NCT00001373

Familial Mediterranean Fever and Related Disorders: Genetics and Disease Characteristics

Recruiting now Last updated 16 April 2026

What this trial tests

trial in Familial Mediterranean Fever (FMF) in 5,000 participants. Currently enrolling.

Timeline

10 March 1994

Quick facts

Lead sponsor	National Human Genome Research Institute (NHGRI)
Status	Recruiting now
Study type	OBSERVATIONAL
Enrollment	5,000
Start date	10 March 1994
Sites	5 locations across United States

Conditions studied

• Familial Mediterranean Fever (FMF) — all drugs for Familial Mediterranean Fever (FMF) →
• Autoinflammation — all drugs for Autoinflammation →
• Periodic Fever — all drugs for Periodic Fever →
• Fever — all drugs for Fever →

Sponsor

National Human Genome Research Institute (NHGRI)

Who can join

Adults 2 Months to 115, any sex, with Familial Mediterranean Fever (FMF) or Autoinflammation. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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....

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Benign and malignant hematologic manifestations in patients with VEXAS syndrome due to somatic mutations in UBA1.
   Obiorah IE, Obiorah IE, Patel BA, Groarke EM, et al · · 2021 · cited 177× · PMID 34427584 · DOI 10.1182/bloodadvances.2021004976
2. Efficacy of etanercept in the tumor necrosis factor receptor-associated periodic syndrome: a prospective, open-label, dose-escalation study.
   Bulua AC, Mogul DB, Aksentijevich I, Singh H, et al · · 2012 · cited 88× · PMID 22006113 · DOI 10.1002/art.33416
3. Early activation of inflammatory pathways in UBA1-mutated hematopoietic stem and progenitor cells in VEXAS.
   Wu Z, Gao S, Gao Q, Patel BA, et al · · 2023 · cited 49× · PMID 37586319 · DOI 10.1016/j.xcrm.2023.101160
4. A unified metric of human immune health.
   Sparks R, Rachmaninoff N, Lau WW, Hirsch DC, et al · · 2024 · cited 37× · PMID 38961223 · DOI 10.1038/s41591-024-03092-6
5. Venous and arterial thrombosis in patients with VEXAS syndrome.
   Kusne Y, Ghorbanzadeh A, Dulau-Florea A, Shalhoub R, et al · · 2024 · cited 33× · PMID 38306657 · DOI 10.1182/blood.2023022329
6. Biallelic human SHARPIN loss of function induces autoinflammation and immunodeficiency.
   Oda H, Manthiram K, Chavan PP, Rieser E, et al · · 2024 · cited 24× · PMID 38609546 · DOI 10.1038/s41590-024-01817-w
7. Ophthalmic Manifestations of ROSAH (Retinal Dystrophy, Optic Nerve Edema, Splenomegaly, Anhidrosis, and Headache) Syndrome, an Inherited NF κB-Mediated Autoinflammatory Disease with Retinal Dystrophy.
   Huryn LA, Kozycki CT, Serpen JY, Zein WM, et al · · 2023 · cited 24× · PMID 36332842 · DOI 10.1016/j.ophtha.2022.10.026
8. A clinical, histopathological, and molecular study of two cases of VEXAS syndrome without a definitive myeloid neoplasm.
   Li P, Venkatachalam S, Ospina Cordona D, Wilson L, et al · · 2022 · cited 11× · PMID 34649277 · DOI 10.1182/bloodadvances.2021005243