Exercise for Physical Activity Benefits

(MoTrMito Trial)

Overseen By Owen T Carmichael, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Pennington Biomedical Research Center

Must not be taking: Beta blockers, Anticoagulants, Antidepressants, others

Disqualifiers: Diabetes, Hypertension, Cancer, others

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

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether different types of exercise, such as aerobic or resistance training, can improve muscle cell function and overall metabolic health. The study examines people from various age groups to determine how exercise might enhance energy use in muscles, potentially leading to better health. Participants will perform isometric contraction exercises, which involve holding a muscle in a fixed position. This trial suits individuals who are generally healthy, not taking certain medications, and have a BMI between 19 and 35. As an unphased trial, it offers a unique opportunity to contribute to the scientific understanding of exercise's impact on health.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as lipid-lowering drugs, psychiatric drugs, and others listed in the exclusion criteria. If you are on any of these, you may need to stop them for at least 3 months before participating.

What prior data suggests that isometric contraction exercise is safe for improving mitochondrial capacity?

Research shows that isometric contraction exercises are generally safe for most people. These exercises involve tightening muscles without movement, such as pushing against a wall. Studies have found that they can slightly lower blood pressure, reducing the systolic number by about 7 points and the diastolic number by about 3 points.

Caution is important, as holding the breath or straining during these exercises might cause blood pressure to rise excessively. For those with a healthy heart, these exercises can temporarily increase heart rate and blood pressure.

Overall, isometric exercises are usually self-limiting, meaning people tend to stop before overexerting, which can enhance safety. If there are any health concerns, consulting a doctor before starting a new exercise routine is advisable. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about isometric contraction exercise because it offers a unique approach to improving physical activity benefits through non-invasive methods. Unlike traditional exercise routines that might focus on dynamic movements, isometric exercises involve muscle contractions without visible movement, which can be easier on the joints and accessible for a variety of age groups. By using 31P-Magnetic Resonance Spectroscopy, this method allows researchers to measure mitochondrial capacity in muscles, providing valuable insights into how exercise impacts cellular energy production. This could lead to more tailored exercise programs that maximize health benefits for different age groups.

What evidence suggests that isometric contraction exercise is effective for improving mitochondrial capacity?

Research has shown that isometric contraction exercises can enhance the energy-making ability of muscle cells. This trial will evaluate the effects of these exercises on different age groups. One study found that 12 weeks of resistance exercise altered muscle energy use, improving function. Another study found that active older adults have muscle energy levels similar to younger individuals. Additionally, isometric exercises, like high-intensity interval training (HIIT), can increase the number of energy-producing components in muscles and improve their function. These findings suggest that isometric contraction exercises could enhance energy use and physical ability for people of all ages. ^{6 7 8 9 10}

Who Is on the Research Team?

Owen T Carmichael, PhD

Principal Investigator

Director, Biomedical Imaging Center, PBRC

Are You a Good Fit for This Trial?

Healthy adults aged 18-39, 40-59, and over 60 with a BMI between >19 to <35 kg/m2 who can consent and understand English. Excluded are those on certain medications, planning weight changes, with chronic diseases like diabetes or heart conditions, high blood pressure or abnormal blood tests, recent substance abuse including tobacco and excessive alcohol intake.

Inclusion Criteria

I can read and speak English well enough to understand medical instructions.

I am 60 years old or older.

My BMI is between 19 and 35.

Exclusion Criteria

Hematocrit (screening test)

I am not taking any benzodiazepines.

I have been diagnosed with COPD.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Pre-training 31P MRS measurement to assess phosphocreatine recovery rate

1 week

1 visit (in-person)

Exercise Training

Participants undergo aerobic or resistance exercise training to improve mitochondrial capacity

12 weeks

Regular visits for exercise sessions

Post-training Assessment

Post-training 31P MRS measurement to assess changes in phosphocreatine recovery rate

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after exercise training

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Isometric Contraction Exercise

Trial Overview The study examines if aerobic or resistance exercise improves mitochondrial capacity in muscle cells across different age groups. It aims to see if these exercises affect metabolic health and functional capacity by changing how genes respond to exercise.

How Is the Trial Designed?

Group I: Young Adults (Age group 18-39) Active Control 1 Intervention

31P-Magnetic Resonance Spectroscopy exam on one thigh to measure mitochondrial capacity non-invasively after exercise training.

Group II: Middle Aged Adults (Age group 40-59) Active Control 1 Intervention

31P-Magnetic Resonance Spectroscopy exam on one thigh to measure mitochondrial capacity non-invasively after exercise training.

Group III: Old Adults (Age group >60) Active Control 1 Intervention

31P-Magnetic Resonance Spectroscopy exam on one thigh to measure mitochondrial capacity non-invasively after exercise training.

