Clinical Trial: The Effect of Adding Exercise Training to Optimal Therapy in PAH
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: The Effect of Adding Exercise Training to Optimal Therapy in Pulmonary Arterial Hypertension
Brief Summary:
Exercise capacity (EC) is limited in pulmonary arterial hypertension (PAH) by impaired right ventricular (RV) function and inability to increase stroke volume (SV). Disease targeted therapy, increases EC by improving SV. Additional factors may contribute to exercise limitation:
- Peripheral and respiratory muscle dysfunction
- Autonomic dysfunction
- An altered profile of inflammation
- Mitochondrial dysfunction.
The enhancement of EC achieved pharmacologically may therefore be limited. Exercise training in PAH improves EC and quality of life (QOL). The changes in physiology responsible for this improvement are not clear. Patients with PAH stable on optimal oral therapy, but not meeting treatment goals, will be enrolled in a 30-week randomised exercise training program.
One arm will undertake training for 15 weeks (3 weeks residential, 12 outpatient), the other will receive standard care for 15 weeks then 15 weeks training.
Aims:
- Demonstrate that exercise training can enhance EC and QOL when added to optimal drug therapy a UK PAH population.
-
Explore mechanisms of exercise limitation and factors that improve with training, assessing:
- Cardiac function
- Skeletal muscle function
- Autonomic function
- Respiratory muscle strength
- Pulmonary arterial hypertension (PAH) is characterised by increased pulmonary vascular resistance (PVR) and elevation of pulmonary artery pressure (PAP) at rest, which rises markedly on exercise. Traditionally, exercise limitation had been attributed to impaired right ventricular (RV) function and an inability of the heart to increase stroke volume (SV) in response to exercise. Disease targeted therapy improves SV by reducing PVR and therefore afterload, with combination therapy being superior in this regard. Despite advances in medical therapy, most patients remain symptomatic on treatment. The 2014 UK PAH national audit demonstrates a 65% failure rate of monotherapy at 2 years. This lack of improvement in exercise tolerance suggests additional mechanisms other than poor SV are responsible for exercise limitation. There is consequently a need for new treatment strategies to improve morbidity and mortality in PAH.
Over the past decade, it has been demonstrated that exercise training in PAH can improve exercise capacity and quality of life (QOL). Exercise training has been shown to result in more significant improvements in exercise capacity and QOL than the majority of pharmacological therapies, with reassuring safety and health economics. Currently, exercise therapy is not part of standard care in the UK and many other European countries. There are several unanswered questions that pose a barrier to its widespread implementation; these fall into three main domains:
A. Relationship with drug therapy
The standard of PAH care is moving towards combination therapy. In the previous studies assessing the effect of exercise therapy, over half of patients have been on monotherapy. No study has exclusively assessed the effect of exercise training in addition to optimal PAH therapy.
Sponsor: National Health Service, United Kingdom
Current Primary Outcome:
- 6 minute walk distance [ Time Frame: 15 weeks ]Change in distance walked in 6 minutes from baseline following 15 weeks of exercise therapy
- Quality of life [ Time Frame: 15 weeks ]Change in pulmonary hypertension specific (EMPHASIS and CAMPHOR) and generic (SF-36 v2) quality of life scores from baseline to 15 weeks following exercise therapy.
- Right Ventricular Ejection Fraction [ Time Frame: 15 weeks ]Change in right ventricular ejection fraction from baseline to 15 weeks as measured by cardiac magnetic resonance imaging.
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Peak oxygen uptake [ Time Frame: 15 weeks ]Peak oxygen uptake as measured by standard incremental cardiopulmonary exercise testing (CPET) at 15 weeks in addition to all other standard CPET variables
- Muscle strength and endurance [ Time Frame: 15 weeks ]change in quadriceps strength and endurance, and hand grip endurance and strength from baseline to 15 weeks, as measured by a myometer
- Transfer factor for lung carbon monoxide [ Time Frame: 3 weeks ]Transfer factor for lung carbon monoxide as measured during standard pulmonary function testing. Change from baseline to 3 weeks.
- Respiratory muscle strength [ Time Frame: 3 weeks ]change maximum inspiratory and maximum expiratory pressure measured following 3 weeks of exercise therapy.
- Pulmonary vascular resistance [ Time Frame: 15 weeks ]Change from baseline to 15 weeks, of pulmonary vascular resistance and total pulmonary resistance as measured during resting and exercise right heart catheterisation
- Cardiac Output at rest and peak exercise [ Time Frame: 15 weeks ]Change in cardiac output from baseline to 15 weeks as measured by right heart catheterisation at rest and on supine exercise
- Change in resting and peak exercise mixed venous oxygen saturation [ Time Frame: 15 weeks ]Change in mixed venous oxygen saturation from baseline to week 15, as measured from the central pulmonary artery during resting and exercise right heart catheterisation.
- Left ventricular ejection fraction [ Time Frame: 15 weeks ]Left ventricular ejection fraction as measured by cardiac MRI - change from baseline to 15 weeks following exercise therapy
Original Secondary Outcome: Same as current
Information By: National Health Service, United Kingdom
Dates:
Date Received: November 8, 2016
Date Started: February 2016
Date Completion: November 2017
Last Updated: November 22, 2016
Last Verified: November 2016
- 6 minute walk distance [ Time Frame: 15 weeks ]
