Exercise Training for Pulmonary Arterial Hypertension

Overseen By Yogesh Reddy

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Mayo Clinic

Disqualifiers: Heart failure, Anemia, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine how different types of exercise can help individuals with Pulmonary Arterial Hypertension (PAH) feel better and improve their quality of life. Researchers compare whole-body aerobic exercises, such as walking or cycling, with leg-focused strength exercises using weights. Individuals experiencing PAH symptoms who have not been recently hospitalized for heart failure might be suitable for this study. The trial also includes healthy participants to facilitate result comparisons. As an unphased trial, it offers participants the chance to contribute to valuable research that could enhance exercise recommendations for PAH patients.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that participants should not have started a new pulmonary vasodilator in the last 60 days.

What prior data suggests that these exercise training methods are safe for patients with Pulmonary Arterial Hypertension?

Research shows that exercise is generally safe for people with pulmonary arterial hypertension (PAH). Studies have found that aerobic exercise can enhance exercise capacity, improve heart and lung function, and boost overall quality of life, all without serious side effects.

For leg-focused exercises, research indicates similar safety and benefits. These exercises can also enhance exercise capacity and overall fitness. However, careful monitoring of exercise programs is crucial, as not all risks can be completely avoided.

Overall, both aerobic and leg exercises appear safe and beneficial for people with PAH. However, healthcare professionals should supervise any exercise program to ensure safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores exercise as a potential game-changer for people with Pulmonary Arterial Hypertension (PAH). Traditionally, PAH is managed with medications like endothelin receptor antagonists and phosphodiesterase-5 inhibitors that target blood vessels. In contrast, this trial looks at how aerobic and leg training exercises could improve heart and lung function, offering a non-drug approach. These exercises might enhance physical endurance and quality of life without the side effects typical of medications. If successful, it could pave the way for exercise-based interventions as a valuable addition to current PAH treatment strategies.

What evidence suggests that this trial's treatments could be effective for Pulmonary Arterial Hypertension?

Research shows that exercise can significantly enhance exercise capacity, heart and lung health, and overall quality of life for people with pulmonary hypertension (high blood pressure in the lungs). In this trial, participants will be randomized to different exercise regimens. Studies have found that aerobic exercise, which participants in one arm of this trial will undergo, can boost physical activity levels and improve heart function, crucial for individuals with this condition. Similarly, leg exercises, which participants in another arm will perform, have been linked to better exercise ability, including improvements in walking distance and peak power. Both types of exercise are generally safe and can help reduce symptoms like shortness of breath. Overall, these findings suggest that exercise could effectively manage symptoms of pulmonary arterial hypertension. ^{1 2 4 5 6}

Who Is on the Research Team?

Yogesh Reddy, M.B.B.S

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for adults with Pulmonary Arterial Hypertension (PAH) who are stable, not hospitalized recently, and haven't started new PAH drugs in the last 60 days. Healthy individuals without heart failure can also join as controls. Exclusions include recent severe cardiovascular events, inability to exercise, need for oxygen supplementation, pregnancy or potential pregnancy without effective contraception.

Inclusion Criteria

Criterion Summary: For patients with Pulmonary Arterial Hypertension (PAH): - You have given consent to participate in the trial. - You are in NYHA Class II-IV. - Your Left Ventricular Ejection Fraction (LVEF) is equal to or greater than 40% in the past year. - You have not been hospitalized due to heart failure in the last 30 days. - You have not started a new pulmonary vasodilator in the last 60 days. - Your mean Pulmonary Arterial (PA) pressure is equal to or greater than 20 mmHg with Pulmonary Vascular Resistance (PVR) greater than 2 Wood units, as determined by right heart catheterization. - Your exercise Pulmonary Capillary Wedge Pressure (PCWP) is less than 25 mm Hg. - You are symptomatic with PAH and planning to undergo exercise right heart catheterization for reassessment of exertional symptoms. For healthy controls: - You have given consent to participate in the trial. - You do not have a known diagnosis of heart failure.

Exclusion Criteria

You have experienced a heart attack, stroke, or heart-related hospitalization in the last 30 days, or you have certain heart conditions that could cause difficulty in breathing or exercising. You are unable to walk without assistance, have chronic low oxygen levels, have certain muscle or bone conditions, or have been involved in certain medical trials recently. You are pregnant, breastfeeding, or planning to become pregnant, or you have a severe psychiatric disorder, have had recent suicidal behavior, or are suspected of drug abuse.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants complete baseline study assessments before randomization

1 week

Treatment

Participants undergo either aerobic training or leg training for 12 weeks

12 weeks

Follow-up

Participants are monitored for changes in skeletal muscle O2 diffusive conductance and quality of life

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Aerobic Training
• Leg Training

Trial Overview The study compares two types of physical training: whole body aerobic exercises versus targeted leg strength training. It aims to determine which method better improves symptoms and life quality in PAH patients.

How Is the Trial Designed?