Who Is Running the Clinical Trial?

Pennington Biomedical Research Center

Lead Sponsor

Trials

314

Recruited

183,000+

AdventHealth Translational Research Institute

Collaborator

Trials

51

Recruited

5,900+

Stanford University

Collaborator

Trials

2,527

Recruited

17,430,000+

Wake Forest University Health Sciences

Collaborator

Trials

1,432

Recruited

2,506,000+

University of Colorado, Denver

Collaborator

Trials

1,842

Recruited

3,028,000+

University of Pittsburgh

Collaborator

Trials

1,820

Recruited

16,360,000+

The University of Texas Health Science Center at San Antonio

Collaborator

Trials

486

Recruited

92,500+

Published Research Related to This Trial

In a study involving 91 patients with chronic midportion Achilles tendinopathy, isometric exercises did not provide any immediate pain relief during a functional task, as measured by a visual analogue scale (VAS).

The results suggest that isometric exercises should not be recommended for immediate analgesic benefit in this patient population, although all exercise protocols were well-tolerated and may warrant further investigation for long-term treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isometric exercises do not provide immediate pain relief in Achilles tendinopathy: A quasi-randomized clinical trial. van der Vlist, AC., van Veldhoven, PLJ., van Oosterom, RF., et al.[2021]

The MoVe ICU study will evaluate the effects of early rehabilitation using a bedside cycle ergometer on muscle morphology in 28 critically ill patients on mechanical ventilation, aiming to minimize neuromuscular complications from prolonged immobilization.

This study is significant as it will be the first randomized controlled trial to assess whether passive cycling can preserve the structure of key muscles, like the knee extensors and diaphragm, in ICU patients, potentially improving their recovery outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early rehabilitation using a passive cycle ergometer on muscle morphology in mechanically ventilated critically ill patients in the Intensive Care Unit (MoVe-ICU study): study protocol for a randomized controlled trial. dos Santos, LJ., de Aguiar Lemos, F., Bianchi, T., et al.[2018]

Prior muscle contractions that involve lengthening or shortening can significantly affect cardiovascular responses during isometric exercise, as shown in two studies with 20 and 14 participants respectively.

During high-intensity isometric contractions, heart rate responses were lower when preceded by lengthening contractions (residual force enhancement), indicating that the type of prior muscle contraction can modulate cardiovascular responses, particularly under varying intensities and durations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular responses during isometric exercise following lengthening and shortening contractions. Seed, JD., St Peters, B., Power, GA., et al.[2020]

Regular physical exercise, including aerobic activities like walking and running, significantly improves cardiovascular health and reduces the risk of chronic diseases such as diabetes and heart disease.

Engaging in at least 150 minutes of moderate exercise per week, like brisk walking, not only aids in weight management and insulin sensitivity but also enhances mental well-being by reducing anxiety and stress.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regular physical exercise: way to healthy life. Siddiqui, NI., Nessa, A., Hossain, MA.[2022]

Static exercise, such as weight training, can lead to significant increases in blood pressure and heart rate, but is generally safe for healthy individuals and those with normal heart function.

People with impaired left ventricular function may experience negative cardiovascular effects from static exercise, including increased heart rate and blood pressure, which can lead to decreased heart performance if the exercise continues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Static exercise--physiologic dangers and proper training techniques. Stopford, JL.[2008]

Isometric exercise can safely increase blood pressure and maintain cardiac function in individuals with mild left ventricular impairment, making it a viable option for cardiac rehabilitation.

Patients recovering from myocardial infarction can perform submaximum isometric exercises without adverse effects, suggesting that isometric training should be incorporated into rehabilitation programs for those returning to jobs requiring such physical activities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isometric exercise: cardiovascular responses in normal and cardiac populations. Hanson, P., Nagle, F.[2008]

Isometric exercises at submaximal intensity (60% of maximal voluntary contraction) can still lead to a significant increase in both systolic and diastolic blood pressure immediately after the exercises.

Blood pressure levels return to normal within 30 minutes after performing these isometric exercises, indicating a temporary but notable effect on cardiovascular response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The effect of isometric exercises for cervical spine on blood pressure]. Curković, B., Puksec, M., Perić, P., et al.[2009]

Isometric exercise training (IET) significantly reduced resting blood pressure in a study of 30 physically inactive individuals, demonstrating its effectiveness as an antihypertensive intervention.

The IET group showed notable improvements in heart rate variability, indicating enhanced cardiac autonomic modulation, while the sham group did not experience these benefits, confirming that the effects of IET are not due to a placebo effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood pressure and cardiac autonomic adaptations to isometric exercise training: A randomized sham-controlled study. Decaux, A., Edwards, JJ., Swift, HT., et al.[2022]

Isometric muscle contractions lasting six seconds, performed once daily, can help patients with low cardiac reserve or severe debility improve their muscle strength by up to 2% per day, making it a viable option for those unable to engage in traditional exercise.

