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

Launched by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID) · Nov 23, 2016

Keywords

ClinConnect Summary

This clinical trial is focused on understanding various autoinflammatory diseases, such as NOMID, DIRA, CANDLE, SAVI, and NLRC4-MAS. These conditions cause chronic inflammation in the body, leading to symptoms like fevers, rashes, and pain. Researchers aim to uncover the genetic causes and immune system issues behind these diseases, which could help develop better treatments and improve outcomes for patients in the future.

To participate in the trial, individuals aged 2 to 99 who have been diagnosed with one of the specific autoinflammatory diseases or have symptoms that suggest they might have one can apply. The trial also includes healthy volunteers and family members of affected individuals. Participants will undergo a thorough evaluation at the NIH, which includes medical history, physical exams, blood tests, and possibly imaging studies. They may also fill out questionnaires about their health. Depending on their condition, some participants may return for follow-up visits over a span of up to 15 years. This trial is currently recruiting and offers a chance to contribute to important research that could improve treatment for these complex diseases.

Gender

ALL

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 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.
• • 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, 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.
• 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 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.)
• • 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.
• • 6. Is able to provide informed consent.
• 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.
• • 6. Is able to provide informed consent.
• 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.