ClinicalTrials.gov record NCT00001373
Familial Mediterranean Fever and Related Disorders: Genetics and Disease Characteristics
An Exploratory Study of the Genetics, Pathophysiology, and Natural History of Autoinflammatory Diseases
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
A prospective natural-history (observational) study of people with known or suspected autoinflammatory diseases, their relatives, and healthy volunteers. Participants give medical history, undergo exams, and provide blood, urine, saliva or DNA samples; some may have X-rays, skin biopsy, leukapheresis, or bone marrow procedures. Participants may be followed about every six months and offered genetic counseling by the study team.
What it is studying. The study seeks to discover genetic variants (inherited and somatic) linked to autoinflammatory diseases, to describe immune-cell and molecular features, and to define clinical patterns and genotype–phenotype relationships.
What the researchers hope to learn. Primary goal: discover rare and common genetic variants, structural genomic changes, and somatic mutations that cause or raise risk for inflammatory disease. Secondary goals: describe immune cell populations, inflammatory mediators, gene expression and epigenetic features, and perform functional assays on leukocytes. Tertiary goals: characterize clinical features of poorly described or newly defined inflammatory disorders and develop condition-specific endpoints.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
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:
- X-rays
- Consultations with specialists
- DNA sample collection (blood or saliva sample) for genetic studies. These might include studies of specific genes, or more complete sequencing of the genome.
- Additional blood samples a maximum of 1 pint (450 ml) during a 6-week period for studies of white cell adhesion (stickiness)
- 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....
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
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:
- 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);
- 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
- 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
- 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.
Study description and what participation involves
The study's detailed description, as published on ClinicalTrials.gov.
Show the detailed description from the registry
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.
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
Participation typically involves a medical and family history, a physical exam, routine blood and urine tests, and possible follow-up visits about every six months; the study may also review your medical records. Participants will provide DNA samples (blood or saliva) for genetic studies and will be offered genetic counseling about risks and treatment options. Some participants may be asked for extra blood for research: patients up to 1 pint (450 mL) within a 6-week period; relatives up to 550 mL within an 8-week period; healthy volunteers typically up to 90 mL (with up to 1 pint over 6 weeks possible in the future). A small number of subjects may undergo more invasive procedures such as leukapheresis, skin biopsy, or bone marrow aspiration and biopsy; the study may also include X-rays, specialist consultations, or a 24-hour urine collection for some participants.
How the study is structured. This is a prospective observational cohort study with three groups: affected patients, family members, and healthy volunteers. No treatments are assigned. Participants provide medical and family history, undergo physical exams, and give samples (blood, urine, saliva/DNA); a subset may undergo more involved procedures named in the record (for example, leukapheresis, skin biopsy, or bone marrow aspiration/biopsy). Clinical data and samples may be collected over time (about every six months) for genetic and immunologic analyses.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- This is an observational study, so the study itself gives no treatment. What would taking part involve for me, and would it change my usual care?
- The listed sites are in United States. Is any of them reachable for me, and does the study help with travel?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on familial Mediterranean fever
Important dates
- Study start
- Mar 10, 1994
- Target enrollment
- 5000 participants (estimated)
- Last updated on registry
- Oct 8, 2026
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- National Human Genome Research Institute (NHGRI)
- Collaborators
- University of Massachusetts, Worcester
- Duke University
- Merck Sharp & Dohme LLC
Central study contact
If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.
- Amanda K Ombrello, M.D. 📞 (301) 827-4258 ✉ ombrelloak@mail.nih.gov
- Benjamin D Solomon, M.D. 📞 (301) 402-8824 ✉ solomonb@mail.nih.gov
Participating sites (5)
- Childrens National Medical CenterCompleted
Washington D.C., District of Columbia, 20010 · United States
- Johns Hopkins UniversityCompleted
Baltimore, Maryland, 21205 · United States
- Walter Reed National Medical CenterCompleted
Bethesda, Maryland, 20301 · United States
- National Institutes of Health Clinical CenterRecruiting
Bethesda, Maryland, 20892 · United States
- NIH Clinical Center Office of Patient Recruitment (OPR) · 800-411-1222 ext. TTY dial 711 · ccopr@nih.gov
- University of PittsburghNot Yet Recruiting
Pittsburgh, Pennsylvania, 15261 · United States
- Daniella Schwartz · 412-648-1587 · Daniella.Schwartz@pitt.edu
Terms used on this page · explanations by MedicalUpdates.ai
- natural history study
- A study that follows how a condition changes over time without assigning an experimental treatment. It may involve study visits and tests, and is often used to plan future trials.
- follow-up
- The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes.
- Legally Authorized Representative
- A person who is legally allowed to make decisions, including consent to research, on behalf of someone who cannot consent for themselves.
- written informed consent
- The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
- INCLUSION CRITERIA
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- EXCLUSION CRITERIA
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
- biopsy
- Removal of a small piece of tissue so it can be examined under a microscope. 'Biopsy-proven' or 'histologically confirmed' means the diagnosis was confirmed by examining tissue under a microscope.
- Primary Objective
- The main result the study is designed to measure and report on. Other results, called secondary outcomes, are also collected.
- Secondary Objective
- An additional result the study measures alongside the primary outcome, for example quality of life or a laboratory value.
- enrollment
- The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
- Endpoints
- Something the study measures to judge its results, such as a symptom score, a blood test or survival. Outcomes are grouped as primary, secondary and sometimes exploratory.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
← Back to clinical trials