Phase 2 Study of Glycomacropeptide Versus Amino Acid Diet for Management of Phenylketonuria (PKU)

University of Wisconsin (UW)

Status: Completed

Conditions: Phenylketonuria

Treatments: Other: GMP Diet/GMP Medical Foods; Other: AA Diet/AA Medical Foods

Study type: Interventional

Funder types: Other

Identifiers

NCT01428258

H-2010-0165

1R01FD003711-01A1

Details and patient eligibility

About

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.

Full 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.

Enrollment: 32 patients

Sex: All

Ages: 12 to 45 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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32 participants in 2 patient groups

GMP Diet/GMP Medical Foods

Experimental group

Description:

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.

Treatment:

Other: AA Diet/AA Medical Foods

AA Diet/AA Medical Foods

Active Comparator group

Description:

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.

Treatment:

Other: GMP Diet/GMP Medical Foods