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Protocol Details

Genetics and Pathophysiology of Autoinflammatory Disorders.

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Human Genome Research Institute (NHGRI)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: N/A
Max Age: N/A

Referral Letter Required


Population Exclusion(s)


Special Instructions

Currently Not Provided


familial mediterranean fever;
Periodic fever

Recruitment Keyword(s)



familial mediterranean fever (FMF)

Investigational Drug(s)


Investigational Device(s)




Supporting Site

National Human Genome Research InstituteUniversity of MassachusettsDuke University Medical CenterMerck

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.

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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:

a) Leukapheresis will only be performed on individuals over the age of 18 years;

b) Brief interruption of ongoing therapy for research blood sampling will only be proposed to 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 or, interruption of ongoing therapy.

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.

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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.

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.

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.

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Principal Investigator

Referral Contact

For more information:

Daniel L. Kastner, M.D.
National Human Genome Research Institute (NHGRI)
BG 50 RM 5222
(301) 402-2023

Amanda K. Ombrello, M.D.
National Human Genome Research Institute (NHGRI)
BG 10 RM 4N208
(301) 827-4258

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Clinical Trials Number:


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