Familial Mediterranean Fever and Related Disorders: Genetics and Disease Characteristics
- Conditions
- FeverPeriodic FeverFamilial Mediterranean Fever (FMF)AutoinflammationGenetic DiseasesROSAHALPK1
- Registration Number
- NCT00001373
- Lead Sponsor
- National Human Genome Research Institute (NHGRI)
- Brief Summary
This study is designed to explore the genetics and pathophysiology of diseases presenting with intermittent fever, including familial Mediterranean fever, TRAPS, hyper-IgD syndrome, and related diseases.
The following individuals may be eligible for this natural history study: 1) patients with known or suspected familial Mediterranean fever, TRAPS, hyper-IgD syndrome or related disorders; 2) relatives of these patients; 3) healthy, normal volunteers 7 years of age or older.
Patients will undergo a medical and family history, physical examination, blood and urine tests. Additional tests and procedures may include the following:
1. X-rays
2. Consultations with specialists
3. DNA sample collection (blood or saliva sample) for genetic studies. These might include studies of specific genes, or more complete sequencing of the genome.
4. Additional blood samples a maximum of 1 pint (450 ml) during a 6-week period for studies of white cell adhesion (stickiness)
5. Leukapheresis for collecting larger amounts of white cells for study. For this procedure, whole blood is collected through a needle in an arm vein. The blood flows through a machine that separates it into its components. The white cells are removed and the rest of the blood is returned to the body through another needle in the other arm.
Patients may be followed approximately every 6 months to monitor symptoms, adjust medicine dosages, and undergo routine blood and urine tests. They will receive genetic counseling by the study team on the risk of having affected children and be advised of treatment options.
Participating relatives will undergo a medical and family history, possibly with a review of medical records, physical examination, blood and urine tests. Additional procedures may include a 24-hour urine collection, X-rays, and consultations with medical specialists. A DNA sample (blood or saliva) will also be collected for genetic studies. Additional blood samples of no more than 550 mL during an 8-week period may be requested for studies of white cell adhesion (stickiness).
Relatives who have familial Mediterranean fever, TRAPS, or hyper-IgD syndrome will receive the same follow-up and counseling as described for patients above.
Normal volunteers and patients with gout will have a brief health interview and check of vital signs (blood pressure and pulse) and will provide a blood sample (up to 90 ml, or 6 tablespoons). Additional blood samples of no more than 1 pint over a 6-week period may be requested in the future.
- Detailed Description
Study Description
This is an exploratory natural history protocol that will enroll patients with known or as yet undiagnosed disorders of inflammation. Blood, saliva, or buccal samples will be collected for genetic analysis, blood samples will be obtained for immunologic and other functional studies, a small number of subjects may undergo skin biopsy, leukapheresis, or bone marrow aspiration and biopsy, and some patients will be provided standard medical care follow up, with retrospective analysis of the clinical data gathered during follow up.
Objectives
Primary Objective: To discover the genetic basis of human disorders of inflammation.
Secondary Objective: To enumerate immunologic features and genotype-phenotype associations in specific inflammatory diseases.
Tertiary Objectives: To describe the clinical features of poorly characterized or newly defined disorders of inflammation, through the retrospective chart review of standard medical practice follow up and through the enrollment of selected subjects in separate, disease-specific protocols.
Endpoints
Primary Endpoints: The discovery of rare, high-penetrance genetic variants and common, low-penetrance genetic variants conferring susceptibility to inflammatory disease; the discovery of structural genomic variants (insertions, deletions, inversions, translocations, etc.) that cause human inflammatory disease; the discovery of common, low-penetrance germline variants that confer susceptibility to human inflammatory disease; and the discovery of somatic mutations that give rise to human inflammatory disease.
Secondary Endpoint: The description of immune cell populations, inflammatory mediators, gene expression profiling, epigenetic features, and ex vivo functional assays of leukocytes from subjects with specific inflammatory diseases.
Tertiary Endpoints: Given the wide range of inflammatory diseases, the endpoints will be formulated for specific conditions based on the clinical features of that condition.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 5000
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Genetic linkage in autoinflammatory dise annually discovery of genetic associations to autoinflammatory disorders
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (5)
Childrens National Medical Center
🇺🇸Washington, District of Columbia, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Walter Reed National Medical Center
🇺🇸Bethesda, Maryland, United States
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States
University of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States