Moderate Intensity Exercise and Phenylketonuria

This study has been terminated.
(Current design not able to measure the outcomes anticipated.)
Sponsor:
Information provided by (Responsible Party):
Melanie B Gillingham, Oregon Health and Science University
ClinicalTrials.gov Identifier:
NCT01904708
First received: May 31, 2013
Last updated: October 15, 2014
Last verified: October 2014
  Purpose

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 Intervention
Phenylketonuria
PKU
Other: Acute Moderate Intensity Exercise

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Oregon Health and Science University:

Primary Outcome Measures:
  • Compare plasma phenylalanine concentration of final blood draw during exercise versus sedentary visits. [ Time Frame: up to 8 hours ] [ Designated as safety issue: No ]
    Compare the final blood sample for phenylalanine concentration from each arm of the study.


Secondary Outcome Measures:
  • Breath Enrichment of C13-Lysine during sedentary and exercise [ Time Frame: Hours 1-8 of the study day from each arm. ] [ Designated as safety issue: No ]
    Compare the AUC total breath enrichment of C13-Lysine during the sedentary and exercise arms.


Enrollment: 2
Study Start Date: May 2013
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   14 Years to 17 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01904708

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

No publications provided

Responsible Party: Melanie B Gillingham, Assistant Professor, Oregon Health and Science University
ClinicalTrials.gov Identifier: NCT01904708     History of Changes
Other Study ID Numbers: 9202
Study First Received: May 31, 2013
Last Updated: October 15, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Oregon Health and Science University:
Phenylketonuria
PKU
Exercise
Muscle Protein Synthesis
Plasma Phenylalanine concentration

Additional relevant MeSH terms:
Phenylketonurias
Amino Acid Metabolism, Inborn Errors
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Central Nervous System Diseases
Genetic Diseases, Inborn
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases

ClinicalTrials.gov processed this record on October 23, 2014