Influence of Chronic Hypoxia on Oxidative Phenotype in Patients With Chronic Obstructive Pulmonary Disease

Terminated

• Conditions: Chronic Obstructive Pulmonary Disease
• Interventions: Procedure: Muscle biopsy

• Registration Number: NCT02532426
• Lead Sponsor: Centre Hospitalier Universitaire de Saint Etienne

Brief Summary

In addition to chronic airflow obstruction, patients with Chronic Obstructive Pulmonary Disease (COPD) suffer from skeletal muscle dysfunction which is a prominent and disabling feature and also an independent determinant of survival. Muscular impairment involves loss of muscle oxidative phenotype (OXPHEN: a slow-to-fast shift in fibre types and reduced oxidative capacity). Since hypoxia obviously is a key feature of COPD, the aim of this study is to elucidate the role of hypoxia in loss of muscle OXPHEN.

Thus, OXPHEN and expression levels of its key regulators will be determined in the baseline biopsies for association with the degree of hypoxemia. In addition, expression levels of the key OXPHEN regulators will be measured in pre/post exercise biopsies.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-05-18
• Study First Submitted: 2015-08-21
• Study First Submitted QC: 2015-08-21
• Study First Posted: 2015-08-25
• Primary Completion: 2017-09-30
• Study Completion: 2017-09-30
• Status Verified: 2017-10
• Last Update Submitted: 2017-10-17
• Last Update Posted: 2017-10-19

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 13

Inclusion Criteria

• Diagnosis of COPD confirmed according to GOLD score.
• Hypoxemia group: resting arterial paO2 <55 mmHg.
• Normoxemia group : resting arterial paO2 > 67 mmHg

Exclusion Criteria

• Unstable cardiorespiratory status (acute respiratory failure)
• Oxygen treatment started
• Inclusion in a pulmonary rehabilitation program in the last 6 months
• Anticoagulant treatment

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
COPD patients with chronic hypoxemia	Muscle biopsy	COPD patients with chronic and severe arterial hypoxemia at rest (paO2\<55mmHg).
COPD patients with normoxia	Muscle biopsy	COPD patients with normoxia at rest (paO2\>67mmHg), matched for age, sex, bronchial obstruction and lean mass.

Primary Outcome Measures

Name	Time	Method
Level of expression of muscle messenger ribonucleic acid (mRNA) of HIF-1α and PGC-1α	Day 1	Comparison of expression levels of Hypoxia-inducible Factors (HIF-1α) and Peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC-1α), two OXYPHEN regulators, in muscle biopsy, between COPD patients with chronic hypoxemia and those with normoxemia

Secondary Outcome Measures

Name	Time	Method
Oxidative enzyme capacity	Day 1	It is an other indicator of the muscle phenotype (with a muscle biopsy). It used to compared the muscle phenotype in the 2 groups of patients.
Level of expression of muscle mRNA of PGC-1α after acute exercise	Day 1	Comparison of response to acute exercise for expression level of PGC-1α (an OXYPHEN regulator) in muscle biopsy between the 2 groups.
Type I muscle fibers	Day 1	It is an indicator of the muscle phenotype (with a muscle biopsy). It used to compared the muscle phenotype in the 2 groups of patients. It is a percentage.
Level of expression of muscle mRNA of HIF-1α after acute exercise	Day 1	Comparison of response to acute exercise for expression level of HIF-1α (an OXYPHEN regulator) in muscle biopsy between the 2 groups.

Trial Locations

Locations (1)

CHU de Saint-Etienne; 🇫🇷 Saint-etienne, France