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RecruitingNCT00001373Updated Nov 9, 2026

Familial Mediterranean Fever and Related Disorders: Genetics and Disease Characteristics

An observational study in Familial Mediterranean Fever (FMF), Autoinflammation and Periodic Fever, sponsored by National Human Genome Research Institute (NHGRI). Recruiting at 5 sites in United States. Open to participants aged 2 Months to 115 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-11-09.

Sponsored by National Human Genome Research Institute (NHGRI) · Observational

From the registry’s dates

  • Started Mar 1994; still recruiting 32 years 8 months later.
Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
5,000
Ages
2 Months to 115 Years
Sex
All
01

Study 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.

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.

02

Conditions studied

  • Familial Mediterranean Fever (FMF)
  • Autoinflammation
  • Periodic Fever
  • Fever
  • Genetic Diseases
  • ROSAH
  • ALPK1

Keywords

  • Splenomegaly
  • Retinal Dystrophy
  • Periodic Fever
  • Optic Nerve Edema
  • HEADACHE
  • Genetics
  • Familial Mediterranean
  • Autoinflammation
  • Anhidrosis
  • Alpha-Kinase 1
03

In context

Familial Mediterranean Fever

61 studies on the registry are indexed under Familial Mediterranean Fever; 27 are open to participants now.

This study's planned enrollment of 5,000 is above the median of 89 across 30 observational studies indexed under Familial Mediterranean Fever.

Browse Familial Mediterranean Fever studies →

Lead sponsor

National Human Genome Research Institute (NHGRI) is the lead sponsor of 203 studies on the registry; 33 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
2 Months to 115 Years
Sexes eligible
All
Accepts healthy volunteers
Yes
Sampling method
Non-probability sample

Study population

Patients with autoinflammatory disorders and unaffected family members, and healthy volunteers.

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

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:

  1. Stated willingness to participate in study procedures (which at the very least includes providing a mail-in sample for genetic analysis);
  2. Regardless of gender, at least one month of age;
  3. A medical history that, in the expert opinion of the study team, is consistent with the possibility of autoinflammatory disease; and
  4. Ability of the subject, parents (in the case of children), or Legally Authorized Representative to understand and the willingness to sign a written document.

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:

  1. Stated willingness to participate in study procedures (which at the very least includes providing a mail-in sample for genetic analysis);
  2. Regardless of gender, at least one month of age;
  3. Relationship, either by blood or marriage, to an individual enrolled or about to be enrolled in the study with known or suspected autoinflammatory disease;
  4. 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
  5. 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:

  1. Stated willingness to participate in study procedures for healthy volunteers;
  2. Regardless of gender, at least one year old, and not pregnant (by history of a missed menstrual period);
  3. 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
  4. Ability of the subject or parents (in the case of children) to understand and the willingness to sign a written informed consent document.

Exclusion criteria

EXCLUSION 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.

Terms in these criteria, in plain language(1)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

05

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
5,000 participants (estimated)

Groups and cohorts

  • Affected

    Patients with auto-inflammatory disorders

  • Family Members

    Family members of patients

  • Healthy Volunteers

    Healthy Volunteers

06

What researchers measure

Primary outcomes

  1. Genetic linkage in autoinflammatory dise

    discovery of genetic associations to autoinflammatory disorders

    Time frame: annually

07

Study locations

1 of 5 sites recruiting
  • Childrens National Medical Center
    Washington D.C., District of Columbia 20010, United States
    Completed

    Not enrolling at this site.

  • Johns Hopkins University
    Baltimore, Maryland 21205, United States
    Completed

    Not enrolling at this site.

  • Walter Reed National Medical Center
    Bethesda, Maryland 20301, United States
    Completed

    Not enrolling at this site.

  • National Institutes of Health Clinical Center
    Bethesda, Maryland 20892, United States
    Recruiting
    • NIH Clinical Center Office of Patient Recruitment (OPR) · Contactccopr@nih.gov · 800-411-1222
  • University of Pittsburgh
    Pittsburgh, Pennsylvania 15261, United States
    Not yet recruiting
08

References and documents

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 23070486 ↗
  • Aksentijevich 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 21727933 ↗
  • Bulua 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 ↗

Individual participant data

Plan to share: 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.

Supporting information: Study protocol, Analytic code

Time frame: Genomic Sharing Plan in effect since 2018 with genomic data deposited to dbGaP for broad availability within six months of final data analysis of each genomic sequence. No end date of data availability through dbGaP.

Access criteria: Genomic sequences will be deposited to dbGaP following final sequence analysis and available for broad use, as determined by dbGaP usage committee.

09

Timeline

4 registry updates since Sep 25, 2026

Started Mar 1994 (actual).

How these figures are worked out, and which studies are left out of them.

Registered
Nov 3, 1999
First posted
Nov 4, 1999
StartActual
Mar 10, 1994
Last update
Nov 9, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
Minor edits
Nothing that changes what the study is or who can join. Edited: description
4 updates, last Nov 9, 2026
Show all 4 updates
  1. Nov 9, 2026
    Minor edits only
    + 1 other change: description
  2. Nov 5, 2026
    Minor edits only
    + 1 other change: description
  3. Oct 13, 2026
    Minor edits only
    + 1 other change: description
  4. Oct 8, 2026
    Minor edits only
    + 1 other change: description

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT00001373
Responsible party
Sponsor
First posted
Nov 4, 1999
Start date
Mar 10, 1994
Last update
Nov 9, 2026

Study contacts

Amanda K Ombrello, M.D.
Contact
ombrelloak@mail.nih.gov
(301) 827-4258
Benjamin D Solomon, M.D.
Contact
solomonb@mail.nih.gov
(301) 402-8824
Benjamin D Solomon, M.D.
principal investigator · National Human Genome Research Institute (NHGRI)

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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