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

NCT ID: NCT04887727

Last Updated: 2021-05-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-25
• Study Completion Date: 2019-08-31

Brief Summary

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).

Detailed Description

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).

Conditions

Healthy Adult Males

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Healthy, recreationally-active adult males - Muscle Trial

Subjects receive 0.25g/kg crystalline amino acids modelled after egg protein, enriched with L-\[1-13C\]leucine and L-ring-\[2H5\]phenylalanine with a primed-constant infusion of L-\[555-2H3\]leucine to assess myofibrillar protein synthesis rates

Group Type: EXPERIMENTAL

Crystalline amino acids to assess myofibrillar protein synthesis rates

Intervention Type: DIETARY_SUPPLEMENT

Amino acid dose = 0.25g/kg bodyweight

Healthy, recreationally-active adult males - Whole Body Trial

Subjects receive 0.25g/kg crystalline amino acids modelled after egg protein, enriched with L-\[1-13C\]leucine with a primed-constant infusion of L-\[555-2H3\]leucine to whole-body protein turnover, amino acid oxidation, and net protein balance

Group Type: EXPERIMENTAL

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

Intervention Type: DIETARY_SUPPLEMENT

Amino acid dose = 0.25g/kg bodyweight

Interventions

Crystalline amino acids to assess myofibrillar protein synthesis rates

Amino acid dose = 0.25g/kg bodyweight

Intervention Type: DIETARY_SUPPLEMENT

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

Amino acid dose = 0.25g/kg bodyweight

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

University of Toronto

OTHER

Sponsor Role: lead

Responsible Party

Daniel Moore

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Daniel R Moore, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Toronto

Locations

Goldring Centre for High Performance Sport at the University of Toronto

Toronto, Ontario, Canada

Countries

Canada

References

Mazzulla M, Hodson N, West DWD, Kumbhare DA, Moore DR. A non-invasive 13CO2 breath test detects differences in anabolic sensitivity with feeding and heavy resistance exercise in healthy young males: a randomized control trial. Appl Physiol Nutr Metab. 2022 Aug 1;47(8):860-870. doi: 10.1139/apnm-2021-0808. Epub 2022 May 24.

Reference Type: DERIVED

PMID: 35609328 (View on PubMed)

Other Identifiers

Connaught

Identifier Type: -

Identifier Source: org_study_id