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

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.

Study Overview

• Status: Terminated
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Procedure: Muscle biopsy

• Study Type: Observational
• Enrollment (Actual): 13

Contacts and Locations

Study Locations

• France
  • Saint-etienne, France, 42000
    • CHU de Saint-Etienne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

COPD patients with chronic hypoxemia and with normoxemia

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
COPD patients with chronic hypoxemia; COPD patients with chronic and severe arterial hypoxemia at rest (paO2<55mmHg).	Procedure: Muscle biopsy; The biopsy is performed on the vastus lateralis muscle at rest and 2 hours after an acute exercise, with a local anesthesia.
COPD patients with normoxia; COPD patients with normoxia at rest (paO2>67mmHg), matched for age, sex, bronchial obstruction and lean mass.	Procedure: Muscle biopsy; The biopsy is performed on the vastus lateralis muscle at rest and 2 hours after an acute exercise, with a local anesthesia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Level of expression of muscle messenger ribonucleic acid (mRNA) of HIF-1α and PGC-1α	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	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Type I muscle fibers	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.	Day 1
Oxidative enzyme capacity	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.	Day 1
Level of expression of muscle mRNA of HIF-1α after acute exercise	Comparison of response to acute exercise for expression level of HIF-1α (an OXYPHEN regulator) in muscle biopsy between the 2 groups.	Day 1
Level of expression of muscle mRNA of PGC-1α after acute exercise	Comparison of response to acute exercise for expression level of PGC-1α (an OXYPHEN regulator) in muscle biopsy between the 2 groups.	Day 1

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Collaborators: SYNAPSE assocation
• Investigators: Principal Investigator: COSTES Frédéric, MD PhD, CHU de Saint-Etienne

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2012
• Primary Completion (Actual): September 30, 2017
• Study Completion (Actual): September 30, 2017

Study Registration Dates

• First Submitted: August 21, 2015
• First Submitted That Met QC Criteria: August 21, 2015
• First Posted (Estimate): August 25, 2015

Study Record Updates

• Last Update Posted (Actual): October 19, 2017
• Last Update Submitted That Met QC Criteria: October 17, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Exercise; Chronic Obstructive Pulmonary Disease; Muscle biopsy; Chronic hypoxia; OXYPHEN; Oxydative phenotype
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Hypoxia
• Other Study ID Numbers: 1108100; 2011-A00856-35 (Other Identifier: AFSSAPS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No