This technique is particularly beneficial for individuals with deconditioned muscles due to immobilization, although it does not lead to significant muscle growth, and could be integrated into treatment plans for various medical conditions like poliomyelitis and cardiac diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic exercise in general practice. RODRIGUEZ, MJ.[2018]

A video-assisted isometric strengthening exercise program significantly reduced pain and preserved muscle strength in patients recovering from lower limb fractures compared to usual care, with 33 participants in the intervention group showing notable improvements (p < .001).

The study suggests that integrating video resources into patient education can enhance the effectiveness of rehabilitation exercises, making it a practical solution for improving outcomes, especially during times of constrained healthcare resources.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Video-Assisted Isometric Strengthening Exercise Program on Pain and Muscle Strength Poststabilization of Lower Limb Fracture. Lee, WL., Ramanathan, S., Danaee, M., et al.[2023]

Isometric exercises are crucial for runners recovering from surgery as they help maintain foot and leg flexibility and rebuild muscle strength.

Performing isometric exercises multiple times a day is more effective than doing them just once, leading to better recovery outcomes for injured muscles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postsurgical management of the runner. Bonavilla, EJ.[2009]

Isometric exercise can significantly increase arterial pressure and heart rate in both normotensive individuals and hypertensive patients, primarily by increasing cardiac output without affecting peripheral vascular resistance.

Due to the potential for dangerous spikes in blood pressure during isometric exercises, it is advised that individuals with elevated blood pressure or those prone to hypertension avoid these activities to prevent serious health risks like strokes or heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemodynamic effects of isometric exercise in normotensive and hypertensive subjects. Chrysant, SG.[2017]

The Isometric Exercise Scale (IES) was found to be a valid and reliable tool for measuring perceived exertion during isometric exercises, showing a strong correlation with established measures like the Borg's CR-10 scale.

This study involving 29 male participants demonstrated that the IES can effectively monitor exercise intensity and physiological responses (like heart rate and blood pressure) during incremental isometric wall squat tests, making it a practical alternative to expensive equipment for managing exercise intensity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Validity and reliability of the 'Isometric Exercise Scale' (IES) for measuring ratings of perceived exertion during continuous isometric exercise. Lea, JWD., O'Driscoll, JM., Coleman, DA., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4478283/

Resistance Exercise Training Alters Mitochondrial Function ... 12-weeks of resistance exercise training resulted in qualitative and quantitative changes in skeletal muscle mitochondrial respiration.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5879963/

Physical activity unveils the relationship between ... Older adults who maintain a high amount of physical activity have better mitochondrial capacity, similar to highly active younger adults.

3. mdpi.com mdpi.com/1422-0067/23/20/12559

The Effects of Exercise Training on Mitochondrial Function ... We summarized the effect of exercise training on mitochondrial morphology, biogenesis, dynamics, oxidative capacity, antioxidant capacity, and quality.

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1155/2019/7058350

Stay Fit, Stay Young: Mitochondria in Movement: The Role ... Their data may suggest that intense exercise induces stronger and more rapid mitochondrial adaptation than MCIT does. However, it has been ...

5. researchgate.net researchgate.net/figure/Isometric-HIIT-increases-mitochondrial-content-and-respiratory-complexes-in_fig4_370777567

Isometric HIIT increases mitochondrial content and ... High intensity interval training (HIIT) with isometric contractions is an alternative exercise strategy in patients with DMD as HIIT is known to improve ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10015931/

An evidence-based guide to the efficacy and safety of ... IRT is efficacious and produces clinically meaningful blood pressure reductions (systolic blood pressure, 7 mmHg; diastolic blood pressure, 3 mmHg).

7. mayoclinic.org mayoclinic.org/healthy-lifestyle/fitness/expert-answers/isometric-exercises/faq-20058186

Isometric exercises: Good for strength training? Avoid holding your breath and straining during any weight training exercise. This may cause a dangerous increase in blood pressure.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5882444/

The safety of isometric exercise Few studies have investigated the relative safety of prescribing isometric exercise (IE) to reduce resting blood pressure (BP).

9. sciencedirect.com sciencedirect.com/topics/nursing-and-health-professions/isometric-exercise

Isometric Exercise - an overview In a patient with normal diastolic function, performing an isometric handgrip causes increased heart rate, blood pressure, cardiac output, and venous reversal.

10. valdperformance.com valdperformance.com/news/isometrics-static-contractions-dynamic-applications

Isometrics: Static contractions, dynamic applications Safety: Isometrics, specifically pushing isometric muscle actions (PIMAs), are often self-limiting relative to the athlete's capacity.