Atrophy, DisuseNCT06228742
Molecular Mechanisms Underlying Anabolic Resistance to Protein Intake During Muscle Disuse
A study testing Unilateral leg immobilization and Contralateral active leg in people with Atrophy, Disuse and Muscle Atrophy, run by United States Army Research Institute of Environmental Medicine at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 39 yearsHealthy volunteers can take part
- Conditions the study is for
- Atrophy, Disuse, Muscle Atrophy, Muscular Disorders, Atrophic
- What is being tested?
- Unilateral leg immobilization and Contralateral active leg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Feb 2024to 1 Oct 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 39 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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).
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
US Army Research Institute of Environmental Medicine
Natick, Massachusetts, 01760
About this study
Official title: Molecular Regulation of Skeletal Muscle Anabolic Resistance to Dietary Protein in Response to Injury-mediated Muscle Disuse
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.
Read the detailed description
Warfighters that sustain musculoskeletal injuries often experience decreased muscle loading and activation post-injury (i.e., muscle disuse) that results in a rapid loss of muscle mass and function. Loss of muscle under these conditions is attributed to a persistent negative net muscle protein balance (muscle protein synthesis [MPS] < muscle protein breakdown [MPB]) that results, in part, from a blunting of MPS in the postprandial state. Nutritional interventions that optimize postprandial MPS have been suggested as countermeasures for this "anabolic resistance" that develops during disuse to preserve muscle mass and accelerate return to duty. However, a poor understanding of mechanisms underlying anabolic resistance during disuse has made it difficult to determine an optimal nutritional intervention. The current study will address this knowledge gap directly by characterizing intramuscular molecular mechanisms underlying anabolic resistance to protein ingestion during muscle disuse. Healthy, recreationally active men and women (n=12) will be studied using a within-subjects, unilateral design. After completing baseline measures of height, weight, and body composition, participants will begin a 3-day run-in phase where they will receive diet instructions (no food provided). Muscle disuse will then be implemented for 5 days using a unilateral leg immobilization model with one leg randomly assigned to immobilization and the contralateral, active leg used as a within-subjects control. Immobilization will be implemented using a rigid knee brace, and participants will ambulate using crutches. Diets will be standardized during the immobilization phase (1.0 g protein/kg/d, 30% of energy intake from fat, and the remaining calories from carbohydrate). 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
- Being tested
- Unilateral leg immobilization, Contralateral active leg
- Medical subject headings
- Muscular Disorders, Atrophic, Muscular Atrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Unilateral leg immobilizationOther
Also called DISUSE
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.
Contralateral active legOther
Also called ACTIVE
One leg will remain non-immobilized and active during the study. Participants will use this leg to walk with crutches.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Unilateral leg immobilization |
| Non-immobilized leg | Experimental | One leg of a young, healthy adult will remain active and not immobilized for 5 days. Receives: Other: Contralateral active leg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Integrated ribonucleic acid (RNA) synthesis
deuterium oxide coupled with muscle biopsies
Measured: 5 days
Intramuscular protein signaling response to protein ingestion
muscle biopsies to assess protein signaling response to consuming 25 g of whey protein
Measured: 90 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2024
- Study start20 Feb 2024
- Primary completion1 Oct 2024
- Study completion1 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atrophy, DisuseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- United States Army Research Institute of Environmental Medicine
- Sponsor type
- US federal agency
- Responsible party
- Principal investigator, Emily E. Howard, United States Army Research Institute of Environmental Medicine
- Investigators
- Emily E Howard, PhD, Principal investigator, US Army Research Institute of Environmental Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06228742
- Sponsor's protocol ID
- 24-02
- Status last verified
- Nov 2024
- First submitted
- 18 Jan 2024
- Last updated
- 2 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Molecular Regulation of Skeletal Muscle Anabolic Resistance to Dietary Protein in Response to Injury-mediated Muscle Disuse
