Natural History, Pathogenesis, and Outcome of Autoinflammatory Diseases (NOMID/CAPS, DIRA, CANDLE, SAVI, NLRC4-MAS, Still'S-like Diseases, and Other Undifferentiated Autoinflammatory Diseases)
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ClinicalTrials.gov Identifier: NCT02974595 |
Recruitment Status :
Recruiting
First Posted : November 28, 2016
Last Update Posted : January 16, 2024
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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:
- Clinical tests that help assess organ damage and function such as hearing, vision, memory, and learning tests.
- Imaging studies to characterize organ involvement of the inflammatory disease including: X-rays, CT scans, special MRIs, and bone scans.
- Laboratory evaluations including clinical markers of disease activity, research samples for genetic studies, blood samples for cytokine/biomarker assessment, and gene expression profiling.
- Questionnaires to assess disease activity and quality of life.
- 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.
Condition or disease |
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NOMID DIRA NLRC4-MAS SAVI CANDLE |
Study Type : | Observational |
Estimated Enrollment : | 3200 participants |
Observational Model: | Cohort |
Time Perspective: | Prospective |
Official Title: | Studies of the Natural History, Pathogenesis, and Outcome of Autoinflammatory Diseases (NOMID/CAPS, DIRA, CANDLE, SAVI, NLRC4-MAS, Still'S-like Diseases, and Other Undifferentiated Autoinflammatory Diseases) |
Actual Study Start Date : | December 9, 2016 |
Estimated Primary Completion Date : | August 31, 2031 |
Estimated Study Completion Date : | September 30, 2032 |
Group/Cohort |
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Affected Participants
Individuals with undifferentiated autoinflammatory diseases or genetically defined conditions, such as NOMID/CAPS, DIRA, CANDLE, SAVI, and NLRC4 MAS.
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Healthy Volunteer
Volunteers without known autoinflammatory disease who consent to providing blood specimen for genetic testing.
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Unaffected Relatives
Blood relatives of the affected patients without known autoinflammatory disease who consent to providing specimen for genetic testing.
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- To study the pathogenesis of patients affected with auto-inflammatory diseases, including their clinical, immunological, genetic and metabolic/endocrinological characteristics. [ Time Frame: 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.
- Longitudinal fluctuations in clinical and biomarker characteristics of autoinflammatory diseases [ Time Frame: 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) [ Time Frame: 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.
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Ages Eligible for Study: | up to 99 Years (Child, Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
Sampling Method: | Non-Probability Sample |
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INCLUSION CRITERIA - AFFECTED PARTICIPANTS:
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Be 2 to 99 years old for participants who will be seen at the NIH CC; be 0 (newborn) to 99 years old for participants who participate remotely via a virtual protocol visit and will submit mail-in samples. Participants younger than 3 years will be seen in the outpatient clinic at the NIH CC if approved by the Pediatric
Consult Service as per NIH CC policy and guidelines.
- Is willing to allow storage of biological specimens for future use in medical research.
- Is willing to allow genetic testing on collected biological samples.
- Has a primary care or other physician who will manage all health conditions related or unrelated to the study objectives.
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Fulfills one of the following criteria:
- Has a known disease-causing genetic mutation associated with NOMID/CAPS, DIRA, CANDLE, SAVI, or NLRC4-MAS.
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Has clinical signs or symptoms not explained by any other disorder (eg, infections, malignancies) and are consistent with a possible IL-1 mediated autoinflammatory disease. Participants must meet both of the following criteria:
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Clinical characteristics strongly consistent with an IL-1 mediated autoinflammatory disease per the following criteria and at the discretion of the principal investigator (PI). Individuals must have a past or present history of one of the following to be considered for study enrollment:
- Recurrent fever that has gone undiagnosed after reasonable attempts, and that is consistent with the conditions under study in this protocol
- Neutrophilic urticaria, pustular dermatitis, erysipelas-like erythema, or urticarial rash
- Epiphyseal and/or patella enlargement, periostitis, myalgias, arthralgias, arthritis, or recurrent multifocal aseptic osteomyelitis
- Sensorineural hearing loss
- Chronic aseptic meningitis or CNS vasculitis
- Conjunctivitis, episcleritis, uveitis, papilledema, pleuritis, pericarditis, aseptic peritonitis, early onset enterocolitis, hepatosplenomegaly, or lymphadenopathies
- Laboratory characteristics strongly consistent with an IL-1mediated autoinflammatory disease per the following criteria. Individuals must havepast or present history of evidence of systemic inflammation (eg, elevation of C-reactive protein [CRP] and/or erythrocyte sedimentation rate [ESR], anemia, thrombocytosis).
