Ignite Creation Date:
2024-05-05 @ 12:06 PM
Last Modification Date:
2024-10-26 @ 9:20 AM
Study NCT ID:
NCT00244218
Status:
TERMINATED
Last Update Posted:
2021-09-21
First Post:
2005-10-25
Brief Title:
Response to Phenylketonuria to Tetrahydrobiopterin BH4
Sponsor:
The University of Texas Medical Branch Galveston
Organization:
The University of Texas Medical Branch Galveston
Study Overview
Official Title:
Response to Phenylketonuria to Tetrahydrobiopterin BH4
Status:
TERMINATED
Status Verified Date:
2015-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
The FDA has approved Kuvan BH4 as a therapeutic agent for phenylketonuria
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to determine whether tetrahydrobiopterin BH4is effective in treating patients with PKU
Detailed Description:
PhenylketonuriaPKU is an autosomal recessive disorder caused by a defect in the enzyme phenylalanine hydroxylasePAH this incidence of PKU in the US is about 115000 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 mgkg 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 10mgkg 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 CBCs 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 umoll when less than 12 years of age or up to 900 umoll 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 10mgkgday 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
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 mgkg 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 10mgkg 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 CBCs 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 umoll when less than 12 years of age or up to 900 umoll 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 10mgkgday 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| FD-R-002600-01 | None | None | None |