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Response to Phenylketonuria to Tetrahydrobiopterin (BH4)

Primary Purpose

Phenylketonuria

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
tetrahydrobiopterin (BH4)
Sponsored by
The University of Texas Medical Branch, Galveston
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Phenylketonuria focused on measuring phenylketonuria, hyperphenylalaninemia

Eligibility Criteria

10 Years - undefined (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: 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 Exclusion Criteria: 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

Sites / Locations

  • University of Texas Medical Branch

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Treatment Arm

Control Arm

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Blood Phe level decrease by 30%

Secondary Outcome Measures

Full Information

First Posted
October 25, 2005
Last Updated
September 20, 2021
Sponsor
The University of Texas Medical Branch, Galveston
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1. Study Identification

Unique Protocol Identification Number
NCT00244218
Brief Title
Response to Phenylketonuria to Tetrahydrobiopterin (BH4)
Official Title
Response to Phenylketonuria to Tetrahydrobiopterin (BH4)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2015
Overall Recruitment Status
Terminated
Why Stopped
The FDA has approved Kuvan (BH4) as a therapeutic agent for phenylketonuria
Study Start Date
April 2005 (undefined)
Primary Completion Date
March 2009 (Actual)
Study Completion Date
January 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The University of Texas Medical Branch, Galveston

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Phenylketonuria
Keywords
phenylketonuria, hyperphenylalaninemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
57 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment Arm
Arm Type
Experimental
Arm Description
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.
Arm Title
Control Arm
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
tetrahydrobiopterin (BH4)
Other Intervention Name(s)
BH4
Intervention Description
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.
Primary Outcome Measure Information:
Title
Blood Phe level decrease by 30%
Time Frame
9 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
10 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Reuben Matalon, MD, PhD
Organizational Affiliation
University of Texas
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Texas Medical Branch
City
Galveston
State/Province
Texas
ZIP/Postal Code
77555
Country
United States

12. IPD Sharing Statement

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Response to Phenylketonuria to Tetrahydrobiopterin (BH4)

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