Trial of Kuvan in Lesch-Nyhan Disease

This study has been withdrawn prior to enrollment.
(Contractual issues)
Sponsor:
Collaborator:
BioMarin Pharmaceutical
Information provided by:
University of California, San Diego
ClinicalTrials.gov Identifier:
NCT00935753
First received: July 8, 2009
Last updated: March 15, 2010
Last verified: March 2010
  Purpose

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.


Condition Intervention Phase
Behavioral Manifestations of Lesch-Nyhan Disease
Drug: sapropterin
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Trial of Kuvan™ (Sapropterin) Treatment in Patients With Lesch Nyhan Disease

Resource links provided by NLM:


Further study details as provided by University of California, San Diego:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Effect of Kuvan on standard chemistries, plasma amino acids, and plasma and urinary catecholamines [ Time Frame: Assessed periodically during treatment ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 8
Arms Assigned Interventions
Experimental: Kuvan
10mg/kg Kuvan for 5 days followed by 20mg/kg Kuvan for a total of 60 days
Drug: sapropterin
oral 100mg tablets taken intact or dissolved in water or apple juice with morning meal for up to 60 days

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   4 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00935753

Locations
United States, California
UCSD Mitochondrial and Metabolic Disease Center
San Diego, California, United States, 92103
Sponsors and Collaborators
University of California, San Diego
BioMarin Pharmaceutical
Investigators
Principal Investigator: William L Nyhan, MD, PhD University of California, San Diego
  More Information

No publications provided

Responsible Party: William Leo Nyhan, M.D., Ph.D., Research Professor, University of California San Diego
ClinicalTrials.gov Identifier: NCT00935753     History of Changes
Other Study ID Numbers: WLN01
Study First Received: July 8, 2009
Last Updated: March 15, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, San Diego:
Lesch-Nyhan Disease
self-mutilating behavior

Additional relevant MeSH terms:
Lesch-Nyhan Syndrome
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Mental Retardation, X-Linked
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Metabolism, Inborn Errors
Purine-Pyrimidine Metabolism, Inborn Errors
Metabolic Diseases

ClinicalTrials.gov processed this record on September 18, 2014