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Completed

NCT Number: NCT04887727

Development of Oral Amino Acid Tracers to Study Protein Turnover in Humans

Previous studies have used a combination of oral L-[1-13C]leucine and intravenous labeled L-[5,5,5-2H3]leucine to assess the acute postprandial changes in whole-body protein turnover (12, 19). Intravenous and dietary-labeled amino acid tracers have also been used in tandem to assess rates of myofibrillar protein synthesis in response to bolus protein ingestion and resistance exercise (46). By validating whole-body net balance to myofibrillar protein synthesis, our proposed multi-tracer approach will develop minimally invasive models to study protein turnover in a variety of populations in which traditional infusions and/or repeated blood samples are not possible (i.e. pediatric, free-living populations).

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Key information

Conditions

Age range

18 year–35 year

Sex eligibility

Male

Study type

Interventional

Phase

Not applicable

Primary location

Goldring Centre for High Performance Sport at the University of Toronto

Toronto, Ontario, M5S2C9, Canada

About this study

The primary objective of the proposed study is to validate the use of a novel oral tracer model to accurately and reliably measure myofibrillar protein synthesis. It is hypothesized that oral L-[1-13C]leucine and L-[ring-2H5]phenylalanine, ingested as a bolus to mimic an intravenous 'pulse dose' administration (51, 65), will reveal similar rates of myofibrillar protein synthesis when compared to traditional intravenous L-[5,5,5-2H3]leucine infusion. Moreover, it is hypothesized that both methods will reveal the expected graded changes in myofibrillar protein synthesis in response to feeding and resistance exercise (i.e. fasted<feeding<exercise & feeding).

The secondary objective of the proposed study is to develop and validate non-invasive models to measure whole-body amino acid oxidation and net balance in response to feeding and resistance exercise. It is hypothesized that whole-body net balance, as determined by a novel oral tracer model (i.e. L-[1-13C]leucine) , will align with traditional intravenous tracer methodology (i.e. L-[5,5,5-2H3]leucine) and reveal the expected physiological changes in whole-body protein turnover in response to feeding and resistance exercise (i.e. fasted<feeding<exercise & feeding).

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Male
  • Currently performing structured physical activity 2-5 days per week

Exclusion criteria

  • Unable to safely perform exercise as per PARQ+ guidelines
  • Currently using tobacco products
  • Currently using or have history of anabolic steroid use
  • Diagnosed with medical condition including type 2 diabetes, cancer, heart disease
  • Unable to abstain from supplement use (HMB, branched chain amino acids, phosphatidic acid) for at least three weeks prior to trial
  • currently using medications known to affect protein metabolism e.g. corticosteroids, NSAID, prescription-strength acne medication
  • allergic to local anesthetics
  • female: Hormonal fluctuations associated with the menstrual cycle have been reported to alter protein metabolism during exercise and may influence indices of the post-exercise myofibrillar protein synthetic response. Accordingly, the study will include males to ensure a stable hormonal environment and to increase the homogeneity of the physiological response.

Treatment and study plan

Crystalline amino acids to assess myofibrillar protein synthesis rates

Dietary Supplement

Amino acid dose = 0.25g/kg bodyweight

Crystalline amino acids to assess whole-body protein turnover, amino acid oxidation, and net protein balance

Dietary Supplement

Amino acid dose = 0.25g/kg bodyweight

Primary outcomes

  1. Myofibrillar protein synthesis rates

    Time frame: 5 hours

    Myofibrillar protein synthesis rates assessed by oral and intravenous tracers during Fast, Fed, and Ex-Fed

Secondary outcomes

  1. Whole-body protein turnover

    Time frame: 5 hours

    Whole-body protein turnover assessed by oral and intravenous tracers during Fast, Fed, and Ex-Fed

  2. Amino acid oxidation and net protein balance

    Time frame: 5 hours

    Amino acid oxidation and net protein balance assessed by oral tracers during Fast, Fed, and Ex-Fed. Net protein balance is derived from the difference between amino acid intake (known) and total amino acid oxidation over the 5h measurement period.

  3. Muscle anabolic signalling

    Time frame: 2 and 5 hours

    Immunoblotting for mTORC1/key downstream targets of mTORC1

  4. Amino acid transporter expression

    Time frame: 2 and 5 hours

    Immunoblotting for amino acid transporters LAT1/SNAT2

Sponsors and collaborators

Lead sponsor

University of Toronto

Other

Registry information

Important dates

Study start
2019
Primary completion
2019
Study completion
2019
First posted
May 14, 2021
Registry last updated
May 14, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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