Autism Spectrum DisorderNCT01141595
Tetrahydrobiopterin Treatment in Children With Idiopathic Cognitive Developmental Disorders
A study testing sapropterin dihydrochloride in people with Autism Spectrum Disorder, run by The University of Texas Health Science Center, Houston at 1 site in United States.
Trial summary
The purpose of this study is to develop biomarkers for central nervous system BH4 concentration in children with autism so they can be easily screened to determine if they may benefit from BH4 supplementation. Kuvan is a synthetic form of BH4. Read more about this study
- Who is it for?
- Ages 2 to 6 years
- Conditions the study is for
- Autism Spectrum Disorder
- What is being tested?
- sapropterin dihydrochloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2010to Sep 2011
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 2 to 6 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Children 2 years 0 months to 6 years 11 months of age will be recruited.
- Delay in language and/or social development with or without delays in gross and/or fine motor development.
- CSF BH4 level less than or equal to 30 nM/L as determined by lumbar puncture.
- Adaptive Behavior greater than 50 as determined by the Vineland Adaptive Behavior Scale.
Who cannot join
- Epilepsy / Seizure disorder as determined by medical history.
- Epileptiform discharges without clinical seizures.
- Metabolic disorder that would be a contraindication to tetrahydrobiopterin treatment.
- Genetic disorder
- Therapies that cannot be maintained at a constant level or have not been ongoing for more than 3 months as determined by medical history
- Prematurity
Show all 13Show fewer
- Developmental delay isolated to motor delay.
- Current gastroesophageal reflux
- Current or history of liver or kidney disease
- Severe irritability (as determined by the aberrant behavior checklist)
- Drugs known to affect folate metabolism (e.g., methotrexate) and their derivatives
- Patients who are receiving drugs that affect nitric oxide-mediated vasorelaxation (e.g., PDE-5 inhibitors such as sildenafil, vardenafil, or tadalafil)
- Patients who are receiving levodopa.
Trial locations and contacts
1 site in 1 country.
United States1 site
Arkansas Children's Hospital Research Institute
Little Rock, Arkansas, 72202
About this study
Official title: Biomarkers of Central Nervous System Tetrahydrobiopterin Concentration and Response to Tetrahydrobiopterin Supplementation in Children With Idiopathic Cognitive Developmental Disorders
The purpose of this study is to develop biomarkers for central nervous system BH4 concentration in children with autism so they can be easily screened to determine if they may benefit from BH4 supplementation. Kuvan is a synthetic form of BH4. BH4 is an enzyme cofactor that is essential for several critical metabolic functions.
Read the detailed description
SUMMARY
PURPOSE: The purpose of this study is to develop biomarkers for central nervous system BH4 concentration in children with autism so they can be easily screened to determine if they may benefit from BH4 supplementation. Kuvan is a synthetic form of BH4. BH4 is an enzyme cofactor that is essential for several critical metabolic functions.
Procedures: Consented subjects' behavior, particularly irritability, cognitive and language function will be assessed at baseline to make sure that the subject meets the inclusion and exclusion criteria. Parents of subjects will be instructed to give the subjects 20 mg/kg/day of Kuvan® orally dissolved in 4 - 8oz. of water or apple juice with breakfast. Subjects will not be permitted to start any new supplement treatments during the study period but will be allowed to continue previous supplements. Subjects will be permitted to take over the counter medications or other prescription medications for acute illnesses. Evaluation of subjects will include three clinic visits for neuropsychological and clinical testing, completion of study-related questionnaires and telephone follow-up visits.
Course of Study: Subjects will be in the study for up to 16 weeks.
Enrollment: The study will enroll 20 (male and female) subjects, 2-6 years old, with delays in language and/or social development. Vulnerable populations include children. A pediatric risk assessment was completed by Ian Butler, MD with an outcome of minimum risks to subjects.
Recruitment: Subjects will be recruited when their parents present them for care at the University of Texas medically-based autism clinic.
Known Risks: For the study drug Kuvan, there have been rare associations with gastroesophageal reflux and a previous form of this compound was associated with seizures in individuals taking Levodopa concurrently. There is a risk of loss of confidentiality.
Data Safety Monitoring: A DSMB will not be formed for this study. The PI will be responsible for the data and safety of the study.
Informed Consent: A written parental informed consent form has been submitted for review and approval. There is no cost for participation, and no remuneration. Confidentiality will be maintained through the use of unique study codes.
IND#: A request for a pre-IND meeting with the FDA to discuss the possible IND exemption has been submitted.
Funding Source: This study is being funded by BioMarin Pharmaceuticals.
SCIENTIFIC PRE-REVIEW: The Clinical Research Unit Review Board Committee Scientific Advisory Committee (SAC) completed the submission with the outcome of CRU - Approved on12/10/2009.
