Sex-specific Determinants of Early-phase Recovery From Skeletal Muscle Disuse

NCT04151901 | Recruiting DMC

• 2 other identifiers: HSC20230594HR01AG064386
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 2

Brief Summary

This project is a 2-phase, randomized clinical trial that includes 7 days of unilateral leg disuse (Phase 1), immediately followed by 1 week of bilateral leg rehabilitation (Phase 2). The investigators will recruit cohorts of healthy middle-aged men and women to address their aims:

• Demonstrate the sex-specific effects of skeletal muscle disuse (Phase 1)
• Identify key molecular determinates of susceptibility of skeletal muscle atrophy (Phase 1)
• Map the early, sex-specific molecular time-course of rehabilitation (Phase 2)
• Determine if disused and healthy muscle respond similarly to exercise (Phase 2) Healthy, middle-age men and post-menopausal women (50-65 years) will be recruited from the greater Houston/Galveston area. This under-represented research demographic demonstrate few negative metabolic or phenotypic signs of advanced age, but are at increased risk of being hospitalized and experiencing accelerated loss of lean mass and muscle function that parallels a much older population. The goal of this study is to characterize phenotypic and molecular skeletal muscle changes in middle-aged men and women during critical periods of disuse and rehabilitation and ultimately direct the development of targeted and effective prevention and treatment strategies.

Conditions

Atrophy of Muscle Due to Disuse; Rehabilitation

Outcome Measures

Primary Outcomes (16)

• Quantitative RNA-sequencing

  RNA deep sequence analysis on muscle tissue taken from a muscle biopsy to measure transcriptome

  Study day 1 (before starting leg disuse)

• Quantitative RNA-sequencing

  RNA deep sequence analysis on muscle tissue taken from a muscle biopsy to measure transcriptome

  Study day 7 (after finishing leg disuse)

• Quantitative RNA-sequencing

  RNA deep sequence analysis on muscle tissue taken from a muscle biopsy to measure transcriptome

  Study day 7 (after 1 bout of rehabilitation)

• Quantitative RNA-sequencing

  RNA deep sequence analysis on muscle tissue taken from a muscle biopsy to measure transcriptome

  Study day 9 (after 2 bouts of rehabilitation)

• Quantitative RNA-sequencing

  RNA deep sequence analysis on muscle tissue taken from a muscle biopsy to measure transcriptome

  Study Day 11 (after 3 bouts of rehabilitation)

• Quantitative RNA-sequencing

  RNA deep sequence analysis on muscle tissue taken from a muscle biopsy to measure transcriptome

  Study Day 21 (after finishing 7 bouts of rehabilitation)

• Muscle function

  Each leg will be individually tested on an isokinetic dynamometer to determine muscle strength (peak torque)

  Study day 1 (before starting leg disuse)

• Muscle function

  Each leg will be individually tested on an isokinetic dynamometer to determine muscle strength (peak torque)

  Study day 7 (after 1 bout of rehabilitation)

• Muscle function

  Each leg will be individually tested on an isokinetic dynamometer to determine muscle strength (peak torque)

  Study day 9 (after 2 bouts of rehabilitation)

• Muscle function

  Each leg will be individually tested on an isokinetic dynamometer to determine muscle strength (peak torque)

  Study Day 11 (after 3 bouts of rehabilitation)

• Muscle function

  Each leg will be individually tested on an isokinetic dynamometer to determine muscle strength (peak torque)

  Study Day 21 (after finishing 7 bouts of rehabilitation)

• Body (leg) composition

  Leg lean mass will be assessed via segmental dual energy x-ray absorptiometry

  Study day 1 (before starting leg disuse)

• Body (leg) composition

  Leg lean mass will be assessed via segmental dual energy x-ray absorptiometry

  Study day 7 (after finishing leg disuse)

• Body (leg) composition

  Leg lean mass will be assessed via segmental dual energy x-ray absorptiometry

  Study day 9 (after 2 bouts of rehabilitation)

