Overview

This trial has been completed.

Condition phenylketonuria
Treatments gmp diet/gmp medical foods, aa diet/aa medical foods
Sponsor University of Wisconsin, Madison
Collaborator Boston Children’s Hospital
Start date September 2011
End date November 2015
Trial size 32 participants
Trial identifier NCT01428258, 1R01FD003711-01A1, H-2010-0165

Summary

For individuals with Phenylketonuria (PKU), the investigators hypothesize that glycomacropeptide will provide an acceptable form of low-phenylalanine dietary protein that will improve dietary compliance, blood phenylalanine levels, cognitive function, and ultimately quality of life compared with the usual amino acid based diet. The study is funded by the Food and Drug Administration (FDA) Office of Orphan Products Development Grants Program, R01 FD003711.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Intervention model crossover assignment
Intervention model description the study is a randomized, two-arm, crossover trial comparing the gmp diet and the aa diet in 30 subjects with pku > 12 years of age. subjects were randomized to start with either the gmp diet or the aa diet which they followed for 3-wk at home, followed by a 3-wk washout period when they resumed their usual aa diet, and then 3-wk of either the gmp diet or the aa diet whichever they did not consume first. each subject served as their own control; there was no control group. we studied medical foods - either aa or gmp medical foods which are not drugs. the fda did not require that we have an ind.
Primary purpose treatment
Masking no masking
Arm
(Experimental)
The experimental intervention is the GMP diet followed at home for 3-wk. In this randomized crossover study, half of subjects (n=15) were randomized to receive the GMP diet as the first arm, and half of the subjects (n=15) were randomized to receive the GMP diet as the second arm.
aa diet/aa medical foods AA Medical Foods
The intervention consists of a low-Phe diet in combination with commercial AA medical foods as consumed in each subject's usual diet. A total of 15 different commercial AA medical foods were consumed by subjects in the study. The diet is formulated to provide each subject with their typical daily intake of protein equivalents from AA medical foods. The AA dietary treatment period consists of all subjects following the AA diet for 3-wks at home. The AA Diet comparator intervention is administered in differing orders, GMP Diet/AA Diet or AA diet/GMP Diet.
(Active Comparator)
The experimental intervention is the AA diet followed at home for 3-wk. In this randomized crossover study, half of subjects (n=15) were randomized to receive the AA diet as the first arm, and half of the subjects (n=15) were randomized to receive the AA diet as the second arm.
gmp diet/gmp medical foods GMP Medical Foods
The intervention consists of a low-phenylalanine (Phe) diet in combination with medical foods made with the peptide GMP supplemented with limiting indispensable amino acids, as provided by Cambrooke Therapeutics, LLC. The diet is formulated to replace the protein equivalents provided by AA medical foods with GMP medical foods, keeping other dietary components constant. The GMP dietary treatment period consists of all subjects following the GMP diet for 3-wks at home. The GMP diet intervention is administered in differing orders, GMP Diet/AA Diet or AA diet/GMP Diet.

Primary Outcomes

Measure
Change in the Plasma Phenylalanine Concentration of PKU Subjects Fed the Glycomacropeptide Diet Compared With the Change When Fed the Amino Acid Diet
time frame: baseline to day 22 on each diet

Secondary Outcomes

Measure
Dietary Compliance
time frame: 3 week dietary treatment
Executive Function Assessed by BRIEF
time frame: day 22 of each dietary treatment
Vitamin D (25-OH) Plasma Concentration at Day 22
time frame: day 22 of each dietary treatment
Comparison of Phe Concentrations in Plasma With Concentrations in Dried Blood Spots
time frame: 4 times total, 2 per treatment
Bone-specific Alkaline Phosphatase (BSAP) Plasma Concentration at Day 22
time frame: day 22 of each dietary treatment
N-terminal Telopeptide (NTX) Plasma Concentration at Day 22
time frame: day 22 of each dietary treatment

Eligibility Criteria

All participants from 12 years up to 45 years old.

Inclusion Criteria: - Identified PKU by newborn screening; started diet treatment before 1 mo age - Diagnosis of classical or variant PKU with documented phenylalanine level of greater than 600 umol/L at 7-10d of age - Follows or willing to follow PKU diet and consume amino acid medical formula providing more than 50% of protein needs - Acceptance of glycomacropeptide foods determined prior to enrollment Exclusion Criteria: - Females who are pregnant or planning pregnancy - Individuals with mental deficits due to untreated or poorly controlled PKU - Individuals with any health condition deemed to interfere with participation

Additional Information

Official title Phase 2 Study of Glycomacropeptide vs. Amino Acid Diet for the Management of PKU
Description Individuals with phenylketonuria (PKU) lack the enzyme phenylalanine hydroxylase that is needed to metabolize the essential amino acid phenylalanine (phe). When eating a normal diet they show an elevated level of phe in blood that is toxic to the brain. In order to prevent brain damage and cognitive impairment, individuals with PKU must follow a lifelong, low-phe diet that is restricted in natural foods and requires ingestion of a phe-free amino acid (AA) formula. Most adolescents and adults with PKU find the AA formula unpalatable and go off the diet resulting in elevated blood phe levels and neuropsychological deterioration. Glycomacropeptide (GMP), an intact protein produced during cheese making, is uniquely suited to a low-phe diet because it is the only known dietary protein that contains minimal phe. Foods and beverages made with GMP are a palatable alternative to AA formula. The long term goal is to assess the safety, efficacy and acceptability of GMP for the nutritional management of PKU. The specific aim is to conduct a randomized, two-stage, 11-wk, crossover trial comparing the GMP diet with the AA diet in 30 subjects with PKU ≥12 years of age treated since birth with a low-phe AA diet. The sites are: University of Wisconsin-Madison, Waisman Center (primary) and Harvard University, Children's Hospital Boston. Subjects will be recruited and randomized to begin the first 3-wk of the study with either a low-phe diet in which the majority of dietary protein is provided by GMP or AA medical foods and then, after a 3-wk washout with intake of their usual diet, begin the second diet for 3-wk. Dietary education will be provided in a 1-wk base period preceding initiation of each diet.
Trial information was received from ClinicalTrials.gov and was last updated in February 2017.
Information provided to ClinicalTrials.gov by University of Wisconsin, Madison.