Study of Families With Twins or Siblings Discordant for Rheumatic Disorders
|First Received Date ICMJE||February 15, 2003|
|Last Updated Date||June 17, 2014|
|Start Date ICMJE||February 2003|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||Physician Global Assesment Questionnaire [ Time Frame: Time of enrollment ] [ Designated as safety issue: No ]|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00055055 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Study of Families With Twins or Siblings Discordant for Rheumatic Disorders|
|Official Title ICMJE||Pathogenic Studies In Families With Twins Or Siblings Discordant For Systemic Rheumatic Disorders|
This study will examine families in which one sibling of a sibling pair, or twin pair, has developed a systemic rheumatic disease and one has not, to see if and how the two differ in the following:
Families in which one sibling has developed a systemic rheumatic disease, rheumatoid arthritis, systemic lupus erythematosus, scleroderma, dermatomyositis, or myositis, and the other has not, are eligible for this study. The siblings may or may not be twins, but must be of the same gender and be within a 3-year age difference. Biological parents, or, in some cases, children, will also be included in the study. Normal, healthy volunteers will serve as control subjects.
Participants will undergo some or all of the following tests and procedures:
Participants may be asked for permission to have some of their blood and urine samples stored and to obtain previously collected blood or tissue biopsy specimens that are no longer needed for clinical care, for research purposes. They may also be asked to give additional blood or urine samples.
Participants will be followed every year for 5 years (either in person or by questionnaire) to evaluate any changes in their condition. The final 5-year evaluation will repeat some of the questionnaires and procedures described above.
Most autoimmune diseases are thought to develop as a result of chronic immune activation and dysregulation after selected environmental exposures in genetically susceptible individuals. Current evidence suggests that the adult and juvenile forms of systemic rheumatic disorders -- defined here as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and idiopathic inflammatory myopathies (IIM) -- share many common clinical manifestations, immune responses, genetic, hormonal and environmental risk factors, and possible pathogeneses. Conversely, other studies imply that each rheumatic disease, as currently defined, may be composed of more homogeneous subgroups, known as elemental disorders, with different pathogeneses. This protocol will explore pathogenic mechanisms for systemic rheumatic disorders and possible elemental disorders through the evaluation of families with monozygotic or dizygotic twins or other siblings discordant for systemic rheumatic disorders (twin-sib pairs). Parents, normal volunteers and offspring of microchimeric female twin-sibs will also be evaluated as needed for the experimental designs of each portion of the protocol. A clinical evaluation, using standardized physician and patient clinical and environmental exposure questionnaires, and specimen collections 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. 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. Hypothesis-testing studies will assess differences in peripheral blood cell gene activation/suppression, levels and types of microchimerism between affected and unaffected individuals, selected genetic risk factors for these disorders and occupational and hormonal exposures hypothesized 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 better understand 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.
|Study Type ICMJE||Observational|
|Study Design ICMJE||Time Perspective: Prospective|
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Intervention ICMJE||Not Provided|
|Study Group/Cohort (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||1400|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
The minimum inclusion criteria needed for enrollment are a twin pair or sibling pair, as defined by an eligible proband and his/her eligible twin or sibling, willing and able to give informed consent, to enroll in the study, to complete the questionnaires and to donate blood and urine samples (in case of children, parent/legal guardian must also be willing and able to provide informed consent).
Proband inclusion criteria:
-Children (< 18 years of age) or adults (18 or more years of age) require a diagnosis of a systemic rheumatic disorder (by American College of Rheumatology (ACR) or other criteria for the adult or juvenile forms of RA, SLE, SSc, or IIM (per (92;93). Regarding the childhood-onset diseases: JRA will be defined by age of onset < 17 years of age; for other diseases age of onset will be < 18 years. Probands will be diagnosed within 4 years of enrollment in the study, with at least one twin or other sibling of the same gender within 4 years of age and without a recognized systemic rheumatic disorder or other autoimmune disease available for study.
Twin-sibling inclusion criteria:
-Children or adults who are twins or other siblings of a proband sharing the same biological parents, but without a recognized systemic rheumatic or autoimmune disorder, of the same gender and within 4 years of age of the proband. If monozygotic twins are enrolled from a family, another unaffected non-twin sibling sharing the same biological parents will be enrolled for each proband if available to allow for log-linear genetic analyses. All probands and unaffected siblings need to be at least one year of age at the time of autoimmune disease diagnosis. In the case of triplets or greater multiples, all such siblings are eligible for enrollment.
Parent inclusion criteria:
-Individuals who are the genetic father and mother of the proband and twin-sib. Both parents will be enrolled whenever possible.
Normal volunteer inclusion criteria:
-Healthy controls, recruited in part via the NIH Normal Volunteers program, and age- (within 5 years in adults and 4 years in children), gender- and race-matched to a subset of probands as controls needed for specific studies. Normal volunteers should be in good health, without a recognized systemic rheumatic disorder or other autoimmune disease, and should not be taking anti-inflammatory medicines, including nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids.
Offspring of microchimeric women criteria:
-Biological offspring of women who are probands and are found to be microchimeric. These offspring will be enrolled as normal volunteers in an attempt to confirm the source of their mothers microchimerism.
For all subjects:
-Ability of the subject or parents/legal guardians to provide informed consent to all aspects of the study after full protocol information is provided.
Exclusion criteria for all protocol subjects:
Exclusion criteria for twin-sibs:
-Not sharing the same biological parents (being half-brothers or half-sisters). Known criteria for systemic rheumatic disease or autoimmune disease (for example: RA/JRA, SLE/JSLE, SSc/JSSc, IIM/JIIM, Type 1 diabetes, Psoriasis, Still s disease/systemic-onset or pauciarticular JRA, Celiac sprue, Autoimmune thyroid disease, Idiopathic Thrombocytopenia Purpura, Multiple sclerosis, Myasthenia gravis, Systemic vasculitis or Vitiligo).
Exclusion criteria for normal volunteers:
-Recognized systemic rheumatic disorder or other autoimmune disease, history of cancer or taking anti-inflammatory medicines, including nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids, severe trauma or vaccinations within 8 weeks, HIV+.
|Accepts Healthy Volunteers||Yes|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT00055055|
|Other Study ID Numbers ICMJE||030099, 03-E-0099|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||National Institutes of Health Clinical Center (CC) ( National Institute of Environmental Health Sciences (NIEHS) )|
|Study Sponsor ICMJE||National Institute of Environmental Health Sciences (NIEHS)|
|Collaborators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||May 2014|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP