Exercise Program for Pediatric Pulmonary Hypertension

(iTONE Trial)

Overseen By Catherine Avitabile, MD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Children's Hospital of Philadelphia

Disqualifiers: Functional class III/IV, Single ventricle, Renal disease, Hepatic impairment, 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: Unknown

Duration: 16 weeks

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to determine if a home exercise program can improve physical activity and quality of life for children and teens with pulmonary hypertension (high blood pressure in the lungs). Participants will follow a 16-week exercise plan, combining aerobic activities like walking or biking with resistance exercises. A smartwatch and heart rate monitor will track progress. This trial suits children and teens aged 8-18 who have been diagnosed with pulmonary hypertension, can walk, and have stable medication routines. As an unphased trial, it offers participants the opportunity to contribute to valuable research that could enhance future treatment options.

Will I have to stop taking my current medications?

The trial requires that participants have a stable PH medication regimen for 3 months before starting, so you should not stop taking your current medications.

What prior data suggests that this exercise intervention is safe for children with pulmonary hypertension?

Research shows that exercise is a safe and effective way to help adults with pulmonary hypertension (PH), which is high blood pressure in the lungs. However, less information exists about exercise's effects on children with PH, and exercise has not been commonly used to treat them. Reports of safety problems are rare, and children generally handle exercise well in many situations.

This trial examines a home exercise program for children and teenagers with PH. The program includes activities like walking, biking, or light jogging, along with some light strength exercises. Participants will use a smartwatch and heart rate monitor to track their activity. The exercise level is carefully controlled, with a maximum heart rate set to ensure safety. This approach aims to increase physical activity while keeping participants safe and comfortable. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this exercise program for pediatric pulmonary hypertension because it offers a non-pharmacological approach to managing the condition. Unlike standard treatments that often involve medications like endothelin receptor antagonists or phosphodiesterase-5 inhibitors, this program uses personalized aerobic and resistance exercises that can be done at home, making it more accessible and sustainable for families. The program also incorporates modern technology, such as smartwatches and heart rate monitors, to provide real-time feedback and support, potentially increasing adherence and effectiveness. This innovative approach could improve quality of life and physical fitness for children with pulmonary hypertension without the side effects associated with medication.

What evidence suggests that this exercise intervention is effective for pediatric pulmonary hypertension?

Research shows that exercise is a promising way to manage pulmonary hypertension (PH) in adults without medication. Although less is known about its effects on children, studies have found that kids with PH are usually much less active than their healthy peers. This lack of activity links to reduced muscle mass and poorer performance in physical activities. Studies in adults demonstrate that exercise can improve heart health and quality of life. This trial will test a personalized home exercise intervention for children with PH, aiming to increase their activity levels and overall well-being. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

The iTONE Trial is for children and teenagers aged 8-18 with pulmonary hypertension (PH), who can walk, have an oxygen saturation over 85% during a walking test, and are in the early stages of their condition. They should not have severe PH and must be on stable medication for at least three months.

Inclusion Criteria

I can walk on my own.

My pulmonary hypertension medication has been the same for the last 3 months.

Home Wifi connection

Exclusion Criteria

Current pregnancy

Single ventricle physiology

Significant developmental delay/inability to comply with verbal instructions to complete the study procedures

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Baseline assessment of muscle mass and strength, 6-minute walk test distance, and quality of life

1 week

Treatment

16-week home exercise program with wearable activity monitoring and periodic text messages to promote adherence

16 weeks

Remote monitoring with periodic data transmission

Post-intervention Assessment

Assessment of muscle mass and strength, 6-minute walk test distance, and quality of life after the intervention

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Exercise intervention

Trial Overview

This study tests a 16-week exercise program using wearable activity monitors to increase physical activity and muscle mass, which may improve exercise performance and quality of life in young patients with PH.

How Is the Trial Designed?

