Exercise Capacity, Exercise Training, Home-based Rehabilitation, Lipid Infiltration, Muscle Function, Muscle Metabolism, Oxidative Metabolism, Pulmonary Arterial Hypertension
Conditions
Brief summary
Pulmonary Arterial Hypertension has gone from a disease that causes rapid death to a more chronic condition. Yet, improved survival is associated with major challenges for clinicians as most patients remain with poor quality of life and limited exercise capacity. The effects of exercise training on exercise capacity have been largely evaluated and showed an improvement in 6-minutes walking distance (6MWD), peak V'O2. It is also known that exercise program improves quality of life. Maximal volitional and nonvolitional strength of the quadriceps are reduced in patients with Pulmonary Arterial Hypertension and correlated to exercise capacity. Moreover, on the cellular level, alterations are observed in both the respiratory as well as the peripheral muscles. Muscle fiber size has been reported to be decreased in some studies or conversely unaltered in human and animal models. Reduction in type I fibers and a more anaerobic energy metabolism has also been reported, but not in all studies. Likewise, a loss in capillary density in quadriceps of patients with Pulmonary Arterial Hypertension and rats has been reported, but could not be confirmed in other studies. While the impact of exercise training on clinical outcomes such as exercise capacity or quality of life is well known, this data highlight the fact that the underlying causes of peripheral muscle weakness as well as the mechanisms underlying the clinical improvements observed with exercise programs are not completely understood. Improvement of muscle cell metabolism in part via the enhancement of oxidative cellular metabolism and decrease in intracellular lipid accumulation may play a role in improving muscle function and exercise capacity. In this study, we intend to evaluate the impact of a 12 weeks home-based rehabilitation program on peripheral muscle function and metabolism, focusing on lipid infiltration, oxidative metabolism and epigenetic factors that can be involved in metabolic syndrome, in patients with Pulmonary Arterial Hypertension.
Detailed description
The 12 weeks home-based rehabilitation program is detailed as follows: * 1st sessions at the hospital, in the presence of a physiotherapist/kinesiologist * 3 weeks of supervised home-based rehabilitation (using a telemonitoring system) 3 times a weeks * 9 weeks of unsupervised home-based rehabilitation (one phone call a week) Patients will be evaluated at baseline and at endpoint (12 weeks)
Interventions
BEHAVIORALHome-based rehabilitation
1 supervised exercise session at the hospital; 3 weeks of supervised home-based exercise training (3x/week); 9 weeks of unsupervised home-based exercise training (3x/week)
Sponsors
Laval University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Men or women \> 18 years old * Pulmonary Arterial Hypertension group 1: idiopathic, genetics, drug or toxin-induced, associated with connective tissue, HIV, portal hypertension, congenital heart disease. * Diagnosis performed by right heart catheterization with Pulmonary Arterial Pressure⩾ 20 mmHg, pulmonary artery occlusion pressure \<15 and pulmonary vascular resistance \>3 Wood units * New York Heart Association II or III and a 6-Minute Walk Test \< 500m * Patient stable without therapeutic modification within the last 3 months * Patient having wireless internet at home * Consciously informed and written by the patient
Exclusion criteria
* Syncope within the last 6 month * Metabolic comorbidity (eg Diabetes) * Musculoskeletal impairment that does not allow physical exercise * Patient unable or with contraindications to perform a cardio pulmonary exercise testing * Patient with pulmonary veno-occlusive disease * Presence of a permanent pacemaker or other contraindication to MRI * Pregnant or breastfeeding woman * Age \<18 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Epigenetic factors influencing muscle metabolism | Changes between baseline and 12 weeks of exercise rehabilitation | Transcriptome analysis using RNA-seq |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Muscular mitochondrial phosphorylation (ATP synthesis) | Changes between baseline and 12 weeks of exercise rehabilitation | phosphorus-31 Magnetic resonance spectroscopy saturation transfer |
| Proportion of muscle fiber types | Changes between baseline and 12 weeks of exercise rehabilitation | Ethanol modified technique |
| HbA1c | Changes between baseline and 12 weeks of exercise rehabilitation | Serum HbA1c |
| Insulin | Changes between baseline and 12 weeks of exercise rehabilitation | Serum Insulin |
| Glucose | Changes between baseline and 12 weeks of exercise rehabilitation | Serum glucose |
| Apolipoprotein A1 | Changes between baseline and 12 weeks of exercise rehabilitation | Serum Apolipoprotein A1 |
| Intramyocellular lipid accumulation | Changes between baseline and 12 weeks of exercise rehabilitation | H-magnetic resonance spectroscopy and Oil red O technique |
| Leptin | Changes between baseline and 12 weeks of exercise rehabilitation | Serum leptin |
| Volitional strength quadriceps | Changes between baseline and 12 weeks of exercise rehabilitation | Maximal Voluntary force using isometric force meter |
| Non-volitional strength of the quadriceps | Changes between baseline and 12 weeks of exercise rehabilitation | Maximal non-Voluntary force using isometric force meter and magnetic stimulation of the femoral neve |
| Maximal exercise capacity | Changes between baseline and 12 weeks of exercise rehabilitation | Cardio-pulmonary exercise testing on a cycloergometer |
| Functional Exercise capacity | Changes between baseline and 12 weeks of exercise rehabilitation | 6-MWD |
| Quality of life (QOL) | Changes between baseline and 12 weeks of exercise rehabilitation | Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) questionnaire. The CAMPHOR questionnaire contains 65 items in total, 25 relating to symptoms, 15 relating to activities, and 25 relating to QoL. It is negatively weighted; a higher score indicates worse QoL and greater functional limitation. Symptom and QoL items are both scored out of 25: yes/true scores 1 and no/not true scores 0. Activity items have three possible responses (score 0-2), giving a score out of 30. Each CAMPHOR assessment takes an average of 10 min |
| Adiponectin | Changes between baseline and 12 weeks of exercise rehabilitation | Serum Adiponectin |
Countries
Canada
Outcome results
None listed