Exercise for Preterm Birth

Overseen By Heather L Vellers, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Texas Tech University

Disqualifiers: Bronchopulmonary hyperplasia, cardiovascular, metabolic, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Young adults born very preterm (32 weeks gestation or earlier) do not respond well to aerobic exercise training, meeting the recommendations set by the Physical Activity Guidelines for Americans, where they do not increase their fitness level (or cardiorespiratory fitness). Thus, they do not receive the health benefits of exercise. Achieving physical fitness through aerobic exercise training is the most cost-effective method for preventing and treating many diseases. Young adults born very preterm also have a higher risk of these conditions. Thus, their inability to respond to increase their fitness is a major problem. One likely explanation for poor exercise trainability and increased heart disease risk in young adults born very preterm is the effect of the early birth on the major energy producers in all our cells: Mitochondria. During late-stage gestation, mitochondria change from relying on sugar as a major fuel source to fat. Unfortunately, individuals born very preterm miss this transition in fuel source reliance, which causes significant stress and damage to mitochondria. Mitochondria are critical for post-natal organ development; thus, it is thought that preterm birth-induced mitochondrial dysfunction is the underlying cause of poor trainability and high disease risk in young adults born very preterm. Indeed, mitochondrial dysfunction is evident in these individuals. To date, there is not a way to help young adults born preterm improve their fitness level. One likely target is in the mitochondria: it's DNA. Mitochondrial DNA helps determine how mitochondria function and can be damaged under stress. Our goal in this proposed work is to determine the role of mitochondrial DNA in mitochondrial dysfunction and its link to their poor trainability. Questions: 1. Are there mitochondrial DNA markers linked to mitochondrial dysfunction and poor exercise trainability in young adults very born preterm? 2. Do mitochondrial DNA in young adults born very preterm respond differently to aerobic exercise training than those born at term? The investigators expect this work will show mitochondrial DNA changes linked to mitochondrial dysfunction and poor trainability, which can be used for future targets to improve health. This work supports AHA mission by helping to identify a marker in individuals born very preterm linked to their higher heart disease risk and death early in life.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is exercise generally safe for humans?

Research shows that exercise, including resistance training, is generally safe for adults and can improve health outcomes like reducing mortality and cardiovascular disease. Serious adverse events are not common, although they are not always consistently reported in studies. ^{1 2 3 4 5}

How does exercise as a treatment for preterm birth differ from other treatments?

Exercise for preterm birth is unique because it focuses on physical activity to potentially improve outcomes, unlike other treatments that might involve medication or medical procedures. This approach is non-invasive and leverages the body's natural ability to adapt and strengthen through regular movement. ^{6 7 8 9 10}

What data supports the effectiveness of the treatment Exercise, Physical Activity, Workout, Fitness Training for Preterm Birth?

Research shows that exercise can be beneficial in various medical settings, such as helping arthritis patients improve after hospital discharge and supporting recovery in critically ill patients. This suggests that exercise might also help improve outcomes for preterm birth, although direct evidence is not provided. ^{11 12 13 14 15}

Are You a Good Fit for This Trial?

This trial is for inactive young adults aged 18-35 who were born preterm (before 37 weeks) and their biological mothers, as well as age- and sex-matched controls born at term. Participants must exercise less than 150 minutes per week and pass a health readiness assessment to start moderate-intensity exercise.

Inclusion Criteria

I am cleared to start a moderate-intensity exercise program based on the PAR-Q+ assessment.

I am the biological mother who gave birth to the participant.

I was born before 37 weeks of pregnancy, am 18-35 years old, and exercise less than 150 minutes a week.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Mitochondrial DNA Sequencing

Participants provide a blood or saliva sample for mitochondrial DNA sequencing analysis to assess for variants unique to individuals born prematurely

1 visit

1 visit (in-person)

Aerobic Exercise Training

Participants complete a 16-week aerobic exercise training program

16 weeks

Regular visits for exercise sessions

Follow-up

Participants are monitored for changes in mitochondrial oxidative capacity and maximal aerobic capacity after the training program

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Exercise

Trial Overview The study investigates if mitochondrial DNA markers are linked to poor aerobic exercise response in young adults born very preterm. It aims to understand how mitochondrial DNA affects fitness trainability by comparing responses of these individuals with those born at term.

How Is the Trial Designed?

Group I: Aerobic Exercise Training Experimental Treatment 1 Intervention

Participants will be asked to complete a 16-week aerobic exercise training program.

Group II: Mitochondrial DNA Sequencing Active Control 1 Intervention

Participants will be asked to provide a blood or saliva sample for mitochondrial DNA sequencing analysis to assess for variants unique to individuals born prematurely.

Who Is Running the Clinical Trial?

