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 |
|---|---|
| Healthy: | No |
| Age Range: | Any - 99 |
| Updated: | 3/13/2019 |
| Start Date: | November 23, 2016 |
| End Date: | October 20, 2032 |
| Contact: | Raphaela T Goldbach-Mansky, M.D. |
| Email: | goldbacr@mail.nih.gov |
| Phone: | (301) 761-7553 |
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)
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.
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.
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.
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.
- INCLUSION CRITERIA - AFFECTED PARTICIPANTS:
1. Be 3 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 not be seen at the NIH CC.)
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 3 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.
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.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
301-496-2563
Phone: 800-411-1222
National Institutes of Health Clinical Center The National Institutes of Health (NIH) Clinical Center in...
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