- Conditions
- Autism Spectrum Disorder
- Being tested
- sapropterin dihydrochloride
- Medical subject headings
- Autism Spectrum Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sapropterin dihydrochlorideDrug
Also called Kuvan®
Patients will be instructed to take 20 mg/kg/day of Kuvan® orally dissolved in 4 - 8oz. of water or apple juice with breakfast.
| Study group | Role | What they receive |
|---|---|---|
| Kuvan® | Experimental | Patients will be instructed to take 20 mg/kg/day of Kuvan® orally dissolved in 4 - 8oz. of water or apple juice with breakfast. Receives: Drug: sapropterin dihydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Preschool Language Scales
Change in the raw score from baseline of the Preschool Language Scales over the 16 week period. The raw score was measured at baseline, 8 weeks and 16 weeks after starting treatment and the change over the 16 week period from baseline to the end of the study was calculated. There was no imputed data and the analysis was as treated. The raw score ranged from 0 to 130. Higher scores indicate better performance.
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2010 (estimated)
- Study startJul 2010
- Primary completionSep 2011
- Study completionSep 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Autism Spectrum DisorderStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center, HoustonThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- BioMarin Pharmaceutical
- Responsible party
- Principal investigator, Richard Frye, Arkansas Children's Hospital Research Institute
- Investigators
- Richard E Frye, MD, Principal investigator, Arkansas Children's Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01141595
- Sponsor's protocol ID
- HSC-MS-09-0578
- Status last verified
- Feb 2014
- First submitted
- 8 Jun 2010
- Last updated
- 1 Apr 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Frye RE, Huffman LC, Elliott GR. Tetrahydrobiopterin as a novel therapeutic intervention for autism. Neurotherapeutics. 2010 Jul;7(3):241-9. doi: 10.1016/j.nurt.2010.05.004.
PubMed 20643376Frye RE. Central tetrahydrobiopterin concentration in neurodevelopmental disorders. Front Neurosci. 2010 Jul 8;4:52. doi: 10.3389/fnins.2010.00052. eCollection 2010.
PubMed 20661295Frye RE, DeLatorre R, Taylor HB, Slattery J, Melnyk S, Chowdhury N, James SJ. Metabolic effects of sapropterin treatment in autism spectrum disorder: a preliminary study. Transl Psychiatry. 2013 Mar 5;3(3):e237. doi: 10.1038/tp.2013.14.
PubMed 23462988
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biomarkers of Central Nervous System Tetrahydrobiopterin Concentration and Response to Tetrahydrobiopterin Supplementation in Children With Idiopathic Cognitive Developmental Disorders
- ClinicalTrials.gov ID
- NCT01141595
- Acronym / sponsor ID
- HSC-MS-09-0578
- Conditions
- Autism Spectrum Disorder
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center, HoustonUniversity, hospital or other
- Collaborators
- BioMarin Pharmaceutical
- Study start
- Jul 2010
- Primary completion
- Sep 2011 (actual)
- Study completion
- Sep 2011 (actual)
- First posted
- 10 Jun 2010 (estimated)
- Results
- Posted 24 Feb 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to develop biomarkers for central nervous system BH4 concentration in children with autism so they can be easily screened to determine if they may benefit from BH4 supplementation. Kuvan is a synthetic form of BH4. BH4 is an enzyme cofactor that is essential for several critical metabolic functions.
Detailed description
SUMMARY
PURPOSE: The purpose of this study is to develop biomarkers for central nervous system BH4 concentration in children with autism so they can be easily screened to determine if they may benefit from BH4 supplementation. Kuvan is a synthetic form of BH4. BH4 is an enzyme cofactor that is essential for several critical metabolic functions.
Procedures: Consented subjects' behavior, particularly irritability, cognitive and language function will be assessed at baseline to make sure that the subject meets the inclusion and exclusion criteria. Parents of subjects will be instructed to give the subjects 20 mg/kg/day of Kuvan® orally dissolved in 4 - 8oz. of water or apple juice with breakfast. Subjects will not be permitted to start any new supplement treatments during the study period but will be allowed to continue previous supplements. Subjects will be permitted to take over the counter medications or other prescription medications for acute illnesses. Evaluation of subjects will include three clinic visits for neuropsychological and clinical testing, completion of study-related questionnaires and telephone follow-up visits.
Course of Study: Subjects will be in the study for up to 16 weeks.
Enrollment: The study will enroll 20 (male and female) subjects, 2-6 years old, with delays in language and/or social development. Vulnerable populations include children. A pediatric risk assessment was completed by Ian Butler, MD with an outcome of minimum risks to subjects.