Texas Tech University

Lead Sponsor

Trials

89

Recruited

10,300+

Published Research Related to This Trial

Early upper-limb exercise training combined with general physiotherapy significantly improves exercise capacity in patients recovering from acute respiratory failure after mechanical ventilation, as shown by better performance in both incremental and endurance tests.

The study indicates that early exercise training is feasible and beneficial in respiratory intermediate ICUs, with improvements in muscle fatigue and dyspnea, particularly in patients with better baseline inspiratory muscle function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supported arm training in patients recently weaned from mechanical ventilation. Porta, R., Vitacca, M., Gilè, LS., et al.[2022]

In a study of 91 mechanically ventilated patients, exercise rehabilitation was found to be safe, with only 10 minor adverse events (0.0182%) reported, indicating a low risk associated with this intervention.

The results support the consensus recommendations for exercise rehabilitation in intensive care, suggesting that even patients on moderate vasoactive support can safely begin rehabilitation, highlighting the potential for broader application of these guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

When is it safe to exercise mechanically ventilated patients in the intensive care unit? An evaluation of consensus recommendations in a cardiothoracic setting. Boyd, J., Paratz, J., Tronstad, O., et al.[2018]

In a pilot study involving 12 critically ill children in a Pediatric Critical Care Unit, virtual reality exercise using Nintendo Wii™ Boxing was found to be safe, with no adverse events reported during the intervention.

While the VR exercise increased upper limb activity compared to daily activity, challenges in feasibility were noted, as only 8 participants completed the study, indicating potential barriers to implementation in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"Wii-Hab" in critically ill children: a pilot trial. Abdulsatar, F., Walker, RG., Timmons, BW., et al.[2022]

Short-term intensive exercise training (IET) following hospital discharge significantly improves function in patients with rheumatoid arthritis or osteoarthritis, with benefits observed in range of motion and disability measures up to 52 weeks after the intervention.

The IET group showed faster improvements compared to usual care, particularly in disability scores, with a significant mean difference of -5.5 in the McMaster Toronto Arthritis Patient Preference Disability Questionnaire at 3 weeks, indicating a clinically relevant impact on patient function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Arthritis patients show long-term benefits from 3 weeks intensive exercise training directly following hospital discharge. Bulthuis, Y., Drossaers-Bakker, KW., Taal, E., et al.[2022]

Patients recovering from critical illness engaged in very limited physical activity, spending less than 5% of their day active during their hospital stay, despite rehabilitation efforts.

Physical activity significantly increased from the ICU to the ward, with an average increase of 35 minutes per day, highlighting the importance of early rehabilitation to enhance recovery outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical activity of patients with critical illness undergoing rehabilitation in intensive care and on the acute ward: An observational cohort study. Rollinson, TC., Connolly, B., Berlowitz, DJ., et al.[2022]

A study involving 90 patients with severe respiratory failure showed that implementing an early exercise safety management program during mechanical ventilation significantly improved mental health, lung function, and overall quality of life compared to standard care.

The early exercise program also resulted in a lower incidence of complications (24.44% vs. 57.78%), highlighting its safety and effectiveness in the ICU setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Application of early exercise safety management in patients undergoing mechanical ventilation in intensive care unit]. Zhang, L., Yan, R., Zhou, Y., et al.[2020]

Resistance training (RT) significantly reduces all-cause mortality and the incidence of cardiovascular disease while improving physical functioning in adults, based on an analysis of 11 systematic reviews involving over 382,000 participants.

Although adverse events were not consistently reported, serious adverse events related to RT were uncommon, suggesting that the benefits of resistance training outweigh the potential harms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resistance training and health in adults: an overview of systematic reviews. El-Kotob, R., Ponzano, M., Chaput, JP., et al.[2021]

The study demonstrated that the Rating of Perceived Exertion (RPE) is a valid and reliable measure for assessing the intensity of isometric wall squats, effectively correlating with physiological responses like heart rate and blood pressure.

RPE can distinguish between different knee angles during wall squats with a precision of 10 degrees, making it a useful tool for patients and practitioners to monitor exercise intensity and its effects on blood pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Validity and reliability of RPE as a measure of intensity during isometric wall squat exercise. Lea, JWD., O'Driscoll, JM., Coleman, DA., et al.[2022]

The SPRINT protocol, which combines aerobic and resistive training using a flywheel device, was tested in a pilot study with five healthy male subjects over 2 weeks, showing that while physiological effects were similar, the addition of a VR simulation improved motivation, mood, and overall well-being during exercise.

The study suggests that incorporating a VR 'exergaming' simulation with real-time biometric feedback could enhance the psychological benefits of exercise, making it a valuable tool for astronauts facing isolation during long-duration space missions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Virtual Reality "exergames": A promising countermeasure to improve motivation and restorative effects during long duration spaceflight missions. Keller, N., Whittle, RS., McHenry, N., et al.[2022]

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]

A study involving 24 children with spastic diplegic cerebral palsy and 12 without neurological impairments found that performing maximum effort exercises did not increase muscle spasticity, as measured by the pendulum test.

