Familial Mediterranean Fever (FMF)NCT00001373
Familial Mediterranean Fever and Related Disorders: Genetics and Disease Characteristics
An observational study of Familial Mediterranean Fever (FMF) and Autoinflammation, run by National Human Genome Research Institute (NHGRI) at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 months to 115 yearsHealthy volunteers can take part
- Conditions the study is for
- Familial Mediterranean Fever (FMF), Autoinflammation, Periodic Fever
- How many people
- 5,000 participants
- Where
- 5 sitesUnited States
- Study dates
- 10 Mar 1994to not given
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 months to 115 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Patients with autoinflammatory disorders and unaffected family members, and healthy volunteers.
Who may be able to join
- 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. Persons interested in participation may be given a screening questionnaire to determine eligibility. Questions in the screening questionnaire are important to help us determine if subjects have known autoinflammatory diseases, or if there is a high clinical suspicion of autoinflammatory disease.
- 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:
- Stated willingness to participate in study procedures (which at the very least includes providing a mail-in sample for genetic analysis);
- Regardless of gender, at least one month of age;
- A medical history that, in the expert opinion of the study team, is consistent with the possibility of autoinflammatory disease; and
- Ability of the subject, parents (in the case of children), or Legally Authorized Representative to understand and the willingness to sign a written informed consent document.
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- 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:
- Stated willingness to participate in study procedures (which at the very least includes providing a mail-in sample for genetic analysis);
- Regardless of gender, at least one month of age;
- Relationship, either by blood or marriage, to an individual enrolled or about to be enrolled in the study with known or suspected autoinflammatory disease;
- Likelihood, in the expert opinion of the study team, that analysis of a sample from the individual would advance genetic or functional analysis of the affected relative's possible autoinflammatory condition; and
- Ability of the subject, parents (in the case of children), or Legally Authorized Representative to understand and the willingness to sign a written informed consent document.
- In order to be eligible to participate in this study as a healthy volunteer, an individual must meet all of the following criteria:
- Stated willingness to participate in study procedures for healthy volunteers;
- Regardless of gender, at least one year old, and not pregnant (by history of a missed menstrual period);
- Likelihood, in the expert opinion of the study team, that a sample from the individual would advance the functional analysis of an autoinflammatory condition under study; and
- Ability of the subject or parents (in the case of children) to understand and the willingness to sign a written informed consent document.
Who cannot join
- 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.
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
United States5 sites, 2 recruiting
- Completed
Johns Hopkins University
Baltimore, Maryland, 21205
- Completed
Walter Reed National Medical Center
Bethesda, Maryland, 20301
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
NIH Clinical Center Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
- Not yet recruiting
University of Pittsburgh
Pittsburgh, Pennsylvania, 15261
Daniella Schwartz, 412-648-1587, Daniella.Schwartz@pitt.edu
- Completed
Childrens National Medical Center
Washington D.C., District of Columbia, 20010
About this study
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 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.
Read more
Patients will undergo a medical and family history, physical examination, blood and urine tests. Additional tests and procedures may include the following:
- X-rays
- Consultations with specialists
- DNA sample collection (blood or saliva sample) for genetic studies. These might include studies of specific genes, or more complete sequencing of the genome.
- Additional blood samples a maximum of 1 pint (450 ml) during a 6-week period for studies of white cell adhesion (stickiness)
- 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.
Read the 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.
- Conditions
- Familial Mediterranean Fever (FMF), Autoinflammation, Periodic Fever, Fever, Genetic Diseases, ROSAH
- Keywords
- Splenomegaly, Retinal Dystrophy, Periodic Fever, Optic Nerve Edema, HEADACHE, Genetics, Familial Mediterranean, Autoinflammation, Anhidrosis, Alpha-Kinase 1
- Medical subject headings
- Familial Mediterranean Fever, Hereditary Autoinflammatory Diseases, Fever, Genetic Diseases, Inborn, Splenomegaly, Retinal Dystrophies, Headache, Hypohidrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Affected | Patients with auto-inflammatory disorders | |
| Family Members | Family members of patients | |
| Healthy Volunteers | Healthy Volunteers |
What is being measured
The primary outcome is the main question the study is designed to answer.
Genetic linkage in autoinflammatory dise
discovery of genetic associations to autoinflammatory disorders
Measured: annually
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study start10 Mar 1994
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Familial Mediterranean Fever (FMF)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 5,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Human Genome Research Institute (NHGRI)
- Sponsor type
- US National Institutes of Health
- Collaborators
- University of Massachusetts, Worcester, Duke University, Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Benjamin D Solomon, M.D., Principal investigator, National Human Genome Research Institute (NHGRI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001373
- Sponsor's protocol ID
- 940105
- Other IDs
- 94-HG-0105
- Status last verified
- 4 Sep 2026
- First submitted
- 3 Nov 1999
- Last updated
- 13 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual genomic sequencing data and corresponding phenotype data will be deposited in dbGaP as part of the study's Genomic Data Sharing Plan. Non-genomic and/or phenotypic individual data will not be deposited in shared databases for broad research use.
Publications
Hashkes PJ, Spalding SJ, Giannini EH, Huang B, Johnson A, Park G, Barron KS, Weisman MH, Pashinian N, Reiff AO, Samuels J, Wright DA, Kastner DL, Lovell DJ. Rilonacept for colchicine-resistant or -intolerant familial Mediterranean fever: a randomized trial. Ann Intern Med. 2012 Oct 16;157(8):533-41. doi: 10.7326/0003-4819-157-8-201210160-00003.
PubMed 23070486Aksentijevich I, Kastner DL. Genetics of monogenic autoinflammatory diseases: past successes, future challenges. Nat Rev Rheumatol. 2011 Jul 5;7(8):469-78. doi: 10.1038/nrrheum.2011.94.
PubMed 21727933Bulua AC, Mogul DB, Aksentijevich I, Singh H, He DY, Muenz LR, Ward MM, Yarboro CH, Kastner DL, Siegel RM, Hull KM. Efficacy of etanercept in the tumor necrosis factor receptor-associated periodic syndrome: a prospective, open-label, dose-escalation study. Arthritis Rheum. 2012 Mar;64(3):908-13. doi: 10.1002/art.33416.
PubMed 22006113