Clinical trial NCT04241497: Home-based Exercise Training in Patients With Pulmonary Arterial Hypertension: Effect on Skeletal Muscular Function and Metabolism
Official title: Home-based Exercise Training in Patients With Pulmonary Arterial Hypertension: Effect on Skeletal Muscular Function and Metabolism
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Pulmonary Arterial Hypertension
Exercise Training
Home-based Rehabilitation
Exercise Capacity
Muscle Metabolism
Muscle Function
Lipid Infiltration
Oxidative Metabolism
Lead sponsor: Laval University
Sponsor class: OTHER
First posted: 2020-01-27
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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)

Eligibility criteria: 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

Primary outcomes:
measure: Epigenetic factors influencing muscle metabolism
timeFrame: Changes between baseline and 12 weeks of exercise rehabilitation
Secondary outcomes:
measure: Intramyocellular lipid accumulation
timeFrame: Changes between baseline and 12 weeks of exercise rehabilitation
measure: Muscular mitochondrial phosphorylation (ATP synthesis)
timeFrame: Changes between baseline and 12 weeks of exercise rehabilitation
measure: Proportion of muscle fiber types
timeFrame: Changes between baseline and 12 weeks of exercise rehabilitation
measure: HbA1c
timeFrame: Changes between baseline and 12 weeks of exercise rehabilitation
measure: Insulin
timeFrame: Changes between baseline and 12 weeks of exercise rehabilitation
measure: Glucose
timeFrame: Changes between baseline and 12 weeks of exercise rehabilitation
measure: Apolipoprotein A1
timeFrame: Changes between baseline and 12 weeks of exercise rehabilitation
measure: Adiponectin
timeFrame: Changes between baseline and 12 weeks of exercise rehabilitation
measure: Leptin
timeFrame: Changes between baseline and 12 weeks of exercise rehabilitation
measure: Volitional strength quadriceps
timeFrame: Changes between baseline and 12 weeks of exercise rehabilitation
measure: Non-volitional strength of the quadriceps
timeFrame: Changes between baseline and 12 weeks of exercise rehabilitation
measure: Maximal exercise capacity
timeFrame: Changes between baseline and 12 weeks of exercise rehabilitation
measure: Functional Exercise capacity
timeFrame: Changes between baseline and 12 weeks of exercise rehabilitation
measure: Quality of life (QOL)
timeFrame: Changes between baseline and 12 weeks of exercise rehabilitation
Other outcomes:
Locations:
city: Québec
country: Canada
facility: University Institute of Cardiology and Respirology of Quebec
Study officials:
References:
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