Behavioral Manifestations of Lesch-Nyhan DiseasePhase 2/3NCT00935753
Trial of Kuvan in Lesch-Nyhan Disease
A Phase 2/3 study testing sapropterin in people with Behavioral Manifestations of Lesch-Nyhan Disease, run by University of California, San Diego at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 4 years and older
- Conditions the study is for
- Behavioral Manifestations of Lesch-Nyhan Disease
- What is being tested?
- sapropterin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2009to Feb 2010
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Ages 4 years and older
- Must have documented evidence of HPRT deficiency.
- Be on a stable treatment regimen for 30 days or more
- Willing and able to travel to San Diego for the study visits
- 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
Who cannot join
- Concurrent enrollment in an investigational drug study
- Currently taking levodopa
- Elevated liver enzymes
- Renal or liver impairment or disease
- Inability to comply with required study procedures
Trial locations and contacts
1 site in 1 country.
United States1 site
UCSD Mitochondrial and Metabolic Disease Center
San Diego, California, 92103
About this study
Official title: 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.
Read the 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.
- Being tested
- sapropterin
- Keywords
- Lesch-Nyhan Disease, self-mutilating behavior
- Medical subject headings
- Lesch-Nyhan Syndrome, Self-Injurious Behavior
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sapropterinDrug
oral 100mg tablets taken intact or dissolved in water or apple juice with morning meal for up to 60 days
| Study group | Role | What they receive |
|---|---|---|
| Kuvan | Experimental | 10mg/kg Kuvan for 5 days followed by 20mg/kg Kuvan for a total of 60 days Receives: Drug: sapropterin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Periodically during the eight weeks of treatment per patient
Secondary outcomes (1)
Effect of Kuvan on standard chemistries, plasma amino acids, and plasma and urinary catecholamines
Measured: Assessed periodically during treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2009 (estimated)
- Study startApr 2009
- Primary completionFeb 2010
- Study completionFeb 2010
Why it stopped: Contractual issues
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Behavioral Manifestations of Lesch-Nyhan DiseaseStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- BioMarin Pharmaceutical
- Responsible party
- Sponsor
- Investigators
- William L Nyhan, MD, PhD, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00935753
- Sponsor's protocol ID
- WLN01
- Status last verified
- Jul 2019
- First submitted
- 8 Jul 2009
- Last updated
- 2 Aug 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Trial of Kuvan™ (Sapropterin) Treatment in Patients With Lesch Nyhan Disease
- ClinicalTrials.gov ID
- NCT00935753
- Acronym / sponsor ID
- WLN01
- Keywords
- Lesch-Nyhan Disease, self-mutilating behavior
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Contractual issues
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- BioMarin Pharmaceutical
- Study start
- Apr 2009 (actual)
- Primary completion
- Feb 2010 (actual)
- Study completion
- Feb 2010 (actual)
- First posted
- 9 Jul 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Kuvan | Experimental | Drug: sapropterin10mg/kg Kuvan for 5 days followed by 20mg/kg Kuvan for a total of 60 days |
Who may qualify
- Ages
- 4 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Ages 4 years and older
- Must have documented evidence of HPRT deficiency.
- Be on a stable treatment regimen for 30 days or more
- Willing and able to travel to San Diego for the study visits
- 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
Key exclusion criteria (5 listed)
- Concurrent enrollment in an investigational drug study
- Currently taking levodopa
- Elevated liver enzymes
- Renal or liver impairment or disease
- Inability to comply with required study procedures
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sapropterinoral 100mg tablets taken intact or dissolved in water or apple juice with morning meal for up to 60 days | Drug | Kuvan |
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
1 secondary outcome
Effect of Kuvan on standard chemistries, plasma amino acids, and plasma and urinary catecholamines
Time frame: Assessed periodically during treatment
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2019.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William L Nyhan, MD, PhD principal investigator
University of California, San Diego
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing sapropterin in people with Behavioral Manifestations of Lesch-Nyhan Disease, run by University of California, San Diego at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 2 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2019; AzTrials last refreshed its copy on 7 Nov 2026.