Recruitment: Subjects will be recruited when their parents present them for care at the University of Texas medically-based autism clinic.
Known Risks: For the study drug Kuvan, there have been rare associations with gastroesophageal reflux and a previous form of this compound was associated with seizures in individuals taking Levodopa concurrently. There is a risk of loss of confidentiality.
Data Safety Monitoring: A DSMB will not be formed for this study. The PI will be responsible for the data and safety of the study.
Informed Consent: A written parental informed consent form has been submitted for review and approval. There is no cost for participation, and no remuneration. Confidentiality will be maintained through the use of unique study codes.
IND#: A request for a pre-IND meeting with the FDA to discuss the possible IND exemption has been submitted.
Funding Source: This study is being funded by BioMarin Pharmaceuticals.
SCIENTIFIC PRE-REVIEW: The Clinical Research Unit Review Board Committee Scientific Advisory Committee (SAC) completed the submission with the outcome of CRU - Approved on12/10/2009.
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: sapropterin dihydrochloridePatients will be instructed to take 20 mg/kg/day of Kuvan® orally dissolved in 4 - 8oz. of water or apple juice with breakfast. |
Who may qualify
- Ages
- 2 to 6 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Children 2 years 0 months to 6 years 11 months of age will be recruited.
- Delay in language and/or social development with or without delays in gross and/or fine motor development.
- CSF BH4 level less than or equal to 30 nM/L as determined by lumbar puncture.
- Adaptive Behavior greater than 50 as determined by the Vineland Adaptive Behavior Scale.
Key exclusion criteria (13 listed)
- Epilepsy / Seizure disorder as determined by medical history.
- Epileptiform discharges without clinical seizures.
- Metabolic disorder that would be a contraindication to tetrahydrobiopterin treatment.
- Genetic disorder
- Therapies that cannot be maintained at a constant level or have not been ongoing for more than 3 months as determined by medical history
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 |
|---|---|---|
| sapropterin dihydrochlorideAlso: Kuvan®Patients will be instructed to take 20 mg/kg/day of Kuvan® orally dissolved in 4 - 8oz. of water or apple juice with breakfast. | Drug | Kuvan® |
Primary outcome
Preschool Language Scales
Time frame: 16 weeks
Change in the raw score from baseline of the Preschool Language Scales over the 16 week period. The raw score was measured at baseline, 8 weeks and 16 weeks after starting treatment and the change over the 16 week period from baseline to the end of the study was calculated. There was no imputed data and the analysis was as treated. The raw score ranged from 0 to 130. Higher scores indicate better performance.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 20643376Frye RE, Huffman LC, Elliott GR. Tetrahydrobiopterin as a novel therapeutic intervention for autism. Neurotherapeutics. 2010 Jul;7(3):241-9. doi: 10.1016/j.nurt.2010.05.004.
- Background: PubMed 20661295Frye RE. Central tetrahydrobiopterin concentration in neurodevelopmental disorders. Front Neurosci. 2010 Jul 8;4:52. doi: 10.3389/fnins.2010.00052. eCollection 2010.
- Results publication: PubMed 23462988Frye RE, DeLatorre R, Taylor HB, Slattery J, Melnyk S, Chowdhury N, James SJ. Metabolic effects of sapropterin treatment in autism spectrum disorder: a preliminary study. Transl Psychiatry. 2013 Mar 5;3(3):e237. doi: 10.1038/tp.2013.14.
- Manuscript of Study ResultsLink provided by the sponsor.
Related trials for Autism Spectrum Disorder
RecruitingPhase 1
Cannabidiol (CBD) in Adults With ASD
Autism Spectrum Disorder
RecruitingPhase 3
A Study to Evaluate the Long-term Safety and Tolerability of Xanomeline and Trospium Chloride for the Treatment of Psychiatric Disorders in Children and Adolescents
Schizophrenia, Autism-Related Irritability
Not yet recruiting
Sensory-integration Therapy Verses Augumented Reality-based Training in ASD
Autism Spectrum Disorder
Recruiting
Cumulative and Booster Effects of Multisession Prefrontal tDCS in ASD Adolescents
Transcranial Direct Current Stimulation, Autistic Spectrum Disorder
Not yet recruiting
"Family Resilience And Mind-body Enhancement" (FRAME): A Randomised Controlled Trial
Autism
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.
Richard E Frye, MD principal investigator
Arkansas Children's Hospital Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing sapropterin dihydrochloride in people with Autism Spectrum Disorder, run by The University of Texas Health Science Center, Houston 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 4 inclusion and 13 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: finished, as of the sponsor's last update on 1 Apr 2014. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Feb 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Preschool Language Scales (time frame: 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01141595, which also lists 3 linked publications.
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 1 Apr 2014.