Overview

This trial is active, not recruiting.

Condition phenylketonuria
Treatments amino acid (aa) diet given first, glycomacropeptide (gmp) diet given first
Phase phase 2
Sponsor University of Wisconsin, Madison
Collaborator Children's Hospital Boston
Start date September 2011
End date April 2016
Trial size 35 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
Endpoint classification safety/efficacy study
Intervention model crossover assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
In this randomized crossover study, half of subjects will be assigned to an arm that consists of the the GMP diet followed by the AA diet referred to as the Glycomacropeptide (GMP) diet given first intervention.
glycomacropeptide (gmp) diet given first GMP Medical Foods
The intervention compares a new low-phenylalanine (phe) dietary therapy for PKU, a diet containing foods and beverages made from GMP using Glytactin provided by Cambrooke Foods LLC, with the usual amino acid (AA) low-phe dietary therapy. PKU subjects in the GMP Diet-AA Diet Arm will follow the GMP diet that will replace all of the dietary protein equivalents provided by AA formula with foods and beverages made from GMP for 3 weeks followed by a 3 wk wash out period. They will then follow the usual AA diet for 3 weeks. Each dietary treatment period will maintain constant intake of total protein and phe and last for 3 weeks in subjects living at home.
(Experimental)
In this randomized crossover study, half of subjects will be assigned to an arm that consists of the AA diet followed by the GMP diet referred to as the Amino Acid (AA) Diet given first intervention.
amino acid (aa) diet given first GMP Medical Foods
The intervention compares the usual amino acid (AA) low-phenylalanine (phe) dietary therapy with a new dietary therapy for PKU, a low-phe diet containing foods and beverages made from glycomacropeptide (GMP). PKU subjects in the AA Diet-GMP Diet Arm will follow their usual AA diet for 3 weeks followed by a 3 wk wash out period. They will then replace all of the protein equivalents provided in their diet by AA formula with foods and beverages made from GMP using Glytactin as provided by Cambrooke Foods, LLC. Each dietary treatment period will maintain constant intake of total protein and phe and last for 3 weeks in subjects living at home.

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: 3 week on each diet

Secondary Outcomes

Measure
dietary compliance
time frame: 3 week dietary treatment
cognitive function assessed by neuropsychological tests
time frame: 3 weeks on each dietary treatment
measures of bone status
time frame: 3 weeks on each dietary treatment
comparison of phenylalanine concentrations in plasma analyzed with ion exchange chromatography with phenylalanine concentrations collected simultaneously by patients spotting their blood on filter paper and analyzed by tandem mass spectroscopy
time frame: 3 weeks on each dietary treatment
Bone mineral density determined by dual-energy X-ray absorptiometry (DXA) scan
time frame: once during first 3 week dietary treatment

Eligibility Criteria

Male or female 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 September 2015.
Information provided to ClinicalTrials.gov by University of Wisconsin, Madison.