The Effect of Adding Exercise Training to Optimal Therapy in Pulmonary Arterial Hypertension
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Quality of life
研究概览
简要总结
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
- Serum and muscle profile of inflammation
Primary outcomes (15 weeks)
- 6 minute walk distance
- QOL
- RV ejection fraction
详细描述
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.
B. Health care setting
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •World health organisation functional class (WHO-FC) II-III
- •Stable on optimal disease targeted therapy for ≥ 3 months
- •18 years of age or older
排除标准
- •Unable to provide informed consent
- •Significant peripheral vascular disease, neurological or musculoskeletal comorbidity
- •Exercise induced syncope, cardiac arrhythmia or chest pain
- •Pregnancy
- •Specific component exclusions: Cardiac MRI (CMR): Any contraindication to MRI
研究组 & 干预措施
Training
15 patients are randomised to receive 15 weeks exercise therapy as per study protocol at point of study entry.
干预措施: Exercise therapy (Other)
Control
15 patients are randomised to receive 15 weeks of standard care, acting as a control arm, followed by 15 weeks of exercise therapy.
干预措施: Exercise therapy (Other)
结局指标
主要结局
Quality of life
时间窗: 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.
6 minute walk distance
时间窗: 15 weeks
Change in distance walked in 6 minutes from baseline following 15 weeks of exercise therapy
Right Ventricular Ejection Fraction
时间窗: 15 weeks
Change in right ventricular ejection fraction from baseline to 15 weeks as measured by cardiac magnetic resonance imaging.
次要结局
- Peak oxygen uptake(15 weeks)
- Muscle strength and endurance(15 weeks)
- Transfer factor for lung carbon monoxide(3 weeks)
- Respiratory muscle strength(3 weeks)
- Pulmonary vascular resistance(15 weeks)
- Cardiac Output at rest and peak exercise(15 weeks)
- Change in resting and peak exercise mixed venous oxygen saturation(15 weeks)
- Left ventricular ejection fraction(15 weeks)
研究者
Martin Johnson
Dr Martin K Johnson
National Health Service, United Kingdom