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RecruitingNCT07069426Updated Sep 11, 2025

Muscle Response to Different Amounts of Dietary Protein During Leg Immobilization

An interventional study of 20 grams protein and 40 grams protein in Muscle Disuse and Muscle Disuse Atrophy, sponsored by United States Army Research Institute of Environmental Medicine. Recruiting at 1 site in United States. Open to participants aged 17 Years to 39 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-09-11.

Sponsored by United States Army Research Institute of Environmental Medicine · Not applicable, Interventional, and Basic science

Phase
Not applicable
Study type
Interventional
Enrollment
28
Allocation
Randomized
Ages
17 Years to 39 Years
Sex
All
01

Study summary

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)

Read the 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.

02

Conditions studied

  • Muscle Disuse
  • Muscle Disuse Atrophy

Keywords

  • muscle protein synthesis
  • muscle disuse
  • muscle disuse atrophy
  • immobilization
  • anabolic resistance
  • dose-response
03

Who can participate

Ages eligible
17 Years to 39 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

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

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.
04

Study design

Phase
Not applicable
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
28 participants (estimated)

Study arms

  • Active comparator
    Standard Protein Dose

    Participants will consume 20 g of whey protein after 5 days of muscle disuse

    Dietary Supplement: 20 grams protein

  • Active comparator
    High Protein Dose

    Participants will consume 40 g of whey protein after 5 days of muscle disuse

    Dietary Supplement: 40 grams protein

Interventions

  • Dietary supplement20 grams protein

    20 grams of whey protein provided as beverage

  • Dietary supplement40 grams protein

    40 grams of whey protein provided as beverage

05

What researchers measure

Primary outcomes

  1. Rates of postabsorptive and postprandial muscle protein synthesis assessed using 2H5-Phenylalanine stable isotope methodologies.

    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).

    Time frame: After 5 days of muscle disuse

06

Study locations

1 of 1 sites recruiting
  • US Army Research Institute of Environmental Medicine
    Natick, Massachusetts 01760, United States
    Recruiting
07

References and documents

Individual participant data

Plan to share: No — Individual participant data will not be shared.

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT07069426
Lead sponsor
United States Army Research Institute of Environmental Medicine
Responsible party
Sponsor
First posted
Jul 16, 2025
Start date
Sep 1, 2025
Primary completion
Sep 2026 (estimated)
Completion
Sep 2026 (estimated)
Last update
Sep 11, 2025

Study contacts

Emily E Howard, PhD
Contact
emily.e.howard14.civ@health.mli
508-206-2309

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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