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Trial record 2 of 18 for:    NOMID

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 : November 26, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Tracking Information
First Submitted Date November 23, 2016
First Posted Date November 28, 2016
Last Update Posted Date November 26, 2019
Actual Study Start Date December 9, 2016
Estimated Primary Completion Date August 31, 2031   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: November 23, 2016)
To study the pathogenesis of patients affected with autoinflammatory diseases, including their clinical, immunological, genetic and metabolic-endrocrinological characteristics. [ Time Frame: Baseline, 1-2 years, 3-5 years, 10 years ]
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: November 23, 2016)
  • 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. [ 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 [ Time Frame: 1-2 years, 3-5 years, 10 years ]
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Natural History, Pathogenesis, and Outcome of Autoinflammatory Diseases (NOMID/CAPS, DIRA, CANDLE, SAVI, NLRC4-MAS, Still'S-like Diseases, and Other Undifferentiated Autoinflammatory Diseases)
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)
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 inflammation 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/CIAS1. Since then, we have identified additional mutations that cause autoinflammatory diseases, including mutations in proteasome components and in TMEM173/STING that suggest a role of increased type I IFN signaling as a contributor to the disease pathogenesis of autoinflammatory diseases. In this natural history study, we seek to comprehensively evaluate people with autoinflammatory diseases from clinical, genetic, immunologic, and endocrinologic perspectives. Other rare diseases not mediated by IL-1 or type I IFN and presumed to be autoinflammatory diseases with unknown genetic causes are also eligible under this protocol. In addition, we intend to evaluate long-term outcomes and biomarkers over time. We plan to follow most participants for the duration of this study (15 years). Relatives who do not have autoinflammatory disease as well as healthy volunteers will also be recruited to serve as controls for biomarker, genetic, and other molecular analyses.
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Study population is quite diverse as affected participants are from all over the world.
Condition
  • NOMID
  • DIRA
  • NLRC4-MAS
  • SAVI
  • CANDLE
Intervention Not Provided
Study Groups/Cohorts
  • 1
    Participants age 0-99 will have a known autoinflammatory disease
  • 2
    Unaffected relatives age 3-99 years
  • 3
    Healthy Volunteers age 18-99 years
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: November 23, 2016)
2200
Original Estimated Enrollment Same as current
Estimated Study Completion Date September 30, 2032
Estimated Primary Completion Date August 31, 2031   (Final data collection date for primary outcome measure)
Eligibility Criteria
  • INCLUSION CRITERIA - AFFECTED PARTICIPANTS:

    1. 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 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.

    2. Is willing to allow storage of biological specimens for future use in medical research.
    3. Is willing to allow genetic testing on collected biological samples.
    4. Has a primary care or other physician who will manage all health conditions related or unrelated to the study objectives.
    5. Fulfills one of the following criteria:

      • Has a known disease-causing genetic mutation associated with NOMID/CAPS, DIRA, CANDLE, SAVI, or NLRC4-MAS.
      • 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:

        • 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).
      • 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:

        • 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
      • 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.
    6. Alternatively to #5, be currently enrolled as an affected participant on NIAMS study 03-AR-0173.

INCLUSION CRITERIA - UNAFFECTED RELATIVES OF AFFECTED PARTICIPANTS:

  1. 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 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.)
  2. Be related by blood to an affected participant.
  3. Is willing to allow storage of biological samples for future use in medical research.
  4. Is willing to allow genetic testing on collected biological samples.
  5. Does not fulfill any of inclusion criterion #5 for affected participants.

INCLUSION CRITERIA - HEALTHY VOLUNTEERS:

  1. Be at least 18 years old.
  2. Not be related to an affected participant.
  3. s willing to allow storage of biological samples for future use in medical research.
  4. Is willing to allow genetic testing on collected biological samples.
  5. Does not fulfill any of inclusion criterion #5 for affected participants.

PARTICIPANT EXCLUSION CRITERIA:

  1. 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.
  2. 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.
Sex/Gender
Sexes Eligible for Study: All
Ages 2 Years to 99 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts
Contact: Raphaela T Goldbach-Mansky, M.D. (301) 761-7553 goldbacr@mail.nih.gov
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT02974595
Other Study ID Numbers 170016
17-I-0016
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
Study Sponsor National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators Not Provided
Investigators
Principal Investigator: Raphaela T Goldbach-Mansky, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date November 22, 2019