Familial Mediterranean Fever and Related Disorders: Genetics and Disease Characteristics

NCT00001373 | Recruiting

• 2 other identifiers: 94010594-HG-0105
• Study Type: observational
• Target: 5,000
• Locations: 1 country
• Sites: 5

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. 1.X-rays
2. 2.Consultations with specialists
3. 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. 4.Additional blood samples a maximum of 1 pint (450 ml) during a 6-week period for studies of white cell adhesion (stickiness)
5. 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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Genetic linkage in autoinflammatory dise

  discovery of genetic associations to autoinflammatory disorders

  annually

Study Arms (3)

Affected

Patients with auto-inflammatory disorders

Family Members

Family members of patients

Healthy Volunteers

Healthy Volunteers

Eligibility Criteria

• Age: 2 Months - 115 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• 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.
• 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);

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Human Genome Research Institute (NHGRI): lead
• University of Massachusetts, Worcester: collaborator
• Duke University: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (5)

Childrens National Medical Center

Washington D.C., District of Columbia, 20010, United States

COMPLETED

Johns Hopkins University

Baltimore, Maryland, 21205, United States

COMPLETED

Walter Reed National Medical Center

Bethesda, Maryland, 20301, United States

COMPLETED

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

University of Pittsburgh

Pittsburgh, Pennsylvania, 15261, United States

NOT YET RECRUITING

Related Publications (3)

• 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.

  PMID: 23070486 BACKGROUND

• 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.

  PMID: 21727933 BACKGROUND

• 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.

  PMID: 22006113 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Familial Mediterranean Fever; Hereditary Autoinflammatory Diseases; Fever; Genetic Diseases, Inborn; Splenomegaly; Retinal Dystrophies; Headache; Hypohidrosis

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Skin Diseases; Skin and Connective Tissue Diseases; Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hypertrophy; Pathological Conditions, Anatomical; Retinal Degeneration; Retinal Diseases; Eye Diseases; Pain; Neurologic Manifestations; Sweat Gland Diseases

Study Officials

• Benjamin D Solomon, M.D.

  National Human Genome Research Institute (NHGRI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amanda K Ombrello, M.D.

CONTACT

(301) 827-4258; ombrelloak@mail.nih.gov

Benjamin D Solomon, M.D.

CONTACT

(301) 402-8824; solomonb@mail.nih.gov

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: March 10, 1994
• Last Updated: April 16, 2026

Record last verified: 2026-04-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: 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.

Locations

US (5)