Moderate Intensity Exercise and Phenylketonuria

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01904708
Recruitment Status : Terminated (Current design not able to measure the outcomes anticipated.)
First Posted : July 22, 2013
Last Update Posted : October 16, 2014
Information provided by (Responsible Party):
Melanie B Gillingham, Oregon Health and Science University

Brief Summary:

Phenylketonuria (PKU), an inherited genetic disorder, can cause irreversible brain damage, declined executive function, and autistic tendencies unless a phenylalanine (Phe) restricted diet is consistently maintained throughout life. Promoting anabolism, the uptake of free amino acids from the extracellular space, is a key component to maintaining plasma phenylalanine concentrations within treatment range among patients with PKU. Exercise promotes muscle protein synthesis and anabolism, but the effect on blood phenylalanine concentrations in patients with PKU has not been reported.

Our objective is to assess the impact of an acute bout of moderate intensity exercise on protein oxidation and plasma amino acid concentrations, as a potential adjunctive therapy for patients with PKU.

The investigators hypothesize that moderate intensity exercise decreases amino acid oxidation, increases muscle protein synthesis, and promotes tissue uptake of essential amino acids, thereby lowering plasma phenylalanine concentrations in patients with Phenylketonuria.

Condition or disease Intervention/treatment Phase
Phenylketonuria PKU Other: Acute Moderate Intensity Exercise Not Applicable

Detailed Description:

The indicator amino acid oxidation technique utilizes a carbon labeled isotope (L-[13C]) tracer that is ingested orally and is measured in expired breath. This method is based on the theory that if one essential amino acid is deficient, all other amino acids will be oxidized until a break-point is reached and at that time all amino acids will be incorporated into muscle protein synthesis. Using a randomized crossover design the investigators plan to investigate the effects of an acute bout of moderate intensity treadmill exercise versus sedentary activities on plasma amino acids in four subjects with PKU. The long-term goal of this novel research is to determine if exercise could be used as an adjunctive therapy to improve the management of plasma phenylalanine levels and promote a normal, healthy quality of life among patients with PKU.

Patient Recruitment: Four post-pubertal participants ranging from 14-17 years of age with classical phenylketonuria (PKU), treated at Oregon Health & Science University, will participate in this pilot study. Participants will be recruited during their routine clinic visit at Doernbecher Children's Hospital Metabolic clinic.

Study Design: This randomized crossover clinical trial will compare the effects of moderate intensity exercise and sedentary activities on amino acid oxidation and plasma amino acid pools using the indicator amino acid oxidation technique. Each participant will be studied on two separate occasions over a one-month period.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: The Effects of an Acute Bout of Moderate Intensity Exercise on Plasma Amino Acids in Subjects With Phenylketonuria
Study Start Date : May 2013
Actual Primary Completion Date : June 2014
Actual Study Completion Date : June 2014

Arm Intervention/treatment
No Intervention: Sedentary Visit
Subjects will do quiet, sedentary activities for 8 hours. Hourly blood draws and breath sampling will be collected. Bolus C13-Lysine will be given at hour 4.
Active Comparator: Exercise Visit
Subjects will do quiet, sedentary activities until hour 5. Blood and breath samples will be collected. At hour 4, subject will consume a bolus of C13-Lysine and immediately walk on a treadmill at a moderate intensity (exercise at 75% of max heart rate) for 45 minutes.
Other: Acute Moderate Intensity Exercise
Moderate intensity exercise by walking on a treadmill at 75% of max heart rate.

Primary Outcome Measures :
  1. Compare plasma phenylalanine concentration of final blood draw during exercise versus sedentary visits. [ Time Frame: up to 8 hours ]
    Compare the final blood sample for phenylalanine concentration from each arm of the study.

Secondary Outcome Measures :
  1. Breath Enrichment of C13-Lysine during sedentary and exercise [ Time Frame: Hours 1-8 of the study day from each arm. ]
    Compare the AUC total breath enrichment of C13-Lysine during the sedentary and exercise arms.

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Ages Eligible for Study:   14 Years to 17 Years   (Child)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • plasma phenylalanine concentration of >1200 micromols at diagnosis
  • treated by dietary phenylalanine restriction from early infancy
  • willing to participate in this study
  • stable BMI of 20-25 for the past 3 months
  • currently in average to good physical fitness condition
  • physically active 3-4 days per week

Exclusion Criteria:

  • previously or are currently taking approved or experimental pharmacologic treatments (i.e.: Biopterin (BH4), sapropterin dihydrochloride (Kuvan), Large Neutral Amino Acids (LNAA), pegylated phenylalanine ammonia lyase (PEG-PAL))
  • recent history of weight loss
  • endocrine disorder
  • pregnant
  • anemic
  • involved in any other study or research protocol
  • participation in a current strength training or performance training regimen

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01904708

United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239
Sponsors and Collaborators
Oregon Health and Science University
Principal Investigator: Melanie Gillingham, PhD, RD Oregon Health and Science University

Responsible Party: Melanie B Gillingham, Assistant Professor, Oregon Health and Science University Identifier: NCT01904708     History of Changes
Other Study ID Numbers: 9202
First Posted: July 22, 2013    Key Record Dates
Last Update Posted: October 16, 2014
Last Verified: October 2014

Keywords provided by Melanie B Gillingham, Oregon Health and Science University:
Muscle Protein Synthesis
Plasma Phenylalanine concentration

Additional relevant MeSH terms:
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