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Has clinical signs or symptoms not explained by any other disorder (eg, infections, malignancies) and are consistent with a possible IFN-mediated, autoinflammatory disease.1,36 Participants must meet both of the following criteria:
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Clinical characteristics strongly consistent with an IFN-mediated autoinflammatory disease per the following criteria and at the discretion of the PI. Individuals must have a past or present history of one of the following to be considered for study enrollment:
- Recurrent fevers that has gone undiagnosed after reasonable attempts, and that is consistent with the conditions under study in this protocol
- Panniculitis, ischemic ulcerative skin lesions, chilblain lesions, or livedo reticularis
- Lipodystrophy
- Myositis, arthralgias, arthritis, or joint contractures
- Basal ganglia calcifications or white matter CNS disease
- Interstitial lung disease, lung fibrosis, or pulmonary hypertension
- Conjunctivitis, episcleritis, cortical blindness, glaucoma, papilledema, or hepatosplenomegaly
- Laboratory characteristics strongly consistent with an IFN-mediated autoinflammatory disease per the following criteria. Individuals must have past or present history one or more of the following to be considered for study enrollment:
- Evidence of systemic inflammation (eg, ESR or CRP)
- Cytopenias (eg. leukopenia, anemia, or thrombocytopenia)
- Dyslipidemia or insulin resistance
- Abnormal liver function test, creatinine kinase (CK), or LDH
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Has clinical signs or symptoms consistent with an undifferentiated autoinflammatory disease (including but not limited to dysregulation in other proinflammatory cytokines such as IL-17, TNF, IL-18, and others). Participants must meet one of the following criteria:
- Clinical characteristics strongly consistent with an undifferentiated autoinflammatory disease. Individuals must have a past or present history of one of the clinical and one of the laboratory characteristics mentioned above to be considered for study enrollment.
- Individuals with defined organ inflammation associated with past or current evidence of systemic inflammation.
- Alternatively to #5, had been enrolled in the past as an affected participant on NIAMS study 03-AR-0173 and or had samples collected on 03-AR-0173.
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INCLUSION CRITERIA - UNAFFECTED RELATIVES OF AFFECTED PARTICIPANTS:
- Be 2 to 99 years old for participants who will be seen at the NIH CC; be 0 (newborn) to 99 years old for participants who participate remotely via a virtual protocol visit and will submit mail-in samples. Participants younger than 3 years will be seen in the outpatient clinic at the NIH CC if approved by the Pediatric Consult Service as per NIH CC policy and guidelines.)
- Be related by blood to an affected participant.
- Is willing to allow storage of biological samples for future use in medical research.
- Is willing to allow genetic testing on collected biological samples.
- Does not fulfill any of inclusion criterion #5 for affected participants.
- Is able to provide informed consent.
INCLUSION CRITERIA - HEALTHY VOLUNTEERS:
- Be at least 18 years old.
- Not be related to an affected participant.
- s willing to allow storage of biological samples for future use in medical research.
- Is willing to allow genetic testing on collected biological samples.
- Does not fulfill any of inclusion criterion #5 for affected participants.
- Is able to provide informed consent.
PARTICIPANT EXCLUSION CRITERIA:
- Presence of conditions that, in the judgment of the investigator, may put the participant at undue risk or make them unsuitable for participation in the study.
- Oncological evaluation suggestive of lymphoma, leukemia or multiple myeloma, except for participants with a known primary diagnosis of an autoinflammatory disease who subsequently developed a malignancy. These patients will not be excluded from the study.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02974595
Contact: Katsiaryna Uss | (240) 292-4709 | kat.uss@nih.gov | |
Contact: Raphaela T Goldbach-Mansky, M.D. | (301) 761-7553 | goldbacr@mail.nih.gov |
United States, Maryland | |
National Institutes of Health Clinical Center | Recruiting |
Bethesda, Maryland, United States, 20892 | |
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 prpl@cc.nih.gov |
Principal Investigator: | Raphaela T Goldbach-Mansky, M.D. | National Institute of Allergy and Infectious Diseases (NIAID) |
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | National Institute of Allergy and Infectious Diseases (NIAID) |
ClinicalTrials.gov Identifier: | NCT02974595 |
Other Study ID Numbers: |
170016 17-I-0016 |
First Posted: | November 28, 2016 Key Record Dates |
Last Update Posted: | January 16, 2024 |
Last Verified: | January 11, 2024 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | .As outlined in our approved GDS Plan (dated 09/27/2019): Whole exome and whole genome sequencing data |
Supporting Materials: |
Study Protocol |
Time Frame: | As outlined in our approved GDS Plan (dated 09/27/2019) and protocol: Following genetic testing, the data will be shared in a controlled-access public database for other investigators to benefit from it (eg, dbGaP, the Database of Genotypes and Phenotypes). |
Access Criteria: | Other NIH and non-NIH investigators may use these data/specimens for research purposes. @@@IRB review and approval will be obtained for all research involving identifiable data/specimen, including any coded and linked samples or data that can be linked back to the respective subjects.@@@@@@We will share human data generated in this study for future research through:@@@Our NIH-funded and approved public repository for genetic and RNA sequence data: De-identified data will be shared per our approved Genetic Data Sharing Plan. @@@BTRIS (Biomedical Translational Research Information System) sharing activities in the NIH Clinical Center (CC): includes Identifiable data generated in CC. @@@Appropriate individual regulatory approvals will govern sharing of data/specimens with outside collaborators.@@@Data will be shared with medical professionals involved in clinical care of each patient to assist with medical care of the patient. @@@Publication and/or public presentations. @@@ |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
Study of pathogenesis of patients affected with autoinflammatory diseases This Includes the Clinical, Immunological , Genetic, and Metabolic Characteristi Collection of Clinical and Laboratory Outcome Data Evaluation of Characteristics/Disease Manifestations Natural History |
Hereditary Autoinflammatory Diseases Cryopyrin-Associated Periodic Syndromes Genetic Diseases, Inborn Skin Diseases, Genetic Skin Diseases Chronic Inducible Urticaria Chronic Urticaria Urticaria |
Skin Diseases, Vascular Cold Urticaria Hypersensitivity, Immediate Hypersensitivity Immune System Diseases Chronic Disease Disease Attributes Pathologic Processes |