NCT02974595

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

Recruiting now Last updated 6 April 2026

What this trial tests

trial in NOMID in 3,200 participants. Currently enrolling.

Timeline

9 December 2016

Primary endpoint
31 August 2031

30 September 2032

Quick facts

Lead sponsor	National Institute of Allergy and Infectious Diseases (NIAID)
Status	Recruiting now
Study type	OBSERVATIONAL
Enrollment	3,200
Start date	9 December 2016
Primary completion	31 August 2031
Estimated completion	30 September 2032
Sites	1 location across United States

Conditions studied

• NOMID — all drugs for NOMID →
• DIRA — all drugs for DIRA →
• NLRC4-MAS — all drugs for NLRC4-MAS →
• SAVI — all drugs for SAVI →

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Who can join

Under 99, any sex, with NOMID or DIRA. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. JAK1/2 inhibition with baricitinib in the treatment of autoinflammatory interferonopathies.
   Sanchez GAM, Reinhardt A, Ramsey S, Wittkowski H, et al · · 2018 · cited 377× · PMID 29649002 · DOI 10.1172/jci98814
2. An immune-based biomarker signature is associated with mortality in COVID-19 patients.
   Abers MS, Delmonte OM, Ricotta EE, Fintzi J, et al · · 2021 · cited 282× · PMID 33232303 · DOI 10.1172/jci.insight.144455
3. Nrf2 negatively regulates STING indicating a link between antiviral sensing and metabolic reprogramming.
   Olagnier D, Brandtoft AM, Gunderstofte C, Villadsen NL, et al · · 2018 · cited 240× · PMID 30158636 · DOI 10.1038/s41467-018-05861-7
4. Nitro-fatty acids are formed in response to virus infection and are potent inhibitors of STING palmitoylation and signaling.
   Hansen AL, Buchan GJ, Rühl M, Mukai K, et al · · 2018 · cited 238× · PMID 30061387 · DOI 10.1073/pnas.1806239115
5. Emerging Topical and Systemic JAK Inhibitors in Dermatology.
   Solimani F, Meier K, Ghoreschi K. · · 2019 · cited 199× · PMID 31849996 · DOI 10.3389/fimmu.2019.02847
6. Distinct interferon signatures and cytokine patterns define additional systemic autoinflammatory diseases.
   de Jesus AA, Hou Y, Brooks S, Malle L, et al · · 2020 · cited 179× · PMID 31874111 · DOI 10.1172/jci129301
7. Development of a Validated Interferon Score Using NanoString Technology.
   Kim H, de Jesus AA, Brooks SR, Liu Y, et al · · 2018 · cited 139× · PMID 29638206 · DOI 10.1089/jir.2017.0127
8. Novel proteasome assembly chaperone mutations in PSMG2/PAC2 cause the autoinflammatory interferonopathy CANDLE/PRAAS4.
   de Jesus AA, Brehm A, VanTries R, Pillet P, et al · · 2019 · cited 90× · PMID 30664889 · DOI 10.1016/j.jaci.2018.12.1012