Trial record 6 of 37 for:    FAMILIAL MEDITERRANEAN FEVER

Familial Mediterranean Fever and Related Disorders: Genetics and Disease Characteristics

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by National Institutes of Health Clinical Center (CC)
University of Massachusetts, Worcester
Duke University
Information provided by:
National Institutes of Health Clinical Center (CC) Identifier:
First received: November 3, 1999
Last updated: March 14, 2014
Last verified: December 2013

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:

  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.

Periodic Disease

Study Type: Observational
Official Title: Genetics and Pathophysiology of Familial Mediterranean Fever and Related Disorders

Resource links provided by NLM:

Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 99999999
Study Start Date: March 1994
Detailed Description:

The purpose of this protocol is to study the genetics and pathophysiology of familial Mediterranean fever (FMF) and other related diseases. FMF is a recessively inherited condition characterized by episodes of fever and serositis or synovitis; some patients also develop systemic amyloidosis. Our laboratory has identified the FMF gene and several disease-related mutations. The FMF gene encodes a protein called pyrin that is the prototype of a family of molecules involved in the regulation of apoptosis (cell-death) and inflammation. The precise biochemical mechanism by which these proteins function, and by which mutations cause disease, is still unknown.

There are a number of other conditions, sometimes referred to as autoinflammatory syndromes because of the lack of high-titer autoantibodies or antigen-specific T-cells that are also characterized by episodic inflammation. Seven are caused by mutations in five other genes: the TNF-receptor associated periodic syndrome (TRAPS) is caused by mutations in one of the receptors for tumor necrosis factor (TNF); the hyperimmunoglobulinemia D with periodic fever syndrome (HIDS) is caused by mutations in the gene encoding mevalonate kinase; Muckle-Wells syndrome (MWS), familial cold autoinflammatory syndrome (FCAS), and neonatal-onset multisystem inflammatory disease (NOMID) are caused by mutations in the gene encoding cryopyrin, a member of the aforementioned pyrin family of proteins; deficiency of the interleukin-1 receptor antagonist (DIRA) is caused by mutations in the gene that codes for the interleukin-1 receptor antagonist, a protein that helps to regulate levels of the inflammatory cytokine, interleukin-1; and the syndrome of pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) is caused by mutations in PSTPIP1, a protein that binds pyrin. In addition, there are patients with episodic fevers and/or inflammation who do not have identifiable mutations in any of these genes. Some of these latter cases appear to cluster in families, while others are sporadic.

The goals of this protocol are: 1) to gather and evaluate clinical data on selected patients with FMF and related conditions, so as to characterize more thoroughly the clinical features and natural history of patients with recognized disorders as well as those with as yet undefined autoinflammatory conditions; 2) to identify mutations, both in known autoinflammatory genes and in other genes, that lead to syndromes of periodic inflammation, and to study possible correlations between specific genetic mutations and disease manifestations; and 3) to undertake functional, biochemical, and molecular studies of leukocytes from patients with both known and as yet poorly defined autoinflammatory conditions.

Patients will undergo screening history, physical examination, and clinical laboratory evaluation, usually in the outpatient department. Imaging studies and skin or muscle biopsies may be performed when clinically indicated. Where appropriate, we will ask probands to obtain permission from family members to be contacted. We will collect blood samples from consenting affected individuals and, in some cases, unaffected family members, extract DNA, and perform molecular genetic analyses. For cellular and biochemical studies, we will obtain blood samples and possibly salivary samples from patients, selected unaffected family members, and unrelated controls. In some cases adult patients may be asked to interrupt treatment temporarily to obtain additional blood samples. We may also ask a small number of adult patients to undergo leukapheresis and/or bone marrow aspiration for research purposes.


Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes

    1. Individuals referred to the NIH with a possible diagnosis of FMF, TRAPS, HIDS, MWS, FCAS, NOMID, DIRA, PAPA, PFAPA, or other unexplained febrile or inflammatory illnesses. Individuals may be seen for initial evaluation, genetic studies, and research blood specimens, or may send blood or saliva samples for genetic testing only. However, we place the following age restrictions on other studies:

      1. Leukapheresis will only be performed on individuals over the age of 18 years;
      2. Brief interruption of ongoing therapy for research blood sampling will only be proposed to individuals over the age of 18 years;
      3. Research bone marrow aspirations and biopsies will only be performed on individuals over the age of 18 years.
    2. Family members of individuals included under item 1: may be seen for initial evaluations, genetic studies, or research blood specimens, or may send blood or buccal samples for genetic testing only. Unaffected family members will not be asked to undergo leukapheresis, interruption of ongoing therapy, or bone marrow aspirations and biopsies.
    3. Controls for cellular, molecular, biochemical assays and genetic studies: Individuals who undergo phlebotomy specifically to provide a random control specimen will be required to be over the age of 7 years and not pregnant. Individuals providing a control specimen who are already undergoing phlebotomy for other reasons must be greater than 1 year of age and not pregnant.


  1. In the case of adults, inability to provide informed consent and unavailability of a legally authorized representative (LAR) to provide surrogate consent.
  2. In the case of minors, unavailability of a parent or guardian.
  3. Presence of any medical condition that would, in the opinion of the investigators, confuse the interpretation of the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00001373

Contact: Daniel L Kastner, M.D. (301) 402-2023

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010   
Sponsors and Collaborators
University of Massachusetts, Worcester
Duke University
Principal Investigator: Daniel L Kastner, M.D. National Human Genome Research Institute (NHGRI)
  More Information

Additional Information:
Publications: Identifier: NCT00001373     History of Changes
Other Study ID Numbers: 940105, 94-HG-0105
Study First Received: November 3, 1999
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Familial Mediterranean Fever
Hyper IgD Sydrome (HIDS) / Mevalonate kinase deficiency
Tumor necrosis factor receptor-associated periodic syndrome (TRAPS)
Muckle-Wells syndrome
Familial cold autoinflammatory syndrome (FCAS)
Neonatal onset multisystem inflammatory disease (NOMID)

Additional relevant MeSH terms:
Familial Mediterranean Fever
Hereditary Autoinflammatory Diseases
Gram-Negative Bacterial Infections
Bacterial Infections
Genetic Diseases, Inborn
Skin Diseases, Genetic
Skin Diseases processed this record on October 19, 2014