Exercise and Bracing for Muscle Atrophy

(HYPAT Trial)

Age: 18 - 65

Sex: Male

Trial Phase: Academic

Sponsor: McMaster University

Must not be taking: Glucocorticoids, NSAIDs, Acne medication, Anticoagulants

Disqualifiers: Neuromuscular disorders, Diabetes, Hypertension, Tobacco, others

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

Compensation: Varies

Number of Visits: 7

16 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

If you are taking medications that affect protein metabolism, like glucocorticoids or certain anti-inflammatory drugs, you will need to stop them to participate in this trial.

What data supports the effectiveness of the treatment Knee bracing, Unilateral Resistance Exercise Training for muscle atrophy?

Research shows that strength training can increase muscle strength by 19 to 34% in trained limbs, suggesting that resistance exercise, a component of the treatment, may help manage muscle atrophy. Additionally, resistance training is known to aid recovery from muscle atrophy, indicating potential benefits of this treatment approach. ^{1 2 3 4 5}

Is resistance exercise training safe for humans?

Resistance exercise training is generally considered safe for humans and is associated with various health benefits, including improved muscle strength and reduced risk of diseases. Minimal-dose resistance training approaches may also limit discomfort and increase enjoyment, potentially improving adherence to exercise routines. ^{6 7 8 9 10}

How does Unilateral Resistance Exercise Training differ from other treatments for muscle atrophy?

Unilateral Resistance Exercise Training is unique because it focuses on strengthening one side of the body at a time, which can lead to greater strength gains in the trained limb and also improve strength in the untrained limb through a phenomenon called cross-education. This approach can be more effective than bilateral training (training both sides together) for specific strength improvements. ^{3 11 12 13 14}

What is the purpose of this trial?

Skeletal muscle plays several different roles in the promotion and maintenance of health and well-being. The loss of muscle mass that occurs with aging, chronic muscle wasting diseases, and physical inactivity puts people at an increased risk of frailty and becoming insulin resistant, and therefore imposes a significant burden on health care spending. Resistance exercise participation has proven particularly effective for increasing muscle mass and strength. This effectiveness can be used by health care practitioners in a rehabilitation setting to promote the recovery of individuals who have undergone involuntary periods of muscular unloading (i.e. limb immobilization caused by a sports injury or reconstructive surgery). However, there is large variability in the amount of muscle mass and strength that people gain following participation in resistance exercise. Some individuals fail to increase the size of their muscle (low responders) whereas others show vary large increases in muscle size (high responders) in response to the same resistance training program. People also show differences in the amount of muscle tissue they lose when they have a limb immobilized. To circumvent variability across individuals, the investigators utilized a within-person paired Hypertrophy and Atrophy ('HYPAT') strategy that reduced response heterogeneity by \~40% (Available at: https://ssrn.com/abstract=3445673). Specifically, one leg performed resistance training for 10 weeks to induce hypertrophy, whereas the other leg underwent single-leg immobilization for 2 weeks to induce atrophy. The primary goal of the study will be to gain insight into the molecular responses to an acute period of single-leg immobilization and resistance exercise (8 days). The investigators will use an integrated systems biology approach to monitor the individual rates of over one hundred different muscle proteins.

Eligibility Criteria

Healthy males aged 18-30 with a BMI of 18.5 to 30 can join this study. They must be able to consent and not have muscle or bone diseases, serious illnesses, uncontrolled hypertension, diabetes, or take meds affecting protein metabolism. Non-smokers who don't drink excessively or exercise more than twice a week are eligible.

Inclusion Criteria

I am a healthy male aged between 18 and 30.

Your body mass index (BMI) is between 18.5 and 30.0.

Able and willing to provide informed consent

Exclusion Criteria

I am taking blood thinners.

You use tobacco products.

You drink more than 21 units of alcohol per week.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Unilateral Resistance Exercise

One leg will undergo 4 sessions of unilateral resistance exercise, over the course of 8 days, including leg press and leg extension.

8 days

4 sessions (in-person)

Unilateral Immobilization

One leg will undergo 14 days of single-leg immobilization using a removable knee brace.

14 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of muscle protein synthesis, lean mass, muscle strength, and muscle cross-sectional area.

2 weeks

3 visits (in-person)

Treatment Details

Interventions

• Knee bracing
• Unilateral Resistance Exercise Training

Trial Overview The trial is testing the effects of knee bracing and unilateral resistance exercise training on muscle size changes due to loading (exercise) and unloading (immobilization). It aims to understand individual molecular responses over an acute period using advanced proteomics techniques.

