Nervous System Malformations clinical trials

Anakinra to Treat Patients With Neonatal Onset Multisystem Inflammatory Disease

This study will evaluate the safety and effectiveness of anakinra (Kineret ) for treating patients with neonatal onset multisystem inflammatory disease (NOMID), also known as chronic infantile neurological, cutaneous and arthropathy (CINCA) syndrome. This disease can cause rash, joint deformities, brain inflammation, eye problems, and learning difficulties. Immune suppressing medicines commonly used to treat NOMID do not completely get rid of the disease symptoms and, if used for a long time in high doses, can cause harmful side effects. Anakinra, approved by The Food and Drug Administration for treating rheumatoid arthritis in adults, blocks a substance called IL-1 that may be an important factor in causing the inflammation in NOMID. Patients 2 years of age and older with NOMID whose disease symptoms appeared by at least 6 months of age may be eligible for this study. During a 3-week observation before beginning medication, patients will have a physical examination and evaluation of their condition. They will keep a daily diary of symptoms ratings, and will have blood drawn once a week to measure inflammation and monitor disease. At the end of this period, patients will be admitted to the NIH Clinical Center for 5 days to start daily anakinra injections, given under the skin of the thigh, upper arm, or belly. They will also be taught how to self-inject the medication. After 3 months on medication, patients will be randomly assigned to: 1) continue taking anakinra, or 2) receive a placebo injection (an inactive substance identical in appearance to the study drug). Follow-up visits at NIH for 5 days each will be scheduled at 1, 3, and 12 months, plus one visit between months 5 and 7. During this time, patients will undergo the following procedures: - Magnetic resonance imaging (MRI) scans of the brain and of affected joints. This test uses a magnetic field and radio waves to image the parts of the body under study. Patients who cannot lie still during the brain scan will be sedated. Only patients who do not require sedation will have their joints scanned. - Lumbar puncture (spinal tap). A local anesthetic is given and a needle is inserted in the space between the bones in the lower back where the cerebrospinal fluid circulates below the spinal cord. A small amount of fluid is collected through the needle for analysis. - Examinations by specialists, including an ophthalmologist (eye exam); otolaryngologist (ear, nose and throat exam and hearing test); neurologist (evaluate neurological symptoms such as headache, weakness, walking difficulties, blurred vision); dermatologist (skin exam with photography for record of rashes and joint changes); psychologist or psychiatrist (test memory and learning ability); rehabilitation medicine specialist (evaluate ability walk, move, and use the hands); speech therapist (evaluate ability to talk). - X-rays of joints and bones to look for changes during treatment with anakinra. - DEXA scan to examine bone density. - Blood samples to assess overall clinical condition, measure blood levels of anakinra, and - with the patient's agreement - to perform DNA studies to look for gene differences associated with NOMID. - Skin biopsy (optional) to examine how gene differences in NOMID are related to the rash. - Quality of life questionnaires and review of symptom ratings diaries. Between NIH visits, patients will be evaluated by their local doctor once a month for a checkup, blood tests, symptoms review, evaluation of drug side effects, and completion of quality of life questionnaires.