Modified Breath Test to Determine Anabolic Sensitivity Across Physical Activity States

NCT ID: NCT06209424

Last Updated: 2024-01-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-15
• Study Completion Date: 2025-04-30

Brief Summary

Developing tools to detect when our bodies are more resistant towards protein synthesis is valuable for identification of when someone may be at risk of losing body or muscle mass such as with aging or certain diseases. The current study aims to refine our previous breath test method to be more effective at measuring changes in how the body processes protein in different situations, such as resting, reducing physical activity, and doing resistance exercise. We hypothesize that using a lower amount of dietary amino acids in our breath test will be effective at detecting lower amounts of amino acids used after exercise, and a greater amount with step reduction compared to normal activity levels

Detailed Description

Maintaining high-quality and abundant lean body mass (LBM) is crucial for growth, health, and performance across all ages, sexes, and activity levels. Body protein, including skeletal muscle, undergoes constant turnover, breaking down old and damaged proteins and using dietary amino acids (AA) to synthesize new proteins, especially after resistance exercise. Unused AA are oxidized for energy and excreted as carbon dioxide (CO2). Studying the proportion of AA used for protein synthesis versus energy production provides insights into acute growth of LBM after a meal in different physiological states (e.g., at rest or exercise). Stable isotope tracers, commonly administered intravenously, are used in protein metabolism research to examine the effects of nutrition and exercise on protein turnover. However, this method may not be feasible for vulnerable populations.

While exercise has been shown to enhance anabolic sensitivity (i.e., greater utilization of dietary AA for protein synthesis), step-reduction leads to fed-state anabolic resistance (I.e., reduced utilization of dietary AA for protein synthesis). Indeed, reduced habitual activity, whether mild or severe, leads to fed-state anabolic resistance, reducing the muscle protein synthesis (MPS) response to amino acids. For instance, one week of reduced daily steps (~1,192 steps/day) decreased MPS rates by approximately 27% in young males who habitually reach ~10,000 steps/day, i.e., a ~75% reduction from habitual.

Therefore, developing metabolic tools to detect anabolic resistance before muscle mass loss occurs would be valuable for both treatment and prevention of age-related muscle loss. Recently, our laboratory demonstrated the effectiveness of a non-invasive stable isotope "breath test" to detect increased anabolic sensitivity in males after resistance exercise. This study, in addition to ongoing metabolic trials in our lab, utilized a protein dose of 0.25g/kg which has been shown to maximize the rate of myofibrillar protein synthesis and to support whole-body protein synthesis. However, this dose may not adequately distinguish between more subtle changes in anabolic sensitivity. Further, a lower protein dose may reduce the duration for which breath samples would need to be collected, which would minimize participant burden and time commitment going forward.

Therefore, the present project will use previously established 'breath test' methodology but with a lower protein dose to assess the following objectives:

1. To investigate whether the 'optimized' non-invasive breath test can detect changes in anabolic sensitivity (i.e., leucine oxidation) across varying physiological states (I.e., rest, step-reduction, whole-body resistance exercise) after feeding, in young healthy adults.

2. To assess the reproducibility, and day-to-day variability of our breath test during habitual activity in both an at-home and a controlled laboratory setting

Conditions

Resistance Exercise; Physical Inactivity; Amino Acids; Dietary Protein

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

In-Person Phase

Habitual Activity + Resistance Exercise Metabolic Trials

Group Type: ACTIVE_COMPARATOR

Habitual Activity

Intervention Type: BEHAVIORAL

Participants will maintain habitual levels of physical activity (inclusive of structured physical activity).

Resistance Exercise

Intervention Type: BEHAVIORAL

Participants will undergo a 50-minute resistance exercise protocol, which includes multiple sets of different exercises using weights. Each set will consist of 10 repetitions at 75% of their 1 repetition maximum (1RM). The exercises include bench press superset with lat pulldowns, overhead press superset with seated cable rows, leg press, and leg extensions with 90s rest in between sets. Before the exercise protocol, there will be a standardized 10-minute warm-up that involves cycling, leg swings, arm circles, bodyweight squats, and bench push-ups

At-Home Phase

Habitual Activity + Step-Reduction Metabolic Trials

Group Type: ACTIVE_COMPARATOR

Habitual Activity

Intervention Type: BEHAVIORAL

Participants will maintain habitual levels of physical activity (inclusive of structured physical activity).

Step-Reduction

Intervention Type: BEHAVIORAL

Participants will be required to reduce their daily step-counts to \<2,000 steps/day. Further, they will be required to refrain from structured physical activity.

Interventions

Habitual Activity

Participants will maintain habitual levels of physical activity (inclusive of structured physical activity).

Intervention Type: BEHAVIORAL

Step-Reduction

Participants will be required to reduce their daily step-counts to \<2,000 steps/day. Further, they will be required to refrain from structured physical activity.

Intervention Type: BEHAVIORAL

Resistance Exercise

Participants will undergo a 50-minute resistance exercise protocol, which includes multiple sets of different exercises using weights. Each set will consist of 10 repetitions at 75% of their 1 repetition maximum (1RM). The exercises include bench press superset with lat pulldowns, overhead press superset with seated cable rows, leg press, and leg extensions with 90s rest in between sets. Before the exercise protocol, there will be a standardized 10-minute warm-up that involves cycling, leg swings, arm circles, bodyweight squats, and bench push-ups

Intervention Type: BEHAVIORAL

Other Intervention Names

Free-Living Activity; Reduced Physical Activity; Full-Body Resistance Exercise

Eligibility Criteria

Inclusion Criteria

• Healthy young (age: 18-35 years)
• BMI between normal to overweight (18.5-29.9 kg/m2)
• if oral contraceptive (OC) user, must be on monophasic OCs for at least 3 months prior to study
• if non-OC user, then must have regular menstrual cycles (length: 25-35 days) for at least 3 months prior to study and at least 6 months off of OCs

Exclusion Criteria

• Chronic disease diagnosis (cardiovascular, thyroid, diabetes)
• Current or recent remission of cancer
• Regular use of NSAID (except low-dose aspirin), anticoagulants
• Use of prescription drugs that would impact muscle protein synthesis (e.g., Statins, Lithium, ADHD medication, etc..)
• Insertion of intrauterine device (IUD) - exception: copper
• Smoking
• Use of illicit drugs (growth hormones, testosterone)

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

Sponsors

University of Toronto

OTHER

Sponsor Role: lead

Responsible Party

Daniel Moore

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ines Kortebi, MSc

Role: STUDY_DIRECTOR

University of Toronto

Hugo JW Fung, PhD (c)

Role: STUDY_CHAIR

University of Toronto

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

Site Status: RECRUITING

Countries

Canada

Central Contacts

Daniel R Moore, PhD

Role: CONTACT

dr.moore@utoronto.ca

4169464088

Hugo JW Fung, PhD (c)

Role: CONTACT

hugojernwai.fung@utoronto.ca

6472098764

Facility Contacts

Daniel R Moore, PhD

Role: primary

dr.moore@utoronto.ca

416464088

Hugo JW Fung, PhD (c)

Role: backup

hugojernwai.fung@utoronto.ca

6472098764

Other Identifiers

00044918

Identifier Type: -

Identifier Source: org_study_id