Clinical Trial: Trial of Kuvan in Lesch-Nyhan Disease
Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional
Official Title: Trial of Kuvan™ (Sapropterin) Treatment in Patients With Lesch Nyhan Disease
Brief Summary: To assess the possibility that treatment with Kuvan (a form of tetrahydrobiopterin) will lessen the abnormal behavior and/or neurology commonly found in Lesch-Nyhan disease (LND); to assess biochemical changes as measured in blood and urine.
Detailed Summary:
Lesch-Nyhan disease (LND) is an X-linked disorder of purine metabolism which results from mutation in the gene for the enzyme hypoxanthineguanine phosphoribosyltransferase (HPRT); patients have hyperuricemia, gout, urinary tract calculi, and nephropathy which are effectively treated with allopurinol. There is also a syndrome of dystonia, chorea and athetosis, as well as involuntary self mutilative biting and aggression toward their caretakers, for which there is no treatment.
Kuvan™ is a form of tetrahydrobiopterin (BH4), and is approved to help lower the blood levels of phenylalanine in people who have phenylketonuria (PKU). LND patients have been found to have decreased BH4 in the spinal fluid and brain; BH4 is a precursor of dopamine, which has an effect on behavior. In an earlier study Dr Nyhan found that treatment of LND with 5-hydroxytryptophan and carbidopa abolished the self-injurious behavior but was uniformly transient.
This is a single site open-label protocol for eight subjects age 4 years and older with Lesch-Nyhan Disease documented by deficiency of HPRT.
The study involves three study visits to San Diego and one study visit done locally. The first visit will last 13 days, the following visits are single day visits at week 4 and week 8, and the local study visit is a brief outpatient visit at week 6. Physical and neurological exams, videotaping of the patient's interactions with the study staff, and blood and urine collection for laboratory analyses will be performed at each San Diego visit. A family member or caregiver will be asked to complete a short assessment form and report any illness or medication changes. In addition, the study staff will have weekly telephone contact with the family to discuss any behavioral changes or study drug issues.
Current Primary Outcome: Clinical responses to be monitored will include frequency and severity of self mutilation episodes, frequency and severity of aggressive acts towards others, and any effect on involuntary movements. [ Time Frame: Periodically during the eight weeks of treatment per patient ]
Original Primary Outcome: Same as current
Current Secondary Outcome: Effect of Kuvan on standard chemistries, plasma amino acids, and plasma and urinary catecholamines [ Time Frame: Assessed periodically during treatment ]
Original Secondary Outcome: Same as current
Information By: University of California, San Diego
Dates:
Date Received: July 8, 2009
Date Started:
Date Completion:
Last Updated: March 15, 2010
Last Verified: March 2010
