Studies of the Natural History, Pathogenesis, and Outcome of Autoinflammatory Diseases (NOMID/CAPS, DIRA, CANDLE, CRMO, Still's Disease, Behcet's Disease, and Other Undifferentiated Autoinflammatory Diseases)
| City: |
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Bethesda |
| State: |
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Maryland |
| Zip Code: |
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20892 |
| Conditions: |
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Urticaria - Arthropathy - Lymphadenopathy - Nervous System Anomalies |
| Purpose: |
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This study will examine and test patients with neonatal onset multi-system inflammatory
disease (NOMID) to learn more about the cause and course of the disease. It will study the
disease signs and symptoms and the possible role of a gene called CIAS1, and it will develop
a database to gather information on patients with NOMID in the United States and around the
world. It will also serve as a screening protocol to offer eligible patients participation
in a treatment protocol, if an appropriate one is available.
Patients with this rare disease usually develop a chronic rash in the first days to weeks of
life that can affect the entire body. Almost all patients have eye problems such as
inflammation, optic atrophy, or swelling of the optic nerve. Joint problems can lead to
severe disability. Nervous system problems can include chronic meningitis, brain atrophy,
seizures, mental retardation, migraine headaches, hearing loss and others.
Patients with NOMID whose symptoms include a rash since birth along with one of the
following: joint disease or bone overgrowth; central nervous system problem, eye problems,
enlarged liver and spleen, or elevated inflammatory markers (substances that indicate
inflammation) may be eligible for this study.
Participants will be admitted to the NIH Clinical Center for 3 to 4 days for the following
tests:
- Medical history and physical, neurological, and eye examinations.
- Hearing test.
- Completion of quality of life questionnaires.
- Evaluation of memory and learning ability.
- Urine test.
- Blood tests for genetic analysis, HIV infection, and other laboratory values.
- Blood test to evaluate growth hormones in order to learn more about how inflammation
affects the patient's growth. For this test, a small amount of blood is drawn every 20
minutes for 8 hours while the patient is sleeping. The tests show if the rhythm of
growth hormone and other substances in the body is normal. This test is optional.
- Lumbar puncture (spinal tap) to collect cerebrospinal fluid (CSF) from the spinal
canal. For this procedure, a local anesthetic is given and a needle is inserted in the
space between the bones in the lower back where the CSF circulates below the spinal
cord. A small amount of fluid is collected through the needle.
- Skin biopsy (surgical removal of tissue for microscopic examination) to characterize
the rash and learn more about what causes it. The biopsy area is numbed and the
superficial top layers of skin are shaved.
- Photographs of the patient in a bathing suit or underwear. These pictures are taken to
document the skin rash and joint changes.
- X-rays and magnetic resonance (MRI) scans of the knees or other affected joints.
X-rays will be done in patients who do not have recent x-rays (within the past 3
months) available. MRI will be done in patients who can lie in the scanner without
requiring sedation.
- Brain MRI to evaluate the central nervous system involvement, done only in patients who
can lie still for 45 minutes.
- Bone density scan to evaluate bone mineralization.
Rehabilitation evaluation to assess hand coordination, the ability to walk, and other
functions.
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| Study Summary: |
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Autoinflammatory multisystem diseases are a group of diseases that are characterized by
recurrent episodes of systemic inflammation as well as organ specific inflammation that can
involve the skin, eyes, joints, bones, serosal surfaces, inner ear, and brain. The
prominent role of IL-1 in the pathogenesis of these disorders has first become evident
through the discovery of mutations in CIAS1 causing the cryopyrin-associated periodic
syndromes (CAPS) including the most severe presentation Neonatal Onset Multisystem
Inflammatory Disease (NOMID). We recently identified a new autoinflammatory disease DIRA
(Deficiency of IL-1 Receptor Antagonist), a disease that is caused by mutations in IL1RN.
Therapy with anakinra, the IL-1 receptor antagonist, can be life-saving. We also study
additional rare diseases including CANDLE (chronic atypical neutrophilic dermatosis with
lipodystrophy and elevated temperatures), the spectrum CRMO (Chronic Recurrent Multifocal
Osteomyelitis), Still's disease, and Beh et's disease (BD) all of which may involve
dysregulation of IL-1. In this research protocol we seek to comprehensively evaluate
affected patients clinically, genetically, immunologically, and endocrinologically. In
addition we intend to evaluate long term outcome and biomarkers. Eligibility for ongoing and
planned treatment protocols will be determined by screening patients in this protocol. We
plan to evaluate patients on a consultative basis for other autoinflammatory diseases for
possible enrollment into this study.
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| Criteria: |
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- INCLUSION CRITERIA:
Subjects with known or suspected diagnosis of NOMID/CAPS, DIRA, CRMO, Still's disease,
Behcet's disease, and other autoinflammatory diseases will be evaluated either at the
outpatient or inpatient unit of the Clinical Center as indicated.
- Patients with NOMID/CAPS or DIRA, who are mutation positive for the disease or
fulfill clinical criteria of the disease.
- Patients who have non infectious osteolytic bone lesions
- Patients who fulfill criteria for definite or probable Still's disease
- Patients who fulfill criteria for definite or probable Behcet's disease
- Patients with other suspected autoinflammatory diseases
There is:
- No age limit
- Patients or their legal guardians need to be able and willing to give informed
consent and a pediatric patient needs to be willing to assent.
Relatives of patients with autoinflammatory diseases or healthy volunteers may be included
for genetic testing in collaboration with Dr. Daniel Kastner's laboratory. We may also
collect blood for serum and RNA analyses to establish a cohort of healthy controls that is
matched in age, gender, and ethnicity to the study patients.
EXCLUSION CRITERIA:
Active malignancy or any medical condition that in the opinion of the investigator would
warrant exclusion
Inability to provide consent
Inability to return for follow up visits
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| NCT ID: |
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NCT00059748 |
| Primary Contact: |
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Principal Investigator
Raphaela T Goldbach-Mansky, M.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Elaine M Novakovich
Phone: (301) 451-1450
Email: enovakovich@mail.cc.nih.gov
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| Backup Contact: |
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Email: goldbacr@exchange.nih.gov
Raphaela T Goldbach-Mansky, M.D.
Phone: (301) 435-6243
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| Location Contact: |
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Bethesda, Maryland 20892
United States
For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)
Phone: 800-411-1222
Email: prpl@mail.cc.nih.gov
Site Status: Recruiting |
| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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May 20, 2013 |
| Modifications to this listing: |
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