Trials / Completed
CompletedNCT06228742
Molecular Mechanisms Underlying Anabolic Resistance to Protein Intake During Muscle Disuse
Molecular Regulation of Skeletal Muscle Anabolic Resistance to Dietary Protein in Response to Injury-mediated Muscle Disuse
- Status
- Completed
- Phase
- N/A
- Study type
- Interventional
- Enrollment
- 12 (actual)
- Sponsor
- United States Army Research Institute of Environmental Medicine · Federal
- Sex
- All
- Age
- 18 Years – 39 Years
- Healthy volunteers
- Accepted
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.
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
Interventions
| Type | Name | Description |
|---|---|---|
| OTHER | Unilateral leg immobilization | 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. |
| OTHER | Contralateral active leg | One leg will remain non-immobilized and active during the study. Participants will use this leg to walk with crutches. |
Timeline
- Start date
- 2024-02-20
- Primary completion
- 2024-10-01
- Completion
- 2024-10-01
- First posted
- 2024-01-29
- Last updated
- 2024-12-02
Locations
1 site across 1 country: United States
Source: ClinicalTrials.gov record NCT06228742. Inclusion in this directory is not an endorsement.