Familial Mediterranean Fever and Related Disorders: Genetics and Disease Characteristics
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00001373|
Recruitment Status : Recruiting
First Posted : November 4, 1999
Last Update Posted : March 1, 2021
|First Submitted Date||November 3, 1999|
|First Posted Date||November 4, 1999|
|Last Update Posted Date||March 1, 2021|
|Actual Study Start Date||March 10, 1994|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures
||Genetic linkage in autoinflammatory dise [ Time Frame: annually ]
discovery of genetic associations to autoinflammatory disorders
|Original Primary Outcome Measures||Not Provided|
|Current Secondary Outcome Measures||Not Provided|
|Original Secondary Outcome Measures||Not Provided|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title||Familial Mediterranean Fever and Related Disorders: Genetics and Disease Characteristics|
|Official Title||An Exploratory Study of the Genetics, Pathophysiology, and Natural History of Autoinflammatory Diseases|
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 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:
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||This is an exploratory natural history protocol that enrolls 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 subjects will be provided standard medical care follow up, with retrospective analysis of the clinical data gathered during follow up. The primary objective is to discover the genetic basis of human disorders of inflammation. The secondary objective is to enumerate immunologic features and genotype-phenotype associations in specific autoinflammatory diseases. The tertiary objective is to describe the clinical features of poorly characterized or newly defined disorders of inflammation. This protocol provided clinical support for the identification of the gene mutated in familial Mediterranean fever (FMF), the discovery of the TNF receptor-associated periodic syndrome (TRAPS), the identification of NLRP3 mutations in the neonatal-onset multisystem inflammatory disease (NOMID), the discovery of the deficiency of the IL-1 receptor antagonist (DIRA), and the proposal of the now widely accepted concept of autoinflammatory disease. During the last decade the protocol has provided the clinical foundation for the discovery of ten more monogenic autoinflammatory diseases, seven of which were previously unrecognized as distinct diseases. The protocol has also permitted numerous studies delineating the mechanisms of autoinflammation and its connections with the human innate immune system. The work catalyzed by this protocol has provided the conceptual basis for a number of targeted therapies. During the next decade the objective will be to utilize cutting edge genomic technologies to further advance discovery.|
|Study Design||Observational Model: Cohort
Time Perspective: Prospective
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Non-Probability Sample|
|Study Population||Patients with autoinflammatory disorders and unaffected family members, and healthy volunteers.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Study Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
There are three populations that will be included in this study: subjects with known or suspected autoinflammatory diseases, family members of subjects with known or suspected autoinflammatory diseases, and healthy controls. In order to be eligible to participate in this study as a subject with known or suspected autoinflammatory disease, an individual must meet all of the following criteria:
In order to be eligible to participate in this study as a family member of a subject with known or suspected autoinflammatory disease, an individual must meet all of the following criteria:
In order to be eligible to participate in this study as a healthy volunteer, an individual must meet all of the following criteria:
For any of the three categories of subjects, an individual will be excluded from participation in this study if he or she has a medical condition that would, in the opinion of the investigators, confuse the interpretation of the study.
|Ages||1 Month and older (Child, Adult, Older Adult)|
|Accepts Healthy Volunteers||Yes|
|Listed Location Countries||United States|
|Removed Location Countries|
|Other Study ID Numbers||940105
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) )|
|Study Sponsor||National Human Genome Research Institute (NHGRI)|
|PRS Account||National Institutes of Health Clinical Center (CC)|
|Verification Date||February 25, 2021|