Clinical trial NCT04887727: Development of Oral Amino Acid Tracers to Study Protein Turnover in Humans
Official title: Development of Oral Amino Acid Tracers to Study Protein Turnover in Humans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy Adult Males
Lead sponsor: University of Toronto
Sponsor class: OTHER
First posted: 2021-05-14
Enrollment: 22
Sex: MALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Three groups: Fast, Fed, Ex-Fed Two trials per group
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Myofibrillar protein synthesis rates
timeFrame: 5 hours
Secondary outcomes:
measure: Whole-body protein turnover
timeFrame: 5 hours
measure: Amino acid oxidation and net protein balance
timeFrame: 5 hours
measure: Muscle anabolic signalling
timeFrame: 2 and 5 hours
measure: Amino acid transporter expression
timeFrame: 2 and 5 hours
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Goldring Centre for High Performance Sport at the University of Toronto
state: Ontario
Study officials:
affiliation: University of Toronto
name: Daniel R Moore, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.