Natural History, Pathogenesis, and Outcome of Autoinflammatory Diseases (NOMID/CAPS, DIRA, CANDLE, SAVI, NLRC4-MAS, Still'S-like Diseases, and Other Undifferentiated Autoinflammatory Diseases)
- Conditions
- SAVICANDLEDIRANLRC4-MASNOMID
- Registration Number
- NCT02974595
- Brief Summary
Background:
Some diseases cause chronic inflammation with intermittent flares in the body. These are called autoinflammatory diseases. They can cause fevers, rashes, ulcers, and other problems. Researchers want to learn more about the causes and effects of these diseases. They hope this will improve how the disease is managed in the future.
Objectives:
To understand the underlying immune dysregulation
To identify the genetic cause
To translate our findings into novel treatments that improve patients disease outcomes
Eligibility:
Patients with known NOMID/CAPS, DIRA, CANDLE, SAVI, NLRC4-MAS, Still's Disease, and with other yet undifferentiated autoinflammatory diseases.
Unaffected relatives of participants with a known or undifferentiated autoinflammatory disease
Healthy adult volunteers at least 18 years of age
Design:
Participants will be screened with blood sample and medical history. They may provide copies of their medical records.
Enrolled participants will be evaluated at the NIH for 2-5 days. All participants will have a detailed medical history, physical exam, blood tests, and other evaluations depending on the extent of their autoinflammatory disease.
Participants may also expect the following assessments:
1. Clinical tests that help assess organ damage and function such as hearing, vision, memory, and learning tests.
2. Imaging studies to characterize organ involvement of the inflammatory disease including: X-rays, CT scans, special MRIs, and bone scans.
3. Laboratory evaluations including clinical markers of disease activity, research samples for genetic studies, blood samples for cytokine/biomarker assessment, and gene expression profiling.
4. Questionnaires to assess disease activity and quality of life.
5. If indicated, other procedures may be administered that include: a lumbar puncture if CNS inflammation is suspected, a skin biopsy if skin inflammation is present, and/or gastrointestinal and pulmonary procedures if they are clinically indicated.
Participants may return for a single follow-up visit or for long-term follow-up visits depending on their disease and willingness to return. Long-term follow-up may occur for up to 15 years on this protocol.
- Detailed Description
Autoinflammatory diseases are a group of immune dysregulatory diseases that are characterized by recurrent episodes of systemic as well as organ-specific inflammation that can involve the skin, eyes, joints, bones, muscles, lungs, serosal surfaces, inner ear, brain, and other organs. The prominent role of IL-1 in the pathogenesis of these disorders first became evident through the discovery of mutations in the gene NLRP3 and IL1RN. Since then, we have identified additional mutations that cause autoinflammatory diseases, including mutations in proteasome components and STING1 that suggest a role of increased type I IFN signaling as a contributor to the disease pathogenesis of autoinflammatory diseases and in NLRC4 and CDC42 that suggest a role of IL-18 in some autoinflammatory diseases. In this natural history study, we seek to comprehensively evaluate people with autoinflammatory diseases that include clinical, genetic, immunologic, andendocrinologic characterizations. Other rare diseases not mediated by IL-1, IL-18 or type I IFN and presumed to be autoinflammatory diseases with unknown genetic causes may also be eligible under this protocol. In addition, we intend to evaluate long-term outcomes and biomarkers over time in selected diseases. We plan to follow most participants for the duration of this study (15 years). Relatives who do not have autoinflammatory diseases as well as healthy volunteers will also be recruited to serve as controls for biomarker, genetic, and other molecular analyses.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 3200
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To study the pathogenesis of patients affected with auto-inflammatory diseases, including their clinical, immunological, genetic and metabolic/endocrinological characteristics. 1-2 years, 3-5 years, 10 years To study the pathogenesis of patients affected with autoinflammatory diseases, including their clinical, immunological, genetic and metabolic/endocrinological characteristics.
- Secondary Outcome Measures
Name Time Method Longitudinal fluctuations in clinical and biomarker characteristics of autoinflammatory diseases 1-2 years, 3-5 years, 10 years To evaluate clinical characteristics/disease manifestations and blood, body fluids, and tissue biomarkers during disease flares and quiescence.
Long term Organ specific outcome (clinical and biomarker evidence of both inflammation and damage accrual) 1-2 years, 3-5 years, 10 years To collect long-term clinical and laboratory outcome parameters of the multiorgan inflammatory involvement and/or organ damage in patients with genetically defined or undifferentiated autoinflammatory (immune-dysregulatory) diseases.
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States