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

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

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT04887727
Enrollment
22
Registered
2021-05-14
Start date
2019-02-25
Completion date
2019-08-31
Last updated
2021-05-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy Adult Males

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).

Interventions

DIETARY_SUPPLEMENTCrystalline amino acids to assess myofibrillar protein synthesis rates

Amino acid dose = 0.25g/kg bodyweight

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

Amino acid dose = 0.25g/kg bodyweight

Sponsors

University of Toronto
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Intervention model description

Three groups: Fast, Fed, Ex-Fed Two trials per group

Eligibility

Sex/Gender
MALE
Age
18 Years to 35 Years
Healthy volunteers
Yes

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.

Design outcomes

Primary

MeasureTime frameDescription
Myofibrillar protein synthesis rates5 hoursMyofibrillar protein synthesis rates assessed by oral and intravenous tracers during Fast, Fed, and Ex-Fed

Secondary

MeasureTime frameDescription
Whole-body protein turnover5 hoursWhole-body protein turnover assessed by oral and intravenous tracers during Fast, Fed, and Ex-Fed
Amino acid oxidation and net protein balance5 hoursAmino 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.
Muscle anabolic signalling2 and 5 hoursImmunoblotting for mTORC1/key downstream targets of mTORC1
Amino acid transporter expression2 and 5 hoursImmunoblotting for amino acid transporters LAT1/SNAT2

Countries

Canada

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 12, 2026