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

Trial Summary

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 data supports the effectiveness of the treatment Exercise Program for Pediatric Pulmonary Hypertension?

Research shows that exercise programs can improve symptoms, exercise capacity, and quality of life in patients with pulmonary hypertension. Studies have found that supervised exercise training is safe and can lead to better heart function and reduced symptoms in these patients. ^{1 2 3 4 5}

Is exercise safe for people with pulmonary hypertension?

Exercise programs for people with pulmonary hypertension have been shown to be generally safe when supervised by experienced centers. Studies report improvements in symptoms and quality of life, with an acceptable safety profile, although most studies involved small groups and were not designed to assess long-term outcomes. ^{4 5 6 7 8}

How does the exercise treatment for pediatric pulmonary hypertension differ from other treatments?

The exercise treatment for pediatric pulmonary hypertension is unique because it focuses on improving exercise capacity and quality of life through physical activity, rather than relying solely on medication. This approach is novel as exercise training was historically not recommended for pulmonary hypertension, but recent studies have shown its safety and efficacy in enhancing functional outcomes and cardiorespiratory fitness. ^{2 9 10 11 12}

What is the purpose of this trial?

Children with pulmonary hypertension (PH) engage in less physical activity than their peers. This is a concern since adult data support exercise as a non-pharmacologic treatment for PH. Despite adult data, therapeutic exercise has not been widely adopted in pediatric PH. Investigators have previously demonstrated that children with PH have less skeletal muscle mass in association with worse exercise performance. Interventions to increase physical activity and skeletal muscle mass may improve exercise performance and quality of life in children with PH. This study will use wearable activity monitoring devices to promote physical activity in a 16-week pilot intervention in children and teenager with PH.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

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]

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 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]

References

1. United States 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. [2022]

2. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Effects of an Outpatient Service Rehabilitation Programme in Patients Affected by Pulmonary Arterial Hypertension: An Observational Study. [2022]

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

Exercise and respiratory training improve exercise capacity and quality of life in patients with severe chronic pulmonary hypertension. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Principles of rehabilitation and reactivation: pulmonary hypertension. [2015]

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

A Mobile Health Intervention to Increase Physical Activity in Pulmonary Arterial Hypertension. [2022]

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

Rehabilitation program in adult congenital heart disease patients with pulmonary hypertension. [2022]

7. United States 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). [2022]

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

Utility of cardiopulmonary stress testing in assessing disease severity in children with pulmonary arterial hypertension. [2016]

9. Korea (South) pubmed.ncbi.nlm.nih.gov

Exercise tolerance improves after pulmonary rehabilitation in pulmonary hypertension patients. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Pulmonary hypertension and exercise training: a synopsis on the more recent evidences. [2019]

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

A Review of Exercise Interventions in Pulmonary Arterial Hypertension and Recommendations for Rehabilitation Programing. [2020]

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

Home Exercise Training in Children and Adolescents with Pulmonary Arterial Hypertension: A Pilot Study. [2018]