The results challenge the traditional belief that resistive exercise exacerbates spasticity in individuals with cerebral palsy, suggesting that such exercises may be safe and not detrimental to muscle function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of quadriceps femoris muscle strengthening exercises on spasticity in children with cerebral palsy. Fowler, EG., Ho, TW., Nwigwe, AI., et al.[2009]

In a study involving 6 adults with spastic quadriplegia, passive range of motion (PROM) exercises did not show a significant effect on joint flexibility, as measured by goniometric assessments.

The research utilized a single-subject design, revealing that there was no difference in lower-extremity measurements between phases with and without PROM exercises, suggesting that these exercises may not be effective for improving joint range in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of passive range of motion exercises on lower-extremity goniometric measurements of adults with cerebral palsy: a single-subject design. Cadenhead, SL., McEwen, IR., Thompson, DM.[2011]

Whole body vibration training (WBVT) significantly improved the 6 Minute Walking Distance (6MWD) by an average of 35 meters in COPD patients after 12 weeks, indicating its efficacy as a rehabilitation method.

Both WBVT and resistance training (RT) showed similar improvements in exercise capacity and quality of life, but only 30% of patients in the WBVT group reached the minimally clinically important difference (MCID) for 6MWD, suggesting that while effective, WBVT may not be as impactful as RT in achieving significant clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Whole Body Vibration in Patients With COPD. Salhi, B., Malfait, TJ., Van Maele, G., et al.[2022]

An 8-week study involving 24 children with spastic cerebral palsy found that neither proprioceptive neuromuscular facilitation stretching nor static stretching led to significant improvements in muscle-tendon properties, muscle strength, or ankle joint function.

Both stretching techniques showed high adherence rates (over 93%), but ultimately, the study suggests that manual stretching alone may not be effective for enhancing physical function in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eight weeks of proprioceptive neuromuscular facilitation stretching and static stretching do not affect muscle-tendon properties, muscle strength, and joint function in children with spastic cerebral palsy. Kruse, A., Habersack, A., Weide, G., et al.[2023]

In a study of 38 children with unilateral cerebral palsy, those who participated in 24 sessions of plyometric exercise over 3 months showed significant improvements in the structure and function of their plantar flexor muscles compared to a control group that received traditional therapy.

Plyometric exercise led to notable changes in muscle and tendon characteristics, such as increased muscle thickness and tendon length, which could enhance muscular efficiency and overall physical performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanical and Morphological Changes of the Plantar Flexor Musculotendinous Unit in Children with Unilateral Cerebral Palsy Following 12 Weeks of Plyometric Exercise: A Randomized Controlled Trial. Elnaggar, RK., Alghamdi, MS., Alenazi, AM., et al.[2022]

Citations

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

Supported arm training in patients recently weaned from mechanical ventilation. [2022]

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

When is it safe to exercise mechanically ventilated patients in the intensive care unit? An evaluation of consensus recommendations in a cardiothoracic setting. [2018]

3. Netherlands pubmed.ncbi.nlm.nih.gov

"Wii-Hab" in critically ill children: a pilot trial. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Arthritis patients show long-term benefits from 3 weeks intensive exercise training directly following hospital discharge. [2022]

5. Australia pubmed.ncbi.nlm.nih.gov

Physical activity of patients with critical illness undergoing rehabilitation in intensive care and on the acute ward: An observational cohort study. [2022]

6. China pubmed.ncbi.nlm.nih.gov

[Application of early exercise safety management in patients undergoing mechanical ventilation in intensive care unit]. [2020]

7. Canada pubmed.ncbi.nlm.nih.gov

Resistance training and health in adults: an overview of systematic reviews. [2021]

8. Singapore pubmed.ncbi.nlm.nih.gov

Validity and reliability of RPE as a measure of intensity during isometric wall squat exercise. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Virtual Reality "exergames": A promising countermeasure to improve motivation and restorative effects during long duration spaceflight missions. [2022]

10. 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]

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

The effect of quadriceps femoris muscle strengthening exercises on spasticity in children with cerebral palsy. [2009]

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

Effect of passive range of motion exercises on lower-extremity goniometric measurements of adults with cerebral palsy: a single-subject design. [2011]

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

Effects of Whole Body Vibration in Patients With COPD. [2022]

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

Eight weeks of proprioceptive neuromuscular facilitation stretching and static stretching do not affect muscle-tendon properties, muscle strength, and joint function in children with spastic cerebral palsy. [2023]

15. Switzerland pubmed.ncbi.nlm.nih.gov

Mechanical and Morphological Changes of the Plantar Flexor Musculotendinous Unit in Children with Unilateral Cerebral Palsy Following 12 Weeks of Plyometric Exercise: A Randomized Controlled Trial. [2022]