Group I: Home exercise intervention Experimental Treatment 1 Intervention

* Personalized 16 week home exercise program - aerobic exercise for 20 minutes per day/4 days per week and light resistance exercise using resistance bands 3 days per week. * Aerobic sessions will include walking, biking, or light jogging, depending on access to facilities/equipment and weather. * Smartwatch for the length of the intervention and a heart rate monitor during exercise sessions. * Max heart rate prescribed will be 80% of that on recent cardiopulmonary exercise test (at most 150 beats/min). * Heart rate monitor will sync with the smartwatch. * Activity and heart rate data will be transmitted to the study team via a data hub connected to the participant's home internet modem several times per week. * Periodic text messaging to remind participants to wear the watch, sync the data, or adhere to heart rate goals, to ask about symptoms, or to support activity progress. * Multiple ways to contact the study team with questions or concerns.

Who Is Running the Clinical Trial?

Children's Hospital of Philadelphia

Lead Sponsor

Trials

749

Recruited

11,400,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

A specialized exercise training and rehabilitation program is recommended as an effective add-on treatment for patients with pulmonary arterial hypertension, showing significant improvements in symptoms, exercise capacity, and quality of life across over 470 patients in various studies.

The safety profile of these exercise programs is acceptable, with some studies indicating excellent survival rates over 1 to 2 years, although most studies had small sample sizes and were not designed to measure long-term clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Principles of rehabilitation and reactivation: pulmonary hypertension. Marra, AM., Egenlauf, B., Bossone, E., et al.[2015]

Historically, exercise training was not recommended for patients with pulmonary hypertension due to concerns about safety and potential drops in cardiac output during exertion.

Recent evidence suggests that exercise training is safe and effective for improving exercise capacity, peak oxygen consumption, and quality of life in pulmonary hypertension patients, indicating it should be included as part of their treatment plan alongside optimal medical therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary hypertension and exercise training: a synopsis on the more recent evidences. Leggio, M., Fusco, A., Armeni, M., et al.[2019]

Regular exercise training has been shown to be safe and effective in improving quality of life and cardiorespiratory fitness in patients with pulmonary arterial hypertension (PAH), despite the limited number of studies available.

Emerging evidence suggests that specific training recommendations can be developed to enhance rehabilitation programs for PAH patients, addressing their unique physiological challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of Exercise Interventions in Pulmonary Arterial Hypertension and Recommendations for Rehabilitation Programing. Ozemek, C., Berry, MJ., Arena, R.[2020]

A 12-week text message-based intervention significantly increased daily step counts in patients with pulmonary arterial hypertension (PAH), with an average increase of 1,409 steps compared to a decrease of 149 steps in the control group.

The intervention also led to improvements in quality of life and reductions in visceral fat, suggesting that mobile health strategies can effectively promote physical activity in PAH patients, although no significant change was observed in the six-minute walk test.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Mobile Health Intervention to Increase Physical Activity in Pulmonary Arterial Hypertension. Hemnes, AR., Silverman-Lloyd, LG., Huang, S., et al.[2022]

A study involving 8 congenital heart disease patients with pulmonary hypertension showed that a 3-month directed exercise rehabilitation program was safe and did not lead to any adverse events, such as worsening symptoms or heart failure.

Patients who participated in the rehabilitation program demonstrated improvements in their 6-minute walk test and functional class, indicating that structured exercise can be beneficial for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rehabilitation program in adult congenital heart disease patients with pulmonary hypertension. Martínez-Quintana, E., Miranda-Calderín, G., Ugarte-Lopetegui, A., et al.[2022]

This randomized controlled trial will assess the effects of an 8-week exercise program on muscle power and mass in patients with pulmonary artery hypertension (PAH), involving at least 48 participants.

The study aims to evaluate various health outcomes, including exercise capacity and quality of life, which will help understand the benefits of exercise in managing PAH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and Design of a Randomized Controlled Trial Evaluating Whole Muscle Exercise Training Effects in Outpatients with Pulmonary Arterial Hypertension (WHOLEi+12). Sanchis-Gomar, F., González-Saiz, L., Sanz-Ayan, P., et al.[2022]

A 4-week cardiorespiratory training program for 15 patients with pulmonary arterial hypertension (PAH) significantly improved their exercise capacity, as shown by an 8% increase in the 6-minute walk test distance and a 22% increase in workload during cardiopulmonary exercise testing.