Participant Groups

Group I: Unilateral Resistance Exercise Experimental Treatment 1 Intervention

One leg will undergo 4 sessions of unilateral resistance exercise, over the course of 8 days. Specifically, participants will be asked to perform leg press and leg extension.

Group II: Unilateral Immobilization Experimental Treatment 1 Intervention

One leg will undergo 14 days of single-leg immobilization, by means of a removable knee brace.

Who Is Running the Clinical Trial?

McMaster University

Lead Sponsor

Trials

936

Recruited

2,630,000+

Findings from Research

A 12-week home-based functional exercise program for individuals with spinal and bulbar muscular atrophy (SBMA) was well tolerated and did not result in significant improvements in overall muscle function or quality of life compared to a stretching control group of 50 participants.

However, a subgroup analysis revealed that low-functioning individuals in the functional exercise group showed improvements in specific functional scores, suggesting that targeted exercise may benefit certain patients and should be explored further.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial of exercise in spinal and bulbar muscular atrophy. Shrader, JA., Kats, I., Kokkinis, A., et al.[2018]

Resistance training at moderate intensities (40% and 60% of maximum contraction strength) is effective for promoting recovery from muscle atrophy in mice, as shown by improvements in muscle strength and myofiber size.

Training at very low (10%) or very high (90%) intensities did not support recovery, highlighting the importance of optimal training intensity for muscle regeneration and the role of myogenic satellite cells in muscle repair.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Training at non-damaging intensities facilitates recovery from muscle atrophy. Itoh, Y., Murakami, T., Mori, T., et al.[2018]

In a study of 24 patients with limb-girdle muscular dystrophy (LGMD), electrical stimulation significantly improved muscle strength in the Deltoideus compared to exercise therapy, with these benefits maintained during follow-up (p<0.05).

Overall, the electrical stimulation group showed greater improvements in muscle strength, endurance, and timed performance tests than the exercise therapy group, highlighting its potential as a more effective rehabilitation strategy for LGMD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of electrical stimulation and exercise therapy in patients with limb girdle muscular dystrophy. A controlled clinical trial. Kilinç, M., Yildirim, SA., Tan, E.[2018]

Resistance training (RT) is the only non-drug method proven to effectively counteract age-related declines in muscle mass, strength, and power, while also reducing risks of various health issues like cardiovascular disease and depression.

Minimal-dose RT strategies, which involve lower training volumes and can be performed with minimal equipment, are effective in improving strength and functional ability, making it easier for more people to participate and potentially enhancing overall health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minimal-Dose Resistance Training for Improving Muscle Mass, Strength, and Function: A Narrative Review of Current Evidence and Practical Considerations. Fyfe, JJ., Hamilton, DL., Daly, RM.[2022]

References

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

The effects of strength training in patients with selected neuromuscular disorders. [2019]

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

A randomized controlled trial of exercise in spinal and bulbar muscular atrophy. [2018]

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

Training at non-damaging intensities facilitates recovery from muscle atrophy. [2018]

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

An Overview of Muscle Atrophy. [2019]

5. Saudi Arabia pubmed.ncbi.nlm.nih.gov

The effects of electrical stimulation and exercise therapy in patients with limb girdle muscular dystrophy. A controlled clinical trial. [2018]

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

Hypertrophy of chronically unloaded muscle subjected to resistance exercise. [2022]

7. England pubmed.ncbi.nlm.nih.gov

High-intensity flywheel exercise and recovery of atrophy after 90 days bed--rest. [2022]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Minimal-Dose Resistance Training for Improving Muscle Mass, Strength, and Function: A Narrative Review of Current Evidence and Practical Considerations. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Randomized, four-arm, dose-response clinical trial to optimize resistance exercise training for older adults with age-related muscle atrophy. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

A Novel Amino Acid Composition Ameliorates Short-Term Muscle Disuse Atrophy in Healthy Young Men. [2020]

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

Age Does Not Attenuate Maximal Velocity Adaptations in the Ipsilateral and Contralateral Limbs During Unilateral Resistance Training. [2019]

12. Serbia pubmed.ncbi.nlm.nih.gov

The effect of whole-body vibration and resistance training on muscle strength in a 13-year-old boy with m. biceps femoris lesion and posttraumatic calcification. [2019]

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

Neuromuscular Adaptations to Unilateral vs. Bilateral Strength Training in Women. [2022]

14. England pubmed.ncbi.nlm.nih.gov

Cross-education and detraining effects of eccentric vs. concentric resistance training of the elbow flexors. [2021]