Rehabilitation for Disuse Atrophy

(MAC Trial)

Overseen By Sean Kilroe, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The University of Texas Medical Branch, Galveston

Must not be taking: Hormone therapy, Steroids, Immunosuppressants, others

Disqualifiers: Heart disease, Diabetes, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines muscle changes in middle-aged men and post-menopausal women when one leg remains unused for a week, followed by a week of exercise for both legs. Researchers aim to understand how disuse and exercise affect muscles differently based on sex and to identify key factors that make muscles susceptible to shrinking. Participants will engage in either resistance exercises (resistance exercise rehabilitation) or walking-based rehabilitation to assess muscle recovery. The study seeks healthy men and post-menopausal women from the Houston/Galveston area who are generally active and do not have significant health issues. As an unphased trial, it offers participants the chance to contribute to foundational research that could enhance understanding of muscle health.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are using systemic steroids, anabolic steroids, growth hormone, or immunosuppressants, you must not have used them within the last 12 months to be eligible.

What prior data suggests that this rehabilitation protocol is safe?

Research shows that resistance exercise and walking-based rehabilitation are generally safe and well-tolerated. Studies have found that resistance exercise helps prevent muscle loss from inactivity. For example, an 11-day rehabilitation program safely and effectively reversed muscle loss caused by bed rest. Resistance training also helps older adults build muscle and prevent muscle loss.

Walking-based rehabilitation is considered safe. Exercise programs that include walking offer a safe and non-invasive way to address muscle loss. Combining everyday activities with walking has significantly improved muscle function.

Both treatments in this trial aim to help regain muscle strength after periods of inactivity. Research suggests these methods are not only effective but also safe for healthy middle-aged individuals. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these rehabilitation methods for disuse atrophy because they offer targeted approaches to muscle recovery. Traditional treatments often focus on general physical therapy and rest, but these methods prioritize specific types of rehabilitation: resistance exercise and walking-based routines. The resistance exercise approach is designed to directly counteract muscle loss by building strength and mass, while the walking-based method emphasizes improving cardiovascular health and mobility. By tailoring the rehabilitation to different genders and focusing on distinct exercise regimens, these techniques aim to enhance recovery outcomes more effectively than standard care options.

What evidence suggests that this trial's treatments could be effective for disuse atrophy?

This trial will compare two rehabilitation methods for disuse atrophy: resistance exercise rehabilitation and walking-based rehabilitation. Studies have shown that resistance exercise helps prevent muscle loss during inactivity, increasing the size and strength of muscles used for standing and walking. Other research indicates that resistance training is as effective as aerobic exercise in preventing muscle weakness in older adults. Walking-based rehabilitation also enhances muscle strength and balance, crucial for preventing falls and muscle loss. Both methods are safe and can significantly aid in maintaining muscle health during recovery. ^{1 4 5 6 7}

Who Is on the Research Team?

Blake Rasmussen, PhD

Principal Investigator

University of Texas Health Science Center as San Antonio

Are You a Good Fit for This Trial?

Healthy men and women aged 50-65 in the Houston/Galveston area can join this trial. They must be able to consent, speak English, and not have conditions like sarcopenia, severe heart disease, recent eating disorders or significant weight changes. Women should be post-menopausal and men must not have low testosterone levels.

Inclusion Criteria

People of all races and ethnicities are welcome to participate.

I am between 50 and 65 years old.

Generally healthy (see exclusion criteria)

Exclusion Criteria

Untreated thyroid disease (abnormal TSH)

I have a lung condition.

You have a high body mass index (BMI) or excess body fat that makes it difficult to collect a muscle biopsy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Unilateral Leg Disuse

Participants undergo 7 days of unilateral leg disuse to study the effects of skeletal muscle atrophy

1 week

Daily monitoring (in-person)

Bilateral Leg Rehabilitation

Participants engage in 14 days of bilateral leg rehabilitation to map the early, sex-specific molecular time-course of recovery

2 weeks

Daily sessions (in-person)

Follow-up

Participants are monitored for safety and effectiveness after rehabilitation

1 week

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Resistance Exercise Rehabilitation
• Walking-based rehabilitation

Trial Overview The study tests how middle-aged men's and women's muscles recover from a week of leg disuse followed by two weeks of rehabilitation using resistance exercise or walking-based rehab. It aims to understand sex-specific responses during muscle atrophy and recovery.

How Is the Trial Designed?

Group I: Male Rehabilitation (M-REHAB) Experimental Treatment 1 Intervention

Disuse + resistance exercise rehabilitation

Group II: Male Control (M-CON) Experimental Treatment 1 Intervention

Disuse + ambulatory control rehabilitation

Group III: Female Rehabilitation (F-REHAB) Experimental Treatment 1 Intervention

Disuse + resistance exercise rehabilitation

Group IV: Female Control (F-CON) Experimental Treatment 1 Intervention

Disuse + ambulatory control rehabilitation

Who Is Running the Clinical Trial?

The University of Texas Medical Branch, Galveston

Lead Sponsor

Trials

263

Recruited

55,400+

The University of Texas Health Science Center at San Antonio

Lead Sponsor

Trials

486

Recruited

92,500+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

Early rehabilitation with balance and gait exercises during the acute to subacute recovery phase after a stroke significantly improves balance and walking capacity, based on a review of 17 randomized clinical trials.

Engaging in at least 1 hour of balance training and 30 minutes of gait-oriented exercise, three to five times per week, is effective for stroke survivors, suggesting a combination of these exercises is optimal for recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of exercise-based rehabilitation on balance and gait for stroke patients: a systematic review. An, M., Shaughnessy, M.[2018]

Resistance exercise (RE) is a promising approach to combat disuse-induced skeletal muscle atrophy, showing positive effects on both muscle strength and structural changes, based on various human and animal studies.

The effectiveness of RE can be influenced by several factors such as volume, frequency, intensity, and type of muscle action, highlighting the need for controlled studies to better understand its impact on muscle remodeling and function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional and morphological effects of resistance exercise on disuse-induced skeletal muscle atrophy. Nicastro, H., Zanchi, NE., Luz, CR., et al.[2019]

A rehabilitation program for 21 inpatients with multiple sclerosis led to significant improvements in balance, gait speed, and lower limb strength, as measured before and after the program.

The study demonstrated that patients not only improved their balance and walking speed but also showed enhanced strength in their quadriceps and hamstrings, indicating the effectiveness and safety of rehabilitation for MS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Strength, postural and gait changes following rehabilitation in multiple sclerosis: a preliminary study]. Cantalloube, S., Monteil, I., Lamotte, D., et al.[2019]

A study comparing eccentric resistance exercise (RENEW) and traditional resistance exercise (TRAD) in high fall risk older adults showed no significant differences in improving mobility, balance confidence, muscle power, or cross-sectional area over a year-long period.

Despite both exercise methods not showing differential effects, the multi-component exercise fall reduction program led to a significant decrease in fall incidents, with less than 50% of participants experiencing a fall or near-fall after 3 months of exercise and 9 months of follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eccentric versus traditional resistance exercise for older adult fallers in the community: a randomized trial within a multi-component fall reduction program. LaStayo, P., Marcus, R., Dibble, L., et al.[2018]

In a randomized controlled trial involving 209 elderly participants (average age 80), a home-based exercise program was found to be generally safe, with 151 adverse events reported, affecting 47% of participants.

Despite the program's safety, 14% of the adverse events were serious, highlighting that high levels of pre-existing morbidity in this population can pose challenges to maintaining consistent exercise participation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in mobility-limited and chronically ill elderly adults participating in an exercise intervention study supported by general practitioner practices. Hinrichs, T., Bücker, B., Wilm, S., et al.[2015]

Resistance training (RT) is effective in increasing muscle mass and strength, but older adults (ages 60-75) need a higher maintenance dose compared to younger adults (ages 20-35) to sustain these gains after an initial training period.

In a study with 70 participants, while younger adults maintained muscle hypertrophy with reduced training, older adults did not; however, strength levels in older adults remained comparable to those of untrained younger individuals, indicating that strength gains are more easily preserved than muscle size.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise dosing to retain resistance training adaptations in young and older adults. Bickel, CS., Cross, JM., Bamman, MM.[2022]

Current guidelines for resistance exercise in cardiac rehabilitation are too restrictive, which can hinder patients' recovery and ability to engage in daily activities after cardiac events.

The study proposes a new method for prescribing resistance exercises that assesses the risk of 13 common exercises for different cardiac conditions, aiming to enhance safety and efficacy in rehabilitation, ultimately improving patient satisfaction and reducing dropout rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new paradigm for post-cardiac event resistance exercise guidelines. Adams, J., Cline, MJ., Hubbard, M., et al.[2007]

A comprehensive review of literature on sarcopenia rehabilitation highlighted that exercise and dietary supplementation are essential components for effective treatment, supported by numerous guidelines and systematic reviews.

Personalized rehabilitation management for sarcopenia should include tailored exercise programs and nutritional support to enhance the autonomy and safety of elderly patients, focusing on flexibility, balance, and coordination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rehabilitative Good Practices in the Treatment of Sarcopenia: A Narrative Review. Agostini, F., Bernetti, A., Di Giacomo, G., et al.[2023]

A comprehensive review of amputee rehabilitation highlights the importance of structured exercise programs that focus on flexibility, muscle strength, cardiovascular fitness, and balance to aid recovery and reintegration into daily life.

