Clinical Trial: Response to Phenylketonuria to Tetrahydrobiopterin (BH4)

Study Status: Suspended
Recruit Status: Unknown status
Study Type: Interventional

Official Title: Response to Phenylketonuria to Tetrahydrobiopterin (BH4)

Brief Summary: The purpose of this study is to determine whether tetrahydrobiopterin (BH4)is effective in treating patients with PKU.

Detailed Summary:

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 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 wil
Sponsor: FDA Office of Orphan Products Development

Current Primary Outcome: Blood Phe level decrease by 30% [ Time Frame: 9 months ]

Original Primary Outcome: Blood Phe level decrease by 30%

Current Secondary Outcome:

Original Secondary Outcome:

Information By: FDA Office of Orphan Products Development

Dates:
Date Received: October 25, 2005
Date Started: April 2005
Date Completion:
Last Updated: January 15, 2009
Last Verified: January 2009