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

Trial Summary

What is the purpose of this trial?

This project is a 2-phase, randomized clinical trial that includes 7 days of unilateral leg disuse (Phase 1), immediately followed by 14 days 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.

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 data supports the effectiveness of the treatment for Rehabilitation for Disuse Atrophy?

Research shows that resistance training can improve walking speed and balance in older adults, which suggests it may help with disuse atrophy by enhancing strength and independence. Additionally, exercise-based rehabilitation has been effective in improving balance and walking in stroke patients, indicating similar benefits could be expected for disuse atrophy. ^{1 2 3 4 5}

Is rehabilitation for disuse atrophy generally safe for humans?

Exercise therapies like resistance training and physical therapy are generally safe for humans, but there can be risks, especially for older adults or those with chronic health conditions. It's important to have medical clearance and trained supervision to minimize adverse events (unwanted side effects or injuries). ^{6 7 8 9 10}

How does this treatment for disuse atrophy differ from other treatments?

This treatment for disuse atrophy is unique because it focuses on resistance exercise, which helps improve muscle strength and size by using different types of exercises like flywheel and isometric exercises. Unlike other treatments, it emphasizes controlling exercise variables such as volume and intensity to effectively remodel and strengthen muscles. ^{11 12 13 14 15}

Research Team

Blake Rasmussen, PhD

Principal Investigator

University of Texas Health Science Center as San Antonio

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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]

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 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]

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 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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Influence of Resistance Training on Gait & Balance Parameters in Older Adults: A Systematic Review. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

[Strength, postural and gait changes following rehabilitation in multiple sclerosis: a preliminary study]. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Rehabilitative Good Practices in the Treatment of Sarcopenia: A Narrative Review. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

Influence of skill and exercise training parameters on locomotor recovery during stroke rehabilitation. [2020]

6. United States 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. [2015]

7. United States pubmed.ncbi.nlm.nih.gov

Exercise dosing to retain resistance training adaptations in young and older adults. [2022]

8. Canada pubmed.ncbi.nlm.nih.gov

Exploring participants' perspectives on adverse events due to resistance training: a qualitative study. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

A new paradigm for post-cardiac event resistance exercise guidelines. [2007]

10. England 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. [2018]

11. Brazil pubmed.ncbi.nlm.nih.gov

Functional and morphological effects of resistance exercise on disuse-induced skeletal muscle atrophy. [2019]

12. United States pubmed.ncbi.nlm.nih.gov

Rehabilitation after amputation. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Physical strategies to prevent disuse-induced functional decline in the elderly. [2019]

14. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Therapeutic physical exercise for patients after the amputation of the lower extremities at the sanatorium stage of rehabilitation]. [2022]

15. Italy pubmed.ncbi.nlm.nih.gov

Ultrasound changes to intramuscular architecture of the quadriceps following intramedullary nailing. [2017]