthritis
    2. Exclusion criteria for twin-sibs
      1. Not sharing the same biological parents (being half-brothers or half-sisters)
      2. Known criteria for systemic rheumatic disease or autoimmune disease in the unaffected twin or sibling: (for example: Rheumatoid arthritis, Juvenile rheumatoid arthritis, Lupus, Scleroderma, Myositis, Type 1 Diabetes, Psoriasis, Still's Disease, Celiac Sprue, Autoimmune Thyroid Disease, Idiopathic Thrombocytopenia Purpura, Multiple Sclerosis, Myasthenia Gravis, Systemic Vasculitis or Vitiligo)
    3. Exclusion criteria for normal volunteers
      1. Recognized systemic rheumatic disorder or other autoimmune disease
      2. History of cancer or taking chronic anti-inflammatory medicines, including nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids
      3. Vaccinations within 8 weeks
      4. HIV+

 

Treatment Intervention
None

 

Additional information is available in the representative protocol consent and assent below:

  1. Consent for patients enrolling at the NIH Clinical Center(67KB)
  2. Assent for minor patient or sibling(24KB)

 

More Information may also be found at the website below:
http://clinicaltrials.gov/ct2/show/NCT00055055?term=myositis&rank=19 

 

Study Sites
Subjects may be enrolled at the NIH Clinical Center, 9000 Rockville Pike, Bethesda, MD, 20892, or at the NIEHS Clinical Research Unit, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, or in your local doctor's office.

 

Study Contacts

Adult Subjects

Irene Z. Whitt, M.D.
NIH, Warren Grant Magnuson Clinical Center
10 Center Drive, Bldg. 10, Room 6C432D, MSC 1627
Bethesda, Maryland 20892-1627
Tel (301) 451-6270,1-888-271-3207
Fax (301) 451-5717
Irene.whitt@nih.gov
Frederick W. Miller, M.D., Ph.D.
Principal Investigator
Hatfield Clinical Research Center, NIH
10 Center Drive, Bldg. 10, Room 4-2352, MSC 1301
Bethesda, Maryland 20892-1301
Tel (301) 451-6273, 1-888-271-3207
Fax (301) 451-5585
millerf@mail.nih.gov

 
Pediatric Subjects

Lisa G. Rider, M.D.
Deputy Chief
Environmental Autoimmunity Group
Hatfield Clinical Research Center, NIH
10 Center Drive, Bldg. 10, Room 4-2352, MSC 1301
Bethesda, Maryland 20892-1301
Tel (301) 451-6272,1-888-271-3207
Fax (301) 451-5588
riderl@mail.nih.gov
Referral/Patient Recruitment
Warren Grant Magnuson Clinical Center
National Institutes of Health
Bethesda, Maryland 20892-2655
Tel 1-800-411-1222, TTY 1-866-411-
Fax (301) 451-5588
prpl@mail.cc.nih.gov

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