PhenylketonuriaPhase 1NCT00244218
Response to Phenylketonuria to Tetrahydrobiopterin (BH4)
A Phase 1 study testing tetrahydrobiopterin (BH4) in people with Phenylketonuria, run by The University of Texas Medical Branch, Galveston at 1 site in United States.
Trial summary
The purpose of this study is to determine whether tetrahydrobiopterin (BH4)is effective in treating patients with PKU. Read more about this study
- Who is it for?
- Ages 10 years and olderHealthy volunteers can take part
- Conditions the study is for
- Phenylketonuria
- What is being tested?
- tetrahydrobiopterin (BH4)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 57 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2005to Jan 2015
- Phase
- Phase 1
- 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 10 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Subject and/or parent or guardian must be capable of understanding and providing written informed consent
- Subjects must have Phenylketonuria (PKU)or hyperphenylalaninemia (HPA), defined as baseline blood Phe levels of >600 umol/L
- Subjects must be at least 10 years of age, and may be of either gender and any ethnic group
- Female subjects of childbearing potential must agree to use adequate birth control or refrain from sexual activity throughout study participation
Who cannot join
- Female subjects who are pregnant or breastfeeding
- Subjects who have concurrent diseases or conditions that require medication or treatment
- Subjects who require concomitant treatment with any drug known to inhibit folate synthesis
- Subjects who have been treated with any investigational drug within 30 days
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas Medical Branch
Galveston, Texas, 77555
About this study
The purpose of this study is to determine whether tetrahydrobiopterin (BH4)is effective in treating patients with PKU.
Read the detailed description
Phenylketonuria(PKU) is an autosomal recessive disorder caused by a defect in the enzyme phenylalanine hydroxylase(PAH). this incidence of PKU in the US is about 1:15,000 births. The disease is pan ethnic with more prevalence among individuals of European ancestry. Recently, a number of patients with PKU showed a marked decrease in their blood Phe levels when the cofactor for PAH, tetrahydrobiopterin (BH4) was given orally. All these patients had mutations in PAH while the metabolism of BH4 was normal. These observations were confirmed by several centers including a pilot study conducted in our institutions. In the study in our centers, we have identified 21 of 36 patients tested who responded favorably to BH4.
Recognizing the difficulties with phenylalanine restricted diet, an NIH Consensus Conference on PKU held in 1999, encouraged exploring different modalities for treating PKU, and BH4 is among these modalities. This proposal is a three year, double blind placebo control, multi-center study. An oral load of 10 mg/kg BH4 wil be given to patients with PKU to identify those that respond with lowering of blood Phe greater or equal to 30%. Blood Phe, tyrosine and dietary intake will be determined at zero time and 24 hours post load. From this group of BH4 responsive individuals, thirty-six will be enrolled in the double blind study. subjects will be randomized to the treatment of placebo group. Those who enter the trial will have zero time assessments including blood Phe and tyrosine, dietary intake, physical exam, kidney function, liver function and complete blood count (CBC). Phe and tyrosine and diet intakes, two prior to the study and the zero time, will be averaged and used as the baseline measures.
The subjects will be assigned randomly to take either 10mg/kg of BH4 orally or a placebo without BH4. Blood Phe, tyrosine and dietary intake will be obtained every other week throughout the 12 week study period. Liver function and kidney function and CBC's will be obtained monthly. Side effects will be evaluated and noted. Subjects will be instructed to record two day diet diaries prior to blood Phe sampling throughout the study. The NIH Consensus Report suggests maintaining blood Phe< 36 umol/l when less than 12 years of age or up to 900 umol/l after 12 years of age. These levels will be used to determine the efficacy end points of the study. At the end of three months, blood Phe and tyrosine, dietary intake, physical exam, kidney function, liver function and CBC will be performed. At this time efficacy of BH4 will be determined and all subjects will continue in an open label 12 weeks BH4 treatment, (10mg/kg/day), with assessments collected as in the first phase of the study. After the subject has had both phases they will be followed for an additional 3 months. The additional 3 month trial on BH4 will provide long term safety data from 18 subjects who took BH4 in both the first and second phase in a continuous fashion.
- Conditions
- Phenylketonuria
- Being tested
- tetrahydrobiopterin (BH4)
- Keywords
- phenylketonuria, hyperphenylalaninemia
- Medical subject headings
- Phenylketonurias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tetrahydrobiopterin (BH4)Drug
Also called BH4
Either placebo or tetrahydrobiopterin (BH4) , 10mg/kg/day will be given for three months. Then the patient will be given three additional months of open label BH4 at the same rate.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm | Experimental | Drug: tetrahydrobiopterin (BH4) Either placebo or BH4, 10mg/kg/day will be given for three months. Then the patient will be given three additional months of open label BH4 at the same rate. Receives: Drug: tetrahydrobiopterin (BH4) |
| Control Arm | Placebo comparator | Drug: tetrahydrobiopterin (BH4) Either placebo or BH4, 10mg/kg/day will be given for three months. Then the patient will be given three additional months of open label BH4 at the same rate. Receives: Drug: tetrahydrobiopterin (BH4) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood Phe level decrease by 30%
Measured: 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2005 (estimated)
- Study startApr 2005
- Primary completionMar 2009
- Study completionJan 2015
Why it stopped: The FDA has approved Kuvan (BH4) as a therapeutic agent for phenylketonuria
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PhenylketonuriaStudies of the same condition, open and under way.
- More trials run by The University of Texas Medical Branch, GalvestonThe 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Reuben Matalon, MD, PhD, Principal investigator, University of Texas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00244218
- Sponsor's protocol ID
- 01-269
- Other IDs
- FD-R-002600-01
- Status last verified
- Jun 2015
- First submitted
- 25 Oct 2005
- Last updated
- 21 Sep 2021
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Response to Phenylketonuria to Tetrahydrobiopterin (BH4)
- ClinicalTrials.gov ID
- NCT00244218
- Acronym / sponsor ID
- 01-269
- Conditions
- Phenylketonuria
- Keywords
- phenylketonuria, hyperphenylalaninemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The FDA has approved Kuvan (BH4) as a therapeutic agent for phenylketonuria
- Enrolment
- 57 participants (actual)
- Lead sponsor
- The University of Texas Medical Branch, GalvestonUniversity, hospital or other
- Study start
- Apr 2005
- Primary completion
- Mar 2009 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 26 Oct 2005 (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.
The purpose of this study is to determine whether tetrahydrobiopterin (BH4)is effective in treating patients with PKU.
Detailed description
Phenylketonuria(PKU) is an autosomal recessive disorder caused by a defect in the enzyme phenylalanine hydroxylase(PAH). this incidence of PKU in the US is about 1:15,000 births. The disease is pan ethnic with more prevalence among individuals of European ancestry. Recently, a number of patients with PKU showed a marked decrease in their blood Phe levels when the cofactor for PAH, tetrahydrobiopterin (BH4) was given orally. All these patients had mutations in PAH while the metabolism of BH4 was normal. These observations were confirmed by several centers including a pilot study conducted in our institutions. In the study in our centers, we have identified 21 of 36 patients tested who responded favorably to BH4.
Recognizing the difficulties with phenylalanine restricted diet, an NIH Consensus Conference on PKU held in 1999, encouraged exploring different modalities for treating PKU, and BH4 is among these modalities. This proposal is a three year, double blind placebo control, multi-center study. An oral load of 10 mg/kg BH4 wil be given to patients with PKU to identify those that respond with lowering of blood Phe greater or equal to 30%. Blood Phe, tyrosine and dietary intake will be determined at zero time and 24 hours post load. From this group of BH4 responsive individuals, thirty-six will be enrolled in the double blind study. subjects will be randomized to the treatment of placebo group. Those who enter the trial will have zero time assessments including blood Phe and tyrosine, dietary intake, physical exam, kidney function, liver function and complete blood count (CBC). Phe and tyrosine and diet intakes, two prior to the study and the zero time, will be averaged and used as the baseline measures.
The subjects will be assigned randomly to take either 10mg/kg of BH4 orally or a placebo without BH4. Blood Phe, tyrosine and dietary intake will be obtained every other week throughout the 12 week study period. Liver function and kidney function and CBC's will be obtained monthly. Side effects will be evaluated and noted. Subjects will be instructed to record two day diet diaries prior to blood Phe sampling throughout the study. The NIH Consensus Report suggests maintaining blood Phe< 36 umol/l when less than 12 years of age or up to 900 umol/l after 12 years of age. These levels will be used to determine the efficacy end points of the study. At the end of three months, blood Phe and tyrosine, dietary intake, physical exam, kidney function, liver function and CBC will be performed. At this time efficacy of BH4 will be determined and all subjects will continue in an open label 12 weeks BH4 treatment, (10mg/kg/day), with assessments collected as in the first phase of the study. After the subject has had both phases they will be followed for an additional 3 months. The additional 3 month trial on BH4 will provide long term safety data from 18 subjects who took BH4 in both the first and second phase in a continuous fashion.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm | Experimental | Drug: tetrahydrobiopterin (BH4)Drug: tetrahydrobiopterin (BH4) Either placebo or BH4, 10mg/kg/day will be given for three months. Then the patient will be given three additional months of open label BH4 at the same rate. |
| Control Arm | Placebo comparator | Drug: tetrahydrobiopterin (BH4)Drug: tetrahydrobiopterin (BH4) Either placebo or BH4, 10mg/kg/day will be given for three months. Then the patient will be given three additional months of open label BH4 at the same rate. |
Who may qualify
- Ages
- 10 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Subject and/or parent or guardian must be capable of understanding and providing written informed consent
- Subjects must have Phenylketonuria (PKU)or hyperphenylalaninemia (HPA), defined as baseline blood Phe levels of >600 umol/L
- Subjects must be at least 10 years of age, and may be of either gender and any ethnic group
- Female subjects of childbearing potential must agree to use adequate birth control or refrain from sexual activity throughout study participation
Key exclusion criteria (4 listed)
- Female subjects who are pregnant or breastfeeding
- Subjects who have concurrent diseases or conditions that require medication or treatment
- Subjects who require concomitant treatment with any drug known to inhibit folate synthesis
- Subjects who have been treated with any investigational drug within 30 days
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 |
|---|---|---|
| tetrahydrobiopterin (BH4)Also: BH4Either placebo or tetrahydrobiopterin (BH4) , 10mg/kg/day will be given for three months. Then the patient will be given three additional months of open label BH4 at the same rate. | Drug | Control Arm, Treatment Arm |
Primary outcome
Blood Phe level decrease by 30%
Time frame: 9 months
Results and safety
The study was stopped early (reason given: The FDA has approved Kuvan (BH4) as a therapeutic agent for phenylketonuria). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2021.
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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.
Reuben Matalon, MD, PhD principal investigator
University of Texas
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing tetrahydrobiopterin (BH4) in people with Phenylketonuria, run by The University of Texas Medical Branch, Galveston 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 4 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: stopped early, as of the sponsor's last update on 21 Sep 2021. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 stopped early (reason given: The FDA has approved Kuvan (BH4) as a therapeutic agent for phenylketonuria). Results are not available in the source record.
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?
Blood Phe level decrease by 30% (time frame: 9 months). 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 21 Sep 2021; AzTrials last refreshed its copy on 8 Nov 2026.