Dynamic Proteomics and Integrated Rates of Muscle Protein Synthesis During an Acute Period of Loading and Unloading (HYPAT)

Dynamic Proteomics and Integrated Rates of Muscle Protein Synthesis During an Acute Period of Hypertrophy and Atrophy (HYPAT) in Young, Healthy Men

Skeletal muscle plays several different roles in the promotion and maintenance of health and well-being. The loss of muscle mass that occurs with aging, chronic muscle wasting diseases, and physical inactivity puts people at an increased risk of frailty and becoming insulin resistant, and therefore imposes a significant burden on health care spending. Resistance exercise participation has proven particularly effective for increasing muscle mass and strength. This effectiveness can be used by health care practitioners in a rehabilitation setting to promote the recovery of individuals who have undergone involuntary periods of muscular unloading (i.e. limb immobilization caused by a sports injury or reconstructive surgery). However, there is large variability in the amount of muscle mass and strength that people gain following participation in resistance exercise. Some individuals fail to increase the size of their muscle (low responders) whereas others show vary large increases in muscle size (high responders) in response to the same resistance training program. People also show differences in the amount of muscle tissue they lose when they have a limb immobilized. To circumvent variability across individuals, the investigators utilized a within-person paired Hypertrophy and Atrophy ('HYPAT') strategy that reduced response heterogeneity by ~40% (Available at: https://ssrn.com/abstract=3445673). Specifically, one leg performed resistance training for 10 weeks to induce hypertrophy, whereas the other leg underwent single-leg immobilization for 2 weeks to induce atrophy. The primary goal of the study will be to gain insight into the molecular responses to an acute period of single-leg immobilization and resistance exercise (8 days). The investigators will use an integrated systems biology approach to monitor the individual rates of over one hundred different muscle proteins.

Study Overview

• Status: Active, not recruiting
• Conditions: Hypertrophy; Exercise; Proteomics; Atrophy, Disuse
• Intervention / Treatment: Other: Unilateral Resistance Exercise Training; Procedure: Knee bracing

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8S 4K1
      • Exercise Metabolism Research Laboratory, McMaster Univeristy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy males, between the ages of 18 and 30 y
• Body Mass Index between 18.5 and 30.0 kg/m2
• Able and willing to provide informed consent

Exclusion Criteria:

• A history of neuromuscular disorders or muscle/bone wasting diseases.
• Any acute or chronic illness, cardiac, pulmonary, liver, or kidney abnormalities, uncontrolled hypertension, insulin-dependent or insulin-independent diabetes, or the presence of any other metabolic disease - all of which will be determined via a medical history screening questionnaire.
• The use of any medications known to affect protein metabolism (glucocorticoids, non-steroidal anti-inflammatory medication, or prescription strength acne medication, etc.).
• A (family) history of thrombosis.
• The use of anticoagulant medications.
• Consumption of tobacco-containing products.
• Excessive alcohol consumption (>21 units/wk).
• History of bleeding diathesis, platelet or coagulation disorders, or anti-platelet/anticoagulation therapy.
• Exercise participation >2 days/wk (structured resistance and/or aerobic-type exercise)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Unilateral Resistance Exercise; One leg will undergo 4 sessions of unilateral resistance exercise, over the course of 8 days. Specifically, participants will be asked to perform leg press and leg extension.	Other: Unilateral Resistance Exercise Training; Participants will perform resistance training on 4 occasions throughout an 8 day time period.
Experimental: Unilateral Immobilization; One leg will undergo 14 days of single-leg immobilization, by means of a removable knee brace.	Procedure: Knee bracing; Participants will have one leg immobilized, by means of a removable Don Joy Knee Brace. Participants will be expected to keep the knee brace on for 14 days, completely prevent weight bearing on the immobilized leg, and use crutches.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Dynamic Proteomics	The investigators will use deuterated water and skeletal muscle biopsies, paired with sensitive Gas Chromatography-Mass Spectrometry techniques to calculate the individual synthesis rate of over one hundred different skeletal muscle proteins.	Baseline, Day 5, Day 9 and Day 14 (Post)
Change in Integrated Rates of Muscle Protein Synthesis	The investigators will use deuterated water and skeletal muscle biopsies to calculate the cumulative synthesis of skeletal muscle proteins.	Baseline, Day 5, Day 9 and Day 14 (Post)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Lean Mass Using Dual X-Ray Absorptiometry	The change in lean mass (kg) will be assessed throughout the intervention using dual X-Ray absorptiometry at baseline, Day 4, and Day 8 (Post) of the intervention	Baseline, Day 5 and Day 14 (Post)
Change in Muscle Strength using an Isokinetic Dynamometer	Muscle strength will be analyzed throughout the intervention using an isokinetic dynamometer. Isometric muscle torque (i.e., strength [N*m]) of the knee extensor will be measured.	Baseline, Day 5 and Day 14 (Post)
Change in Muscle Cross-Sectional Area using Ultrasonography	The investigators will measure changes in vastus lateralis muscle cross sectional area (cm^2) throughout the intervention using ultrasonography.	Baseline, Day 5 and Day 14 (Post)

Collaborators and Investigators

• Sponsor: McMaster University

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2021
• Primary Completion (Actual): September 1, 2022
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: June 29, 2020
• First Submitted That Met QC Criteria: August 12, 2020
• First Posted (Actual): August 17, 2020

Study Record Updates

• Last Update Posted (Actual): October 2, 2024
• Last Update Submitted That Met QC Criteria: October 1, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Pathological Conditions, Anatomical; Hypertrophy; Atrophy; Muscular Disorders, Atrophic
• Other Study ID Numbers: 10624

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All participants will be assigned a unique subject ID, and therefore, other researchers involved with analyses will not have access to identifying participant information.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No