Molecular Mechanisms Underlying Anabolic Resistance to Protein Intake During Muscle Disuse

NCT06228742 | Completed

• 1 other identifier: 24-02
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This study will characterize intramuscular molecular mechanisms underlying anabolic resistance to protein ingestion during muscle disuse. Adults (n=12) will be studied using a unilateral leg immobilization model in which one leg will be randomly assigned to immobilization and the contralateral, active leg used as a within-subjects control. Immobilization will be implemented for five days using a rigid knee brace, during which time participants will ambulate using crutches. Integrated ribonucleic acid (RNA) synthesis will be determined during immobilization in the immobilized and non-immobilized legs using ingested deuterium oxide, salivary and blood sampling, and muscle biopsies. Immediately after immobilization, muscle biopsies will be collected before and 90 mins after consuming 25 g of whey protein from the immobilized and non-immobilized legs to characterize the intramuscular molecular response to protein feeding. Serial blood samples will be collected during that time to characterize the circulating metabolic response to protein ingestion. Knowledge generated from this effort will inform the development of targeted interventions for mitigating anabolic resistance to protein ingestion that develops during periods of muscle disuse.

Conditions

Atrophy, Disuse; Muscle Atrophy; Muscular Disorders, Atrophic; Disuse Atrophy; Disuse Atrophy Muscle of Thigh

Outcome Measures

Primary Outcomes (2)

• Integrated ribonucleic acid (RNA) synthesis

  deuterium oxide coupled with muscle biopsies

  5 days

• Intramuscular protein signaling response to protein ingestion

  muscle biopsies to assess protein signaling response to consuming 25 g of whey protein

  90 minutes

Study Arms (2)

Immobilized Leg

EXPERIMENTAL

One leg of a young, healthy adult will be randomly assigned to undergo 5 days of immobilization using a rigid knee brace.

Other: Unilateral leg immobilization

Non-immobilized leg

EXPERIMENTAL

One leg of a young, healthy adult will remain active and not immobilized for 5 days.

Other: Contralateral active leg

Interventions

Unilateral leg immobilization OTHER

Participants will have one leg immobilized using a rigid knee brace. Participants will be expected to keep the knee brace on for 5 days and remain non-weight bearing on the immobilized leg. Participants will use crutches to remain non-weight bearing on the immobilized leg.

Also known as: DISUSE

Immobilized Leg

Contralateral active leg OTHER

One leg will remain non-immobilized and active during the study. Participants will use this leg to walk with crutches.

Also known as: ACTIVE

Non-immobilized leg

Eligibility Criteria

• Age: 18 Years - 39 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Men and women aged 18-39 years.
• Body mass index (BMI) between 18.5-30 kg/m2
• Healthy without evidence of chronic illness (e.g., diabetes, cardiovascular disease, Crohn's disease) or musculoskeletal injury as determined by the USARIEM Office of Medical Oversight (OMSO) or home duty station medical support.
• Routinely participate in aerobic and/or resistance exercise at least 2 days per week.
• Willing to refrain from alcohol, smoking, smokeless nicotine products (includes e-cigarettes, vaping, chewing tobacco), caffeine, and dietary supplements (i.e., vitamin D, probiotics) during the run-in diet, immobilization phase, and final testing day of the study.
• Supervisor approval for federal civilian employees and non-human research volunteer (HRV) active-duty military personnel stationed at Natick Soldier System Center (NSSC).
• Biological females must have normal menstrual cycles between 26-32 days in duration; 5 menstrual cycles within the past 6 months; or on continuous hormonal contraception (i.e., intrauteraine device (IUD) or oral contraceptives without placebo).

You may not qualify if:

• Musculoskeletal injuries that may interfere with the safe use of crutches.
• Personal or family history of thrombosis, or prior diagnosis of deep vein thrombosis (DVT) or pulmonary embolism (PE).
• Metabolic or cardiovascular abnormalities, gastrointestinal disorders, neuromuscular disorders, lower-limb amputation, or muscle/bone wasting disorders (e.g., diabetes, cardiovascular disease, Crohn's disease, etc.).
• Significantly abnormal blood clotting as determined by OMSO or home duty station medical support.
• Allergy to lidocaine (or similar local anesthetic)
• Present condition of alcoholism, anabolic steroid use, or other substance abuse issues as determined by OMSO or home duty station medical support.
• Blood donation within 8-wk of beginning the study.
• Pregnant, trying to become pregnant, and/or breastfeeding (results of urine pregnancy test and self-report for breastfeeding will be obtained before body composition testing).
• Unwilling or unable to consume study diets or foods provided due to personal preference and/or food allergies.
• Unwilling or unable to adhere to study physical restrictions (i.e., no structured physical activity or recreational activity beyond activities of daily living) 24 hours before and during immobilization, and the final testing day.
• Unwilling or unable to keep the knee brace on and walk with crutches during the immobilization phase.

Sponsors & Collaborators

• United States Army Research Institute of Environmental Medicine: lead

Study Sites (1)

US Army Research Institute of Environmental Medicine

Natick, Massachusetts, 01760, United States

Location

MeSH Terms

Conditions

Muscular Disorders, Atrophic; Muscular Atrophy

Interventions

Exercise

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Emily E Howard, PhD

  US Army Research Institute of Environmental Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Nutrition Physiologist

Model Details: Single leg immobilization model consisting of one leg randomly assigned to immobilization with a knee brace and the other leg remaining active and non-immobilized, for 5 days.

Study Record Dates

• First Submitted: January 18, 2024
• First Posted: January 29, 2024
• Study Start: February 20, 2024
• Primary Completion: October 1, 2024
• Study Completion: October 1, 2024
• Last Updated: December 2, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)