Trial of Kuvan in Lesch-Nyhan Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00935753
Recruitment Status : Withdrawn (Contractual issues)
First Posted : July 9, 2009
Last Update Posted : March 16, 2010
BioMarin Pharmaceutical
Information provided by:
University of California, San Diego

July 8, 2009
July 9, 2009
March 16, 2010
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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 ]
Same as current
Complete list of historical versions of study NCT00935753 on Archive Site
Effect of Kuvan on standard chemistries, plasma amino acids, and plasma and urinary catecholamines [ Time Frame: Assessed periodically during treatment ]
Same as current
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Trial of Kuvan in Lesch-Nyhan Disease
Trial of Kuvan™ (Sapropterin) Treatment in Patients With Lesch Nyhan Disease
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.

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.

If the patient's self injurious behavior becomes worse after starting Kuvan the drug will be discontinued and the patient will be followed until the behavior returns to baseline.

Phase 2
Phase 3
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Behavioral Manifestations of Lesch-Nyhan Disease
Drug: sapropterin
oral 100mg tablets taken intact or dissolved in water or apple juice with morning meal for up to 60 days
Experimental: Kuvan
10mg/kg Kuvan for 5 days followed by 20mg/kg Kuvan for a total of 60 days
Intervention: Drug: sapropterin
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Same as current
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Inclusion Criteria:

  1. Ages 4 years and older
  2. Must have documented evidence of HPRT deficiency.
  3. Be on a stable treatment regimen for 30 days or more
  4. Willing and able to travel to San Diego for the study visits
  5. Have a local neurologist or physician familiar with the patient or experienced in managing behavioral/neuromuscular disorders and willing to assist with study procedures and adverse events if necessary

Exclusion Criteria:

  1. Concurrent enrollment in an investigational drug study
  2. Currently taking levodopa
  3. Elevated liver enzymes
  4. Renal or liver impairment or disease
  5. Inability to comply with required study procedures
Sexes Eligible for Study: All
4 Years and older   (Child, Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
United States
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William Leo Nyhan, M.D., Ph.D., Research Professor, University of California San Diego
University of California, San Diego
BioMarin Pharmaceutical
Principal Investigator: William L Nyhan, MD, PhD University of California, San Diego
University of California, San Diego
March 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP