Muscle Response to Different Amounts of Dietary Protein During Leg Immobilization

September 4, 2025 updated by: United States Army Research Institute of Environmental Medicine

The Effects of Varying Protein Intakes on Muscle Protein Synthesis During Injury-Mediated Muscle Disuse

Individuals who sustain musculoskeletal injuries (MSKI) can experience a rapid loss of muscle mass due to declines in muscle loading and activation that occur post-injury (i.e., disuse atrophy). Loss of muscle under these conditions is attributed to a persistent negative net muscle protein balance (muscle protein synthesis [MPS] < muscle protein breakdown) that results, in part, from declines in postprandial MPS (i.e., anabolic resistance). Nutritional interventions that enhance postprandial MPS may be used to overcome disuse-induced anabolic resistance and preserve muscle mass to accelerate recovery and improve recovery outcomes. While supplemental protein has been explored as a potential countermeasure to disuse-induce anabolic resistance, the observed efficacy of such interventions has been mixed. Equivocal findings across studies may be attributed, in part, to an insufficient understanding of what constitutes an effective protein-based intervention. Importantly, no study to date has determined an optimal protein dose for overcoming disuse-induce anabolic resistance, or if there is a threshold for maximally stimulating postprandial MPS under disuse conditions. Therefore, the objective of this work is to determine rates of MPS at rest and in response to standard (20 g) or high (40 g) doses of whey protein during knee immobilization (DISUSE) compared with standard activity (ACTIVE)

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

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Detailed Description

Healthy, recreationally active men and women will complete this randomized, double-blind, parallel study. Muscle disuse will be implemented for five days using a unilateral leg immobilization model with one leg assigned to immobilization (DISUSE) and the contralateral leg used as a control (ACTIVE). Immobilization will be implemented with a rigid knee brace fixed at ~60° of flexion and participants will ambulate using crutches. Diets will be standardized during the immobilization phase. Participants will complete a protein feeding study at the end of immobilization consisting of primed, continuous stable isotope infusions, serial blood draws, and muscle biopsies. MPS will be assessed in both the DISUSE and ACTIVE legs in response to standard (20 g) or high (40 g) doses of whey protein. Findings from this work will directly inform the development of targeted nutritional countermeasures for overcoming disuse-induced anabolic resistance and preserving muscle mass after MSKI to optimize physical performance recovery.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
28

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

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Study Contact

Study Contact

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Study Locations

  • United States
    • Massachusetts
      • Natick, Massachusetts, United States, 01760
        • Recruiting
        • US Army Research Institute of Environmental Medicine
        • Contact:
        • Principal Investigator:
          • Emily E Howard, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Men and women aged 18-39 years (17-39 years if military personnel)
  • Body mass index (BMI) between 18.5-32 kg/m2
  • 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), and dietary supplements (i.e., vitamin D, probiotics) 24 hours before and during immobilization and final testing day.
  • Willing to only consume caffeine products provided by study staff during the study.
  • Supervisor approval for federal civilian employees and non-SRV active-duty military personnel stationed at 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., IUD or oral contraceptives without placebo).

Exclusion Criteria:

  • 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.).
  • Taking medication that affects macronutrient utilization (i.e., statins, corticosteroids, weight loss medications such as Ozempic, etc.).
  • Significantly abnormal blood clotting as determined by USARIEM Office of Medical Oversight (OMSO) or home duty station medical support (HMS).
  • Allergy to lidocaine (or similar local anesthetic).
  • Present condition of alcoholism, anabolic steroid use, or other substance abuse issues as determined by OMSO or HMS.
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Standard Protein Dose
Participants will consume 20 g of whey protein after 5 days of muscle disuse
Dietary supplement: 20 grams protein
20 grams of whey protein provided as beverage
Active Comparator: High Protein Dose
Participants will consume 40 g of whey protein after 5 days of muscle disuse
Dietary supplement: 40 grams protein
40 grams of whey protein provided as beverage

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Rates of postabsorptive and postprandial muscle protein synthesis assessed using 2H5-Phenylalanine stable isotope methodologies.
Time Frame: After 5 days of muscle disuse
Postabsorptive and postprandial muscle protein synthesis in response to 20 or 40 g of whey protein determined using 2H5-Phenylalanine stable isotope methodologies and expressed as fractional synthetic rate (FSR).
After 5 days of muscle disuse

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
United States Army Research Institute of Environmental Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 21, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 7, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 16, 2025

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 11, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 4, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 25-04H
  • MO240092 (Other Grant/Funding Number: MOMRP)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data will not be shared.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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