- ClinicalTrials.gov ID
- NCT06228742
- Acronym / sponsor ID
- 24-02
- Conditions
- Atrophy, Disuse, Muscle Atrophy, Muscular Disorders, Atrophic, Disuse Atrophy, Disuse Atrophy Muscle of Thigh
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- United States Army Research Institute of Environmental MedicineUS federal agency
- Study start
- 20 Feb 2024 (actual)
- Primary completion
- 1 Oct 2024 (actual)
- Study completion
- 1 Oct 2024 (actual)
- First posted
- 29 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Warfighters that sustain musculoskeletal injuries often experience decreased muscle loading and activation post-injury (i.e., muscle disuse) that results in a rapid loss of muscle mass and function. Loss of muscle under these conditions is attributed to a persistent negative net muscle protein balance (muscle protein synthesis [MPS] < muscle protein breakdown [MPB]) that results, in part, from a blunting of MPS in the postprandial state. Nutritional interventions that optimize postprandial MPS have been suggested as countermeasures for this "anabolic resistance" that develops during disuse to preserve muscle mass and accelerate return to duty. However, a poor understanding of mechanisms underlying anabolic resistance during disuse has made it difficult to determine an optimal nutritional intervention. The current study will address this knowledge gap directly by characterizing intramuscular molecular mechanisms underlying anabolic resistance to protein ingestion during muscle disuse. Healthy, recreationally active men and women (n=12) will be studied using a within-subjects, unilateral design. After completing baseline measures of height, weight, and body composition, participants will begin a 3-day run-in phase where they will receive diet instructions (no food provided). Muscle disuse will then be implemented for 5 days using a unilateral leg immobilization model with one leg randomly assigned to immobilization and the contralateral, active leg used as a within-subjects control. Immobilization will be implemented using a rigid knee brace, and participants will ambulate using crutches. Diets will be standardized during the immobilization phase (1.0 g protein/kg/d, 30% of energy intake from fat, and the remaining calories from carbohydrate). 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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Immobilized Leg | Experimental | Other: Unilateral leg immobilizationOne leg of a young, healthy adult will be randomly assigned to undergo 5 days of immobilization using a rigid knee brace. |
| Non-immobilized leg | Experimental | Other: Contralateral active legOne leg of a young, healthy adult will remain active and not immobilized for 5 days. |
Who may qualify
- Ages
- 18 to 39 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (11 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Unilateral leg immobilizationAlso: DISUSEParticipants 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. | Other | Immobilized Leg |
| Contralateral active legAlso: ACTIVEOne leg will remain non-immobilized and active during the study. Participants will use this leg to walk with crutches. | Other | Non-immobilized leg |
Primary outcome
Integrated ribonucleic acid (RNA) synthesis
Time frame: 5 days
deuterium oxide coupled with muscle biopsies
Intramuscular protein signaling response to protein ingestion
Time frame: 90 minutes
muscle biopsies to assess protein signaling response to consuming 25 g of whey protein
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2024.
- Individual participant dataSharing planned: No
Related trials for Atrophy, Disuse
Not yet recruiting
Effect of Knee Position on Muscle Loss During Leg Immobilization
Muscle Atrophy, Disuse Atrophy
Active, not recruiting
Sex-specific Determinants of Early-phase Recovery From Skeletal Muscle Disuse
Atrophy of Muscle Due to Disuse, Rehabilitation
Not yet recruiting
Cross-education of Skill and Strength in Healthy People Subjected to an Upper-limb Disuse Model
Disuse Atrophy, Immobilization
Recruiting
Effect of Dietary Nitrate on Immobilization-induced Changes in Skeletal Muscle in Young Healthy Men
Mitochondrial Energetics, Dietary Nitrate
Recruiting
Muscle Response to Different Amounts of Dietary Protein During Leg Immobilization
Muscle Disuse, Muscle Disuse Atrophy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Emily E Howard, PhD principal investigator
US Army Research Institute of Environmental Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Unilateral leg immobilization and Contralateral active leg in people with Atrophy, Disuse and Muscle Atrophy, run by United States Army Research Institute of Environmental Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Integrated ribonucleic acid (RNA) synthesis (time frame: 5 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2024; AzTrials last refreshed its copy on 7 Nov 2026.