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Home-based Exercise Training in Patients With Pulmonary Arterial Hypertension: Effect on Skeletal Muscular Function and Metabolism

Not Applicable
Conditions
Lipid Infiltration
Pulmonary Arterial Hypertension
Muscle Metabolism
Muscle Function
Exercise Training
Oxidative Metabolism
Home-based Rehabilitation
Exercise Capacity
Interventions
Behavioral: Home-based rehabilitation
Registration Number
NCT04241497
Lead Sponsor
Laval University
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)

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
10
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Patients with Pulmonary Arterial HypertensionHome-based rehabilitation12 weeks home-based rehabilitation
Primary Outcome Measures
NameTimeMethod
Epigenetic factors influencing muscle metabolismChanges between baseline and 12 weeks of exercise rehabilitation

Transcriptome analysis using RNA-seq

Secondary Outcome Measures
NameTimeMethod
HbA1cChanges between baseline and 12 weeks of exercise rehabilitation

Serum HbA1c

Intramyocellular lipid accumulationChanges between baseline and 12 weeks of exercise rehabilitation

H-magnetic resonance spectroscopy and Oil red O technique

Proportion of muscle fiber typesChanges between baseline and 12 weeks of exercise rehabilitation

Ethanol modified technique

Muscular mitochondrial phosphorylation (ATP synthesis)Changes between baseline and 12 weeks of exercise rehabilitation

phosphorus-31 Magnetic resonance spectroscopy saturation transfer

InsulinChanges between baseline and 12 weeks of exercise rehabilitation

Serum Insulin

GlucoseChanges between baseline and 12 weeks of exercise rehabilitation

Serum glucose

Non-volitional strength of the quadricepsChanges between baseline and 12 weeks of exercise rehabilitation

Maximal non-Voluntary force using isometric force meter and magnetic stimulation of the femoral neve

Apolipoprotein A1Changes between baseline and 12 weeks of exercise rehabilitation

Serum Apolipoprotein A1

AdiponectinChanges between baseline and 12 weeks of exercise rehabilitation

Serum Adiponectin

Volitional strength quadricepsChanges between baseline and 12 weeks of exercise rehabilitation

Maximal Voluntary force using isometric force meter

Functional Exercise capacityChanges between baseline and 12 weeks of exercise rehabilitation

6-MWD

LeptinChanges between baseline and 12 weeks of exercise rehabilitation

Serum leptin

Maximal exercise capacityChanges between baseline and 12 weeks of exercise rehabilitation

Cardio-pulmonary exercise testing on a cycloergometer

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

Trial Locations

Locations (1)

University Institute of Cardiology and Respirology of Quebec

🇨🇦

Québec, Canada

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