Natural History and Cause of Neonatal Onset Multisystem Inflammatory Disease - Full Text View

Sponsored by:	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Information provided by:	National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:	NCT00059748

Purpose

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.

Condition
Urticaria Arthropathy Lymphadenopathy Nervous System Anomalies

MedlinePlus related topics: Hives Joint Disorders Rashes X-Rays

U.S. FDA Resources

Study Type:	Observational
Official Title:	NOMID/CAPS, DIRA, CRMO, Still's Disease, Behcet's Disease, and Other Undifferentiated Autoinflammatory Diseases

Further study details as provided by National Institutes of Health Clinical Center (CC):

Study Start Date:

April 2003

Detailed Description:

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 plan to extend this protocol to explore additional rare diseases including 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.

Eligibility

Ages Eligible for Study:	3 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.
A pediatric patient needs to be willing to assent to the protocol whenever possible.

Relatives of patients with autoinflammatory diseases may be included for genetic testing in collaboration with Dr. Daniel Kastner's laboratory.

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00059748

Contacts

Contact: Patient Recruitment and Public Liaison Office	(800) 411-1222	prpl@mail.cc.nih.gov
Contact: TTY	1-866-411-1010

Locations

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike	Recruiting
Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page This link exits the ClinicalTrials.gov site

Publications:

Hashkes PJ, Lovell DJ. Recognition of infantile-onset multisystem inflammatory disease as a unique entity. J Pediatr. 1997 Apr;130(4):513-5. No abstract available.

Sadiq SA, Gregson RM, Downes RN. The CINCA syndrome: a rare cause of uveitis in childhood. J Pediatr Ophthalmol Strabismus. 1996 Jan-Feb;33(1):59-63. No abstract available.

Miura M, Okabe T, Tsubata S, Takizawa N, Sawaguchi T. Chronic infantile neurological cutaneous articular syndrome in a patient from Japan. Eur J Pediatr. 1997 Aug;156(8):624-6.

Study ID Numbers:	030173, 03-AR-0173
Study First Received:	May 5, 2003
Last Updated:	April 24, 2009
ClinicalTrials.gov Identifier:	NCT00059748 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):

Central Nervous System Abnormalities
Arthropathy
Urticaria
Papilledema

Auto Inflammation
Neonatal Onset Multisystem Imflammatory
Disease
NOMID

Study placed in the following topic categories:

Papilledema
Skin Diseases
Nervous System Malformations
Joint Diseases
Urticaria
Inflammation
Behcet Syndrome

Lymphatic Diseases
Hypersensitivity
Still's Disease
Musculoskeletal Diseases
Hypersensitivity, Immediate
Congenital Abnormalities
Chronic, Infantile, Neurological, Cutaneous, Articular Syndrome

Additional relevant MeSH terms:

Lymphatic Diseases
Hypersensitivity
Skin Diseases, Vascular
Immune System Diseases
Skin Diseases
Musculoskeletal Diseases

Nervous System Malformations
Joint Diseases
Nervous System Diseases
Hypersensitivity, Immediate
Urticaria
Congenital Abnormalities

ClinicalTrials.gov processed this record on May 07, 2009