At a glance
ClinicalIndex Comparison RecordStandardized by ClinicalIndex from the ClinicalTrials.gov record · verify against the source.
The Effectiveness of High-Dose Synthetic BH4 (Saproterin Dihydrochloride or "Kuvan") in Amish PKU Patients
In Brief
A Phase 4 clinical trial evaluating saproterin dihydrochloride and Diet treatment for Phenylketonuria. Completed, enrolled 7 participants across 1 site.
Detailed Summary
The purpose of this study is to determine if Amish patients with PKU show responsiveness after a high dose, prolonged Saproterin trial. The population of interest has a high frequency of a specific splice site mutation, the 1066-11G\>A mutation. This splice site mutation activates a cryptic splice site resulting in an in frame insertion of 9 nucleotides preceding exon 11. This leads to protein conformational changes and abrogation of function. Previous studies of this genotype have indicated \<1% residual activity of the PAH enzyme and an insignificant responsiveness to Saproterin. However, in this specific study Phe levels were evaluated only over 24 hours after a single-dose BH4 challenge at the standard dose of 20mg/kg. Based on new clinical information, the investigators hypothesize that if given a prolonged trial of Saproterin at a higher dose, Amish patients with PKU, specifically those homozygous for the c.1066-11G\>A mutation, will have a significant reduction in Phe levels or an increase in Phe tolerance and/or improvement in executive functioning and quality of life.
Study Details
Timeline
Interventions
The drug will be given as described in the arm/group descriptions.
Patients will maintain a stable, Phe restricted diet (including formula) that is consistent with their diet at the time of enrollment. This will be monitored by food diaries kept for 3 days of each week.