Phase 2 Study of Glycomacropeptide Versus Amino Acid Diet for Management of Phenylketonuria
Condition: Phenylketonuria
MeSH terms: Phenylketonurias
Study type: Interventional

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.
    

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.
    

Intervention name(s): GMP Diet/GMP Medical Foods; AA Diet/AA Medical Foods
Intervention type(s): Other; Other
Intervention description(s): 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.; 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.
Other intervention name(s): GMP Medical Foods; Glytactin trademark of Cambrooke Therapeutics,LLC; AA Medical Foods
Intervention MeSH terms: Coal Tar
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.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Diet therapy; Low phenylalanine diet; Attention; Executive function