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

NCT04241497 | Unknown

• 1 other identifier: HTAP A DOM
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Epigenetic factors influencing muscle metabolism

  Transcriptome analysis using RNA-seq

  Changes between baseline and 12 weeks of exercise rehabilitation

Secondary Outcomes (14)

• Intramyocellular lipid accumulation

  Changes between baseline and 12 weeks of exercise rehabilitation

• Muscular mitochondrial phosphorylation (ATP synthesis)

  Changes between baseline and 12 weeks of exercise rehabilitation

• Proportion of muscle fiber types

  Changes between baseline and 12 weeks of exercise rehabilitation

• HbA1c

  Changes between baseline and 12 weeks of exercise rehabilitation

• Insulin

  Changes between baseline and 12 weeks of exercise rehabilitation

Study Arms (1)

Patients with Pulmonary Arterial Hypertension

EXPERIMENTAL

12 weeks home-based rehabilitation

Behavioral: Home-based rehabilitation

Interventions

Home-based rehabilitation BEHAVIORAL

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)

Patients with Pulmonary Arterial Hypertension

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Laval University: lead

Study Sites (1)

University Institute of Cardiology and Respirology of Quebec

Québec, QC G1V 4G5, Canada

Location

Related Publications (6)

• Grunig 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 in various forms of pulmonary hypertension. Eur Respir J. 2012 Jul;40(1):84-92. doi: 10.1183/09031936.00123711. Epub 2012 Feb 9.

  PMID: 22323570 RESULT

• 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, Grunig E. Exercise training improves peak oxygen consumption and haemodynamics in patients with severe pulmonary arterial hypertension and inoperable chronic thrombo-embolic pulmonary hypertension: a prospective, randomized, controlled trial. Eur Heart J. 2016 Jan 1;37(1):35-44. doi: 10.1093/eurheartj/ehv337. Epub 2015 Jul 31.

  PMID: 26231884 RESULT

• Grunig E, Eichstaedt C, Barbera 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, Marra AM, McCaffrey N, McCaughey P, Naeije R, Olschewski H, Pepke-Zaba J, Reis A, Santos M, Saxer S, Tulloh RM, Ulrich S, Vonk Noordegraaf A, Peacock AJ. ERS statement on exercise training and rehabilitation in patients with severe chronic pulmonary hypertension. Eur Respir J. 2019 Feb 28;53(2):1800332. doi: 10.1183/13993003.00332-2018. Print 2019 Feb.

  PMID: 30578391 RESULT

• Potus F, Malenfant S, Graydon C, Mainguy V, Tremblay E, 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 hypertension. Am J Respir Crit Care Med. 2014 Aug 1;190(3):318-28. doi: 10.1164/rccm.201402-0383OC.

  PMID: 24977625 RESULT

• 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;6(10):e006126. doi: 10.1161/JAHA.117.006126.

  PMID: 29025748 RESULT

• Malenfant S, Potus F, Fournier F, Breuils-Bonnet S, Pflieger A, Bourassa S, Tremblay E, Nehme 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):573-84. doi: 10.1007/s00109-014-1244-0. Epub 2014 Dec 30.

  PMID: 25548805 RESULT

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Post-doctoral fellow

Study Record Dates

• First Submitted: January 22, 2020
• First Posted: January 27, 2020
• Study Start: March 1, 2020
• Primary Completion: March 1, 2021
• Study Completion: March 1, 2021
• Last Updated: January 28, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)