Natural History, Pathogenesis, and Outcome of Autoinflammatory Diseases (NOMID/CAPS, DIRA, CANDLE, SAVI, NLRC4-MAS, Still'S-like Diseases, and Other Undifferentiated Autoinflammatory Diseases)

  • STATUS
    Recruiting
  • End date
    Sep 30, 2032
  • participants needed
    3200
  • sponsor
    National Institute of Allergy and Infectious Diseases (NIAID)
Updated on 19 June 2022
Accepts healthy volunteers

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.

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.

Details
Condition NOMID, DIRA, NLRC4-MAS, SAVI, CANDLE
Clinical Study IdentifierNCT02974595
SponsorNational Institute of Allergy and Infectious Diseases (NIAID)
Last Modified on19 June 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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
Has a primary care or other physician who will manage all health conditions related or unrelated to the study objectives
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
Laboratory characteristics strongly consistent with an IL-1mediated
Chronic aseptic meningitis or CNS vasculitis
autoinflammatory disease per the following criteria. Individuals must havepast
Conjunctivitis, episcleritis, uveitis, papilledema, pleuritis, pericarditis, aseptic peritonitis, early onset enterocolitis, hepatosplenomegaly, or lymphadenopathies
or present history of evidence of systemic inflammation (eg, elevation of
C-reactive protein [CRP] and/or erythrocyte sedimentation rate [ESR], anemia
thrombocytosis)
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
Has clinical signs or symptoms not explained by any other disorder (eg
Recurrent fevers that has gone undiagnosed after reasonable attempts, and that is consistent with the conditions under study in this protocol
infections, malignancies) and are consistent with a possible IFN-mediated
Panniculitis, ischemic ulcerative skin lesions, chilblain lesions, or livedo reticularis
autoinflammatory disease.1,36 Participants must meet both of the following
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
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
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.)
Has clinical signs or symptoms consistent with an undifferentiated
autoinflammatory disease (including but not limited to dysregulation in other
Be related by blood to an affected participant
proinflammatory cytokines such as IL-17, TNF, IL-18, and others). Participants
Is willing to allow storage of biological samples for future use in medical research
must meet one of the following criteria
Is willing to allow genetic testing on collected biological samples
Does not fulfill any of inclusion criterion #5 for affected participants
INCLUSION CRITERIA - HEALTHY VOLUNTEERS
Individuals with defined organ inflammation associated with past or current evidence of systemic inflammation
Is able to provide informed consent
Be at least 18 years old
Alternatively to #5, had been enrolled in the past as an affected participant on
Not be related to an affected participant
NIAMS study 03-AR-0173 and or had samples collected on 03-AR-0173
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
Is willing to allow genetic testing on collected biological samples

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
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note