• Body (leg) composition

  Leg lean mass will be assessed via segmental dual energy x-ray absorptiometry

  Study Day 11 (after 3 bouts of rehabilitation)

• Body (leg) composition

  Leg lean mass will be assessed via segmental dual energy x-ray absorptiometry

  Study Day 21 (after finishing 7 bouts of rehabilitation)

Secondary Outcomes (15)

• Muscle fiber cross sectional area

  Study day 1 (before starting leg disuse)

• Muscle fiber cross sectional area

  Study day 7 (after finishing leg disuse)

• Muscle fiber cross sectional area

  Study day 9 (after 2 bouts of rehabilitation)

• Muscle fiber cross sectional area

  Study Day 11 (after 3 bouts of rehabilitation)

• Muscle fiber cross sectional area

  Study Day 21 (after finishing 7 bouts of rehabilitation)

Study Arms (4)

Male Rehabilitation (M-REHAB)

EXPERIMENTAL

Disuse + resistance exercise rehabilitation

Other: Resistance Exercise Rehabilitation

Male Control (M-CON)

EXPERIMENTAL

Disuse + ambulatory control rehabilitation

Other: Walking-based rehabilitation

Female Rehabilitation (F-REHAB)

EXPERIMENTAL

Disuse + resistance exercise rehabilitation

Other: Resistance Exercise Rehabilitation

Female Control (F-CON)

EXPERIMENTAL

Disuse + ambulatory control rehabilitation

Other: Walking-based rehabilitation

Interventions

Resistance Exercise Rehabilitation OTHER

Following disuse, the REHAB groups (M-REHAB, F-REHAB) will complete monitored resistance exercise rehabilitation sessions using an isokinetic dynamometer at a similar relative load at each rehab visit.

Female Rehabilitation (F-REHAB); Male Rehabilitation (M-REHAB)

Walking-based rehabilitation OTHER

Following disuse, the CON groups (M-CON, F-CON) will complete 30 minutes of monitored walking at a moderate intensity at each rehab visit.

Female Control (F-CON); Male Control (M-CON)

Eligibility Criteria

• Age: 50 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All races and ethnic backgrounds
• Men and women, age 50-65 years

You may not qualify if:

• Able and willing to provide informed consent
• Ability to speak and read English
• Post-menopausal women (no menses within the last 12 months)
• Body mass index: 18.5-35 kg/m2 or BMI\>35 if thigh adiposity does not impair muscle biopsy
• Compromised musculoskeletal function that precludes safe participation or use of crutches
• Pre-menopausal women
• Hypogonadal men (testosterone \<300 ng/dL)
• Women taking hormone replacement therapy (HRT)
• Sarcopenia (European Working Group on Sarcopenia in Older People, EWGSOP102)
• Clinically significant heart disease (e.g. New York Heart Classification greater than grade II; ischemia)
• Peripheral vascular disease
• History of claudication
• Pulmonary disease
• History of systemic or pulmonary embolus
• Uncontrolled blood pressure (systolic BP\>170, diastolic BP\>95 mmHg)

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead
• National Institute on Aging (NIA): collaborator

Study Sites (2)

University of Texas Medical Branch

Galveston, Texas, 77555, United States

COMPLETED

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

MeSH Terms

Conditions

Muscular Disorders, Atrophic

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases

Study Officials

• Blake Rasmussen, PhD

  University of Texas Health Science Center as San Antonio

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Blake Rasmussen, PhD

CONTACT

210-450-7491; rasmussenb@uthscsa.edu

Sean Kilroe, PhD

CONTACT

kilroe@uthscsa.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2019
• First Posted: November 5, 2019
• Study Start: August 27, 2021
• Primary Completion: April 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be shared at study completion as summary results on ClinicalTrials.gov and after review and publication in a peer-reviewed journal.

Locations

US (2)