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

Pulmonary Arterial Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04241497
• Other study ID #: HTAP A DOM
• Status: Not yet recruiting
• Phase: N/A
• Start date: March 2020
• Est. completion date: March 2021

Study information

• Verified date: January 2020
• Source: Laval University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 10
• Est. completion date: March 2021
• Est. primary completion date: March 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Exercise Capacity
• Exercise Training
• Familial Primary Pulmonary Hypertension
• Home-based Rehabilitation
• Hypertension
• Lipid Infiltration
• Muscle Function
• Muscle Metabolism
• Oxidative Metabolism
• Pulmonary Arterial Hypertension

Intervention

Behavioral:
• Home-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)

Locations

Country	Name	City	State
Canada	University Institute of Cardiology and Respirology of Quebec	Québec

Sponsors (1)

Lead Sponsor	Collaborator
Laval University

Country where clinical trial is conducted

Canada, 

References & Publications (6)

Ehlken N, Lichtblau M, Klose H, Weidenhammer J, Fischer C, Nechwatal R, Uiker S, Halank M, Olsson K, Seeger W, Gall H, Rosenkranz S, Wilkens H, Mertens D, Seyfarth HJ, Opitz C, Ulrich S, Egenlauf B, Grünig E. Exercise training improves peak oxygen consump — View Citation

Grünig E, Eichstaedt C, Barberà JA, Benjamin N, Blanco I, Bossone E, Cittadini A, Coghlan G, Corris P, D'Alto M, D'Andrea A, Delcroix M, de Man F, Gaine S, Ghio S, Gibbs S, Gumbiene L, Howard LS, Johnson M, Jureviciene E, Kiely DG, Kovacs G, MacKenzie A, — View Citation

Grünig E, Lichtblau M, Ehlken N, Ghofrani HA, Reichenberger F, Staehler G, Halank M, Fischer C, Seyfarth HJ, Klose H, Meyer A, Sorichter S, Wilkens H, Rosenkranz S, Opitz C, Leuchte H, Karger G, Speich R, Nagel C. Safety and efficacy of exercise training — View Citation

Malenfant S, Brassard P, Paquette M, Le Blanc O, Chouinard A, Nadeau V, Allan PD, Tzeng YC, Simard S, Bonnet S, Provencher S. Compromised Cerebrovascular Regulation and Cerebral Oxygenation in Pulmonary Arterial Hypertension. J Am Heart Assoc. 2017 Oct 12 — View Citation

Malenfant S, Potus F, Fournier F, Breuils-Bonnet S, Pflieger A, Bourassa S, Tremblay È, Nehmé B, Droit A, Bonnet S, Provencher S. Skeletal muscle proteomic signature and metabolic impairment in pulmonary hypertension. J Mol Med (Berl). 2015 May;93(5):573- — View Citation

Potus F, Malenfant S, Graydon C, Mainguy V, Tremblay È, Breuils-Bonnet S, Ribeiro F, Porlier A, Maltais F, Bonnet S, Provencher S. Impaired angiogenesis and peripheral muscle microcirculation loss contribute to exercise intolerance in pulmonary arterial h — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Epigenetic factors influencing muscle metabolism	Transcriptome analysis using RNA-seq	Changes between baseline and 12 weeks of exercise rehabilitation
Secondary	Intramyocellular lipid accumulation	H-magnetic resonance spectroscopy and Oil red O technique	Changes between baseline and 12 weeks of exercise rehabilitation
Secondary	Muscular mitochondrial phosphorylation (ATP synthesis)	phosphorus-31 Magnetic resonance spectroscopy saturation transfer	Changes between baseline and 12 weeks of exercise rehabilitation
Secondary	Proportion of muscle fiber types	Ethanol modified technique	Changes between baseline and 12 weeks of exercise rehabilitation
Secondary	HbA1c	Serum HbA1c	Changes between baseline and 12 weeks of exercise rehabilitation
Secondary	Insulin	Serum Insulin	Changes between baseline and 12 weeks of exercise rehabilitation
Secondary	Glucose	Serum glucose	Changes between baseline and 12 weeks of exercise rehabilitation
Secondary	Apolipoprotein A1	Serum Apolipoprotein A1	Changes between baseline and 12 weeks of exercise rehabilitation
Secondary	Adiponectin	Serum Adiponectin	Changes between baseline and 12 weeks of exercise rehabilitation
Secondary	Leptin	Serum leptin	Changes between baseline and 12 weeks of exercise rehabilitation
Secondary	Volitional strength quadriceps	Maximal Voluntary force using isometric force meter	Changes between baseline and 12 weeks of exercise rehabilitation
Secondary	Non-volitional strength of the quadriceps	Maximal non-Voluntary force using isometric force meter and magnetic stimulation of the femoral neve	Changes between baseline and 12 weeks of exercise rehabilitation
Secondary	Maximal exercise capacity	Cardio-pulmonary exercise testing on a cycloergometer	Changes between baseline and 12 weeks of exercise rehabilitation
Secondary	Functional Exercise capacity	6-MWD	Changes between baseline and 12 weeks of exercise rehabilitation
Secondary	Quality of life (QOL)	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	Changes between baseline and 12 weeks of exercise rehabilitation