Group I: Leg Training Experimental Treatment 1 Intervention

Subjects with PAH will be enrolled to complete baseline study assessments, be randomized to undergo leg training for 12 weeks, and then repeat study assessments.

Group II: Aerobic Training Active Control 1 Intervention

Subjects with PAH will be enrolled to complete baseline study assessments, be randomized to undergo aerobic training for 12 weeks, and then repeat study assessments.

Group III: Healthy Controls Active Control 1 Intervention

Healthy controls will be enrolled to complete the baseline study assessments for generation of normal reference values for comparison. Healthy controls will not undergo randomized exercise training interventions or repeat assessments.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In a study of 25 females with pulmonary hypertension undergoing a 10-week aerobic exercise training program, significant improvements in cardiorespiratory function were observed in those with high (HI) and low (LI) increases in 6-minute walk test distance, but not in those with negative (NEG) adaptations.

The HI group showed notable enhancements in ventilatory efficiency and other key respiratory metrics post-training, suggesting that some patients may struggle with exercise adaptation due to sustained ventilatory inefficiency, which could limit their exercise capacity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiopulmonary exercise test indices of respiratory buffering before and after aerobic exercise training in women with pulmonary hypertension: Differentiation by magnitudes of change in six-minute walk test performance. Morris, ZV., Chin, LMK., Chan, L., et al.[2023]

In a study of 18 women with pulmonary arterial hypertension (PAH) undergoing 10 weeks of vigorous aerobic exercise training, significant improvements were observed in cardiac function, including a decrease in systemic vascular resistance at peak exercise, suggesting enhanced heart efficiency.

The study found that vigorous aerobic exercise did not lead to declines in left ventricular function, indicating that such training may be safe and beneficial for women with PAH by potentially reducing afterload and preserving diastolic function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left Ventricular Function Before and After Aerobic Exercise Training in Women With Pulmonary Arterial Hypertension. Woolstenhulme, JG., Guccione, AA., Herrick, JE., et al.[2023]

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 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 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]

Aerobic exercise training is beneficial for patients with pulmonary arterial hypertension as it helps improve skeletal muscle function and exercise tolerance, addressing issues like muscle myopathy and atrophy.

The review discusses how aerobic exercise leads to positive changes in muscle through mechanisms such as reduced inflammation, enhanced anabolic processes, and better mitochondrial function, although the exact pathways are still being explored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Skeletal muscle dysfunctions in pulmonary arterial hypertension: Effects of aerobic exercise training. Drummond, FR., Leite, LB., de Miranda, DC., et al.[2023]

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]

A 6-week outpatient exercise training program significantly improved exercise tolerance and health-related quality of life in two individuals with pulmonary arterial hypertension (PAH), with no adverse effects reported.

Both subjects showed notable increases in oxygen consumption and distance walked in the six-minute walk test, indicating enhanced aerobic capacity and overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise training in patients with pulmonary arterial hypertension: a case report. Shoemaker, MJ., Wilt, JL., Dasgupta, R., et al.[2021]

An 8-month exercise intervention in patients with pulmonary arterial hypertension (PH) showed improvements in physical capacity, NT-proBNP levels, physical activity, and quality of life, indicating the potential benefits of exercise in managing this condition.

The study provides detailed pre and post-intervention data categorized by New York Heart Association (NYHA) class, enhancing our understanding of how exercise impacts different severity levels of PH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of an 8-month exercise intervention on physical capacity, NT-proBNP, physical activity levels and quality of life data in patients with pulmonary arterial hypertension by NYHA class. Santos-Lozano, A., Sanz-Ayan, P., González-Saiz, L., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7330286/

Effectiveness and safety of exercise training ... Exercise training is associated with a significant improvement in exercise capacity, cardiorespiratory fitness and quality of life among patients with PH

2. sciencedirect.com sciencedirect.com/science/article/pii/S2666668525000011

Physical exercise for pulmonary arterial hypertension ... Though several studies have reported an improved QoL and exercise capacity, and reduced breathlessness symptoms in PH patients after inspiratory muscle training ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00678821

Aerobic Exercise in Patients With Pulmonary Hypertension This study will determine if a rehabilitation exercise program can help people with pulmonary hypertension (PH) increase their physical activity.

4. frontiersin.org frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.835272/full

A Study of the Efficacy and Safety of Aerobic Exercise ... Recent data suggest that the cardiac index during exercise may independently predict the survival of PAH patients (28). Improved RV function and ...

5. ahajournals.org ahajournals.org/doi/10.1161/circheartfailure.115.002130

Efficacy and Safety of Exercise Training in Chronic ... Conclusions— Exercise training in patients with pulmonary hypertension appears safe and is associated with a significant improvement in exercise capacity, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9016180/

A Study of the Efficacy and Safety of Aerobic Exercise Training ... Patients with pulmonary arterial hypertension (PAH) have reduced exercise capacity and poor quality of life. Exercise-based rehabilitation ...