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

NCT ID: NCT04151901

Last Updated: 2026-01-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-27
• Study Completion Date: 2026-12-31

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.

Detailed Description

The negative health consequences of muscular disuse in aging populations are unequivocal. While descriptive, outcome data on disuse and recovery are abundant, key knowledge gaps limit researcher's ability to implement evidence-based, rehabilitation strategies. Limiters include: i) an inability to identify individuals most susceptible to disuse, ii) insufficient information to differentiate between, and respond to, disuse atrophy in men and women, iii) limited insight into the mechanisms driving adaptation to early rehabilitative exercise, and iv) the assumption that disused and healthy skeletal muscle will have a similar, positive response to resistance exercise. The investigators will complete a 2-phase, randomized clinical trial. The protocol includes 7-days of unilateral leg disuse (ULD; Phase 1), immediately followed by 1 week of bilateral leg rehabilitation (Phase 2). Healthy, middle-aged men (n=40) and (post-menopausal) women (n=40), (50-65 y) will be recruited; a neglected research demographic who present with a largely youthful phenotype, but are at risk of accelerated disuse atrophy.

This project will provide a highly powered, detailed phenotypic characterization of the continuum of adults most and least susceptible to muscular disuse. Clinical outcomes will be supported by RNA deep sequencing and pathway analysis to establish a platform that: i) improves scientists' ability to identify higher-risk individuals and ii) provides insight into time-sensitive, sex-specific and effective rehabilitation strategies. Findings and reposed molecular data from this study, may help identify future therapeutic targets and serve as an uncomplicated/comorbidity-free baseline for clinical trials in populations experiencing disuse atrophy.

Conditions

Atrophy of Muscle Due to Disuse; Rehabilitation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: OTHER
• Blinding Strategy: SINGLE

Study Groups

Male Rehabilitation (M-REHAB)

Disuse + resistance exercise rehabilitation

Group Type: EXPERIMENTAL

Resistance Exercise Rehabilitation

Intervention Type: 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.

Male Control (M-CON)

Disuse + ambulatory control rehabilitation

Group Type: EXPERIMENTAL

Walking-based rehabilitation

Intervention Type: 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 Rehabilitation (F-REHAB)

Disuse + resistance exercise rehabilitation

Group Type: EXPERIMENTAL

Resistance Exercise Rehabilitation

Intervention Type: 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 Control (F-CON)

Disuse + ambulatory control rehabilitation

Group Type: EXPERIMENTAL

Walking-based rehabilitation

Intervention Type: 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.

Interventions

Resistance Exercise Rehabilitation

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.

Intervention Type: OTHER

Walking-based rehabilitation

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

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. All races and ethnic backgrounds

2. Men and women, age 50-65 years

Exclusion Criteria

4. Able and willing to provide informed consent

5. Ability to speak and read English

6. Post-menopausal women (no menses within the last 12 months)

7. Body mass index: 18.5-35 kg/m2 or BMI>35 if thigh adiposity does not impair muscle biopsy

1. Compromised musculoskeletal function that precludes safe participation or use of crutches

2. Pre-menopausal women

3. Hypogonadal men (testosterone <300 ng/dL)

4. Women taking hormone replacement therapy (HRT)

5. Sarcopenia (European Working Group on Sarcopenia in Older People, EWGSOP102)

6. Clinically significant heart disease (e.g. New York Heart Classification greater than grade II; ischemia)

7. Peripheral vascular disease

8. History of claudication

9. Pulmonary disease

10. History of systemic or pulmonary embolus

11. Uncontrolled blood pressure (systolic BP>170, diastolic BP>95 mmHg)

12. Impaired renal function (creatinine >1.5 mg/dl)

13. Anemia (hematocrit <33)

14. Untreated thyroid disease (abnormal TSH)

15. A recent history (<12 months) of GI bleed

16. Diabetes mellitus or other untreated endocrine or metabolic disease

17. Electrolyte abnormalities

18. Any history of stroke, hypo- or hyper-coagulation disorders

19. Employment requiring long (>1 h) uninterrupted period of standing

20. Inability to meet study travel requirements (e.g. manual geared car)

21. Recent history of balance issues or falls.

22. Recent (3 years) treated cancer other than basal cell carcinoma

23. Systemic steroids, anabolic steroids, growth hormone or immunosuppressant use within 12 months

24. Recent (2 months) adherence to a weight-loss or weight-gain diet

25. Weight change of 5% or more in previous 6 months

26. Body mass index >30 or excess body fat that compromises muscle biopsy collection

27. Acute infectious disease or chronic infection

28. Alcohol or drug abuse

29. Any other condition or event considered exclusionary by study physician

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

The University of Texas Health Science Center at San Antonio

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Blake Rasmussen, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Texas Health Science Center as San Antonio

Locations

University of Texas Medical Branch

Galveston, Texas, United States

Site Status: COMPLETED

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Blake Rasmussen, PhD

Role: CONTACT

rasmussenb@uthscsa.edu

210-450-7491

Sean Kilroe, PhD

Role: CONTACT

kilroe@uthscsa.edu

Facility Contacts

Blake Rasmussen, PhD

Role: primary

rasmussenb@uthscsa.edu

210-450-7491

Sean Kilroe, PhD

Role: backup

kilroe@uthscsa.edu

Other Identifiers

R01AG064386

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HSC20230594H

Identifier Type: -

Identifier Source: org_study_id