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

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
Children's Hospital Boston
Information provided by (Responsible Party):
University of Wisconsin, Madison
ClinicalTrials.gov Identifier:
NCT01428258
First received: August 31, 2011
Last updated: May 5, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Phenylketonuria
Dietary Supplement: Amino Acid (AA) Diet Given First
Dietary Supplement: Glycomacropeptide (GMP) diet given first
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 2 Study of Glycomacropeptide vs. Amino Acid Diet for the Management of PKU

Resource links provided by NLM:


Further study details as provided by University of Wisconsin, Madison:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    Plasma will be collected at each base week and after 3 weeks on each of the dietary treatments, glycomacropeptide and amino acid, following an overnight fast. Plasma phenylalanine concentration (along with the complete profile of free amino acids) will be determined with an amino acid analyzer in the Wisconsin State Lab of Hygiene. Statistical analysis to determine the significance of the change in plasma phe concentration when comparing the 2 diets will consist of a paired t test, pairing on subject.


Secondary Outcome Measures:
  • dietary compliance [ Time Frame: 3 week dietary treatment ] [ Designated as safety issue: No ]
    Compliance with the glycomacropeptide and amino acid dietary treatments will be assessed by daily protein logs completed throughout the 3 week period and compared with a two-tailed, paired t test.

  • cognitive function assessed by neuropsychological tests [ Time Frame: 3 weeks on each dietary treatment ] [ Designated as safety issue: No ]
    Each subject will be given neuropsychological tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) and the Delis Kaplan Executive Function System (D-KEFS) to assess specific components of attention and executive function at the end of the glycomacropeptide and amino acid dietary treatments.

  • measures of bone status [ Time Frame: 3 weeks on each dietary treatment ] [ Designated as safety issue: No ]
    The concentrations of vitamin D (25-OH and 1,25-diOH), bone specific alkaline phosphatase and N-telopeptide cross-links of Type I collagen will be measured in serum at each base week and after 3 weeks on the amino acid and glycomacropeptide dietary treatments.

  • 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 ] [ Designated as safety issue: No ]
    Subjects will spot their blood on filter paper and plasma will be obtained after venipuncture at each base week and after 3 weeks on each dietary treatment to compare phenylalanine concentrations from samples obtained at the same time but analyzed by different methods in the Wisconsin State Lab of Hygiene.

  • Bone mineral density determined by dual-energy X-ray absorptiometry (DXA) scan [ Time Frame: once during first 3 week dietary treatment ] [ Designated as safety issue: No ]
    Subjects will have a single DXA test to assess bone mineral density of the lumbar spine and total body during the first dietary treatment that they are randomly assigned to start with.


Estimated Enrollment: 30
Study Start Date: September 2011
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GMP Diet-AA Diet
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.
Dietary Supplement: Glycomacropeptide (GMP) diet given first
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.
Other Names:
  • GMP Medical Foods
  • Glytactin, trademark of Cambrooke Foods
Experimental: AA Diet - GMP Diet
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.
Dietary Supplement: Amino Acid (AA) Diet Given First
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.
Other Names:
  • GMP Medical Foods
  • Glytactin trademark of Cambrooke Foods

Detailed 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.

  Eligibility

Ages Eligible for Study:   12 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01428258

Locations
United States, Massachusetts
Children's Hospital of Boston
Boston, Massachusetts, United States, 02115
United States, Wisconsin
University of Wisconsin-Madison
Madison, Wisconsin, United States, 53706
Sponsors and Collaborators
University of Wisconsin, Madison
Children's Hospital Boston
Investigators
Study Director: Denise M Ney, PhD, RD Professor of Nutritional Sciences, University of Wisconsin-Madison
  More Information

Additional Information:
Publications:
Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT01428258     History of Changes
Other Study ID Numbers: H-2010-0165, 1R01FD003711-01A1
Study First Received: August 31, 2011
Last Updated: May 5, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Wisconsin, Madison:
Diet therapy
Low phenylalanine diet
Attention
Executive function

Additional relevant MeSH terms:
Phenylketonurias
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Amino Acid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Caseins
Chelating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014