The training program also enhanced the patients' quality of life, with significant reductions in anxiety and depression scores, and no adverse events were reported, indicating the program's safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of an Outpatient Service Rehabilitation Programme in Patients Affected by Pulmonary Arterial Hypertension: An Observational Study. Bussotti, M., Gremigni, P., Pedretti, RFE., et al.[2022]

A 12-week pilot study involving 16 patients with pulmonary arterial hypertension (PAH) showed that outpatient exercise programs, including multidisciplinary rehabilitation and home walking, may improve hemodynamic function and quality of life.

The study found improvements in right ventricular function, pulmonary artery pressure, and muscle strength, indicating that exercise is feasible and safe for PAH patients, but further research is needed to confirm these benefits due to the small sample size.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The exercise in pulmonary arterial hypertension (ExPAH) study: A randomized controlled pilot of exercise training and multidisciplinary rehabilitation in pulmonary arterial hypertension. Chia, KSW., Shiner, CT., Brown, K., et al.[2022]

A retrospective analysis of 18 patients with pulmonary hypertension (PHTN) showed significant improvements in treadmill speed after a 12-week pulmonary rehabilitation program, with speeds increasing from 1.3 mph to 2.2 mph (P<0.0001).

Overall, 88.9% of participants experienced improvements in exercise capacity, highlighting the effectiveness of structured pulmonary rehabilitation as a key component in managing PHTN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise tolerance improves after pulmonary rehabilitation in pulmonary hypertension patients. Talwar, A., Sahni, S., Verma, S., et al.[2020]

A 16-week home exercise training program was feasible and well-tolerated in 9 children and adolescents with low-risk pulmonary arterial hypertension (PAH), with no adverse events reported.

Participants showed significant improvements in exercise capacity, including increased treadmill running distance and oxygen consumption at the anaerobic threshold, suggesting that home-based training can be beneficial for young patients with PAH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Home Exercise Training in Children and Adolescents with Pulmonary Arterial Hypertension: A Pilot Study. Zöller, D., Siaplaouras, J., Apitz, A., et al.[2018]

In a study of 30 patients with severe pulmonary hypertension, a 15-week program of exercise and respiratory training significantly improved walking distance by an average of 111 meters compared to a control group, indicating enhanced physical capacity.

The training also led to improvements in quality of life and other health metrics, suggesting that exercise and respiratory training can be a beneficial addition to standard medical treatments for pulmonary hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise and respiratory training improve exercise capacity and quality of life in patients with severe chronic pulmonary hypertension. Mereles, D., Ehlken, N., Kreuscher, S., et al.[2023]

Cardiopulmonary stress testing is safe for children with pulmonary arterial hypertension, providing valuable clinical insights into their condition.

Children with pulmonary hypertension showed significantly lower aerobic capacity compared to healthy controls, with peak oxygen consumption levels indicating a strong correlation with disease severity measures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utility of cardiopulmonary stress testing in assessing disease severity in children with pulmonary arterial hypertension. Yetman, AT., Taylor, AL., Doran, A., et al.[2016]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39421015/

Barriers to and facilitators of physical activity in pediatric ...

Therapeutic exercise has not been widely adopted in pediatric pulmonary hypertension (PH), despite adult data supporting its safety and efficacy ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06549452

Mobile Health Intervention to Improve Exercise in Pediatric ...

Children and adults with pulmonary arterial hypertension (PAH) have severely reduced daily activity compared to healthy populations.

3.

onlinelibrary.wiley.com

onlinelibrary.wiley.com/doi/full/10.1002/pul2.70000

Barriers to and facilitators of physical activity in pediatric ...

Therapeutic exercise has not been widely adopted in pediatric pulmonary hypertension (PH), despite adult data supporting its safety and efficacy

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11219287/

Creating a digital approach for promoting physical activity ...

Data support exercise as an effective nonpharmacologic intervention among adults with PH. However, data on exercise training in children and ...

5.

atsjournals.org

atsjournals.org/doi/full/10.1164/rccm.201608-1576OC

Physical Activity in Pediatric Pulmonary Arterial ...

This study shows that physical activity measured by accelerometry is markedly decreased in children with PAH compared with in healthy control patients.