Influence of Muscular Atrophy on Biological and Functional Benefit of Respiratory Rehabilitation in Patients With Chronic Respiratory Failure (INSPIRE)

The prevalence of chronic respiratory failure (CRF) is increasing worldwide and will become the 3rd cause of death by 2020. At the stage of the disease requiring ventilatory assistance, this relates to 50,000 patients in France, life expectancy is very limited, and quality of life is poor.

CRF led to a reduction in muscle mass, which is found in 35 and 55% of patients, in some to a profound cachexia. A reduced fat free mass (FFM) is a factor associated with a poor tolerance to exercise and an halved survival. The exact causes and mechanisms leading to cachexia are not yet established. Recently, a chronic inflammatory condition has been quoted as a putative cause. This chronic inflammation would involve the molecular mechanisms leading to poor regulation of the balance of synthesis / protein degradation in muscle. A decrease in plasma and muscle amino acids was found among patients with a low FFM.. In addition, a decrease of plasma levels of some anabolic hormones, GH and androgens or IGF-1 has been found that could explain a lack of protein synthesis.

It is now well established that respiratory rehabilitation, including a program of exercise reconditioning, increases tolerance to exercise and improve the quality of life. Besides the classical type of endurance exercises stimulating the cardio-respiratory system, it is suggested to add resistance exercises. Several studies have reported the benefit of this strategy but the link with intracellular molecular pathways has not been described; moreover, it is unknown whether the existence of an initial muscular atrophy influences the gain in muscle strength/mass.

Study Overview

• Status: Completed
• Conditions: Respiratory Insufficiency
• Intervention / Treatment: Procedure: Respiratory rehabilitation

Detailed Description

We therefore propose to explore the effect of a rehabilitation program including endurance and resistance exercises on muscle biopsies.

The present study should help to know the molecular pathways implicated in muscle atrophy in CRF patients and to assess their evolution with rehabilitation. This could lead to individualized recommendation for exercise program according to the muscle mass of the patients.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Saint-etienne, France, 42055
    • CHU de SAINT-ETIENNE

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Prescription of an exercise training program as part of a respiratory rehabilitation
• Existence of an obstructive ventilatory deficit
• Signature of written consent

Exclusion Criteria:

• Exacerbation of COPD
• Patient with a long-term oxygen therapy
• Active smoker
• Lower limb locomotor limitation preventing to achieve the full respiratory rehabilitation program
• Lower limbs arteritis
• Myocardial infarction or pulmonary embolism of less than 3 months
• Long term anticoagulant
• Type 1 diabetes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Respiratory rehabilitation	Procedure: Respiratory rehabilitation; The training begins 5 days after the initial assessment. It consists of 3 weekly sessions for 8 consecutive weeks, including the following activities interspersed with periods of rest, according to the needs of patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Gain in exercise tolerance (relative variation of the 6 min walking distance and maximal exercise capacity on bicycle (peak VO2) combined with activation of the pathway for muscle protein synthesis	before and at the outcome of the reconditioning program in the effort

Secondary Outcome Measures

Outcome Measure	Time Frame
Quality of life assessed by questionnaire	before and at the outcome of the reconditioning program in the effort

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Collaborators: Ministry of Health, France
• Investigators: Principal Investigator: Frédéric COSTES, MD PhD, CHU de SAINT-ETIENNE

Publications and helpful links

General Publications

• Costes F, Gosker H, Feasson L, Desgeorges M, Kelders M, Castells J, Schols A, Freyssenet D. Impaired exercise training-induced muscle fiber hypertrophy and Akt/mTOR pathway activation in hypoxemic patients with COPD. J Appl Physiol (1985). 2015 Apr 15;118(8):1040-9. doi: 10.1152/japplphysiol.00557.2014. Epub 2015 Feb 19.

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: June 16, 2009
• First Submitted That Met QC Criteria: June 16, 2009
• First Posted (Estimate): June 17, 2009

Study Record Updates

• Last Update Posted (Estimate): July 24, 2014
• Last Update Submitted That Met QC Criteria: July 23, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Respiratory Insufficiency; Respiratory rehabilitation; Muscular Atrophy
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Neurologic Manifestations; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Respiratory Insufficiency; Muscular Atrophy; Atrophy
• Other Study ID Numbers: 0408079; 2005/0023 (Other Identifier: DGS)