Rehabilitation involves a multidisciplinary approach, incorporating physical, occupational, and recreational therapy, all guided by a physician to ensure effective recovery and adaptation for amputees.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rehabilitation after amputation. Esquenazi, A., DiGiacomo, R.[2022]

Participants with chronic health conditions expressed that adverse events (AEs) from resistance training (RT) significantly impact their willingness to engage in future exercise, highlighting the importance of understanding both the risks and benefits of RT.

The study identified that personal experiences, health conditions, and the environment in which RT occurs influence perceptions of safety and participation, suggesting that better communication about the risks of AEs is essential to encourage RT among individuals with chronic health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring participants' perspectives on adverse events due to resistance training: a qualitative study. El-Kotob, R., Pagcanlungan, JR., Craven, BC., et al.[2023]

A systematic review of 12 randomized controlled trials involving older adults indicates that resistance training (RT) significantly improves gait and balance, particularly enhancing straight-line walking speed.

The improvements in strength from RT may lead to greater autonomy and independence in daily activities for the aging population, highlighting its importance as an effective intervention for older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of Resistance Training on Gait & Balance Parameters in Older Adults: A Systematic Review. Keating, CJ., Cabrera-Linares, JC., Párraga-Montilla, JA., et al.[2022]

Research indicates that the amount, intensity, and variability of practice during rehabilitation can significantly impact walking recovery in stroke patients, suggesting that tailored training parameters are crucial for effective rehabilitation.

Different patient factors, such as the severity of the stroke and individual impairments, may affect how these training variables contribute to recovery, highlighting the need for personalized rehabilitation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of skill and exercise training parameters on locomotor recovery during stroke rehabilitation. Hornby, TG., Moore, JL., Lovell, L., et al.[2020]

Physical strategies, such as resistance exercises and aerobic activities, are effective in preventing functional decline and muscle atrophy in elderly patients during disuse situations, particularly in hospitals.

Alternative methods like neuromuscular electrical stimulation and blood flow restriction can also help, especially for those unable to perform traditional exercises, but work best when combined with voluntary exercise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical strategies to prevent disuse-induced functional decline in the elderly. Valenzuela, PL., Morales, JS., Pareja-Galeano, H., et al.[2019]

A set of therapeutic exercises, including swimming and loading exercises, has been shown to enhance strength and performance in both the amputated and supporting limbs of patients recovering from lower limb amputation.

The effectiveness of these exercises was assessed using dynamometry and ultrasound osteometry, demonstrating improvements in muscle strength and a reduction in osteoporosis of the stump bone fragment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic physical exercise for patients after the amputation of the lower extremities at the sanatorium stage of rehabilitation]. Epifanov, VA., Kovalenko, EV.[2022]

Using high-resolution real-time ultrasonography (HRRTU), the study found significant muscle atrophy in the quadriceps of 13 male patients with immobilized limbs due to fractures, evidenced by changes in muscle architecture such as decreased pennation angle and muscle fiber length.

The results indicate that HRRTU is a reliable, non-invasive method to assess muscle changes, which could help in tailoring rehabilitation exercises for patients recovering from limb immobilization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound changes to intramuscular architecture of the quadriceps following intramedullary nailing. Bleakney, R., Maffulli, N.[2017]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39920735/

a meta-analysis of randomized controlled trials Resistance exercise training improves disuse-induced skeletal muscle atrophy in humans: a meta-analysis of randomized controlled trials.

2. bmcmusculoskeletdisord.biomedcentral.com bmcmusculoskeletdisord.biomedcentral.com/articles/10.1186/s12891-025-08384-7

Resistance exercise training improves disuse-induced ... RET effectively minimized deterioration of muscle volume and muscle function during immobilization/disuse, particularly in anti-gravitational muscles.

3. sciencedirect.com sciencedirect.com/science/article/pii/S2666337625000216

Resistance exercise alleviates skeletal muscle atrophy ... Here we show that six-week resistance exercise training significantly improved muscle function, muscle mass, and oxidative damage and maintained the level of ...

4. physoc.onlinelibrary.wiley.com physoc.onlinelibrary.wiley.com/doi/10.1113/EP091937

Mitigating disuse‐induced skeletal muscle atrophy in ageing ... Recent evidence suggests RT can be as effective as aerobic exercise in reducing cancer risks, delaying mortality, mitigating the progression of ...

5. nature.com nature.com/articles/s41598-025-11076-w

Effects of resistance training and aerobic ... Studies underline the efficacy of resistance training in preventing muscle atrophy and enhancing various physical attributes. Resistance ...

6. journals.lww.com journals.lww.com/nsca-jscr/fulltext/2019/08000/resistance_training_for_older_adults__position.1.aspx

Resistance Training for Older Adults: Position Statement... Current research has demonstrated that countering muscle disuse through resistance training is a powerful intervention to combat muscle strength loss, muscle ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7688251/

Disuse-Induced Muscle Loss and Rehabilitation Bed rest results in upper and lower leg muscle atrophy in a linear pattern, and an 11-day rehabilitation program was safe and effective.