Physiopathology of Lower Cortical Activation in COPD Patients: Contribution of Cortical Neuromodulation

Patients with COPD have lower cortical activation and higher cortical inhibitory levels. The purpose of this study is to test the reversibility the lower cortical activation by counterbalancing the increased cortical inhibitory levels with neuro-modulation.

Study Overview

• Status: Completed
• Conditions: Physiology
• Intervention / Treatment: Device: Anodal transcranial direct-current-stimulation; Device: Sham transcranial direct-current-stimulation

Detailed Description

Chronic obstructive pulmonary disease (COPD) patients exhibit not only respiratory symptoms but also a peripheral muscular weakness. This weakness is characterized by a loss in strength, harmful for the patients' life quality and vital prognostic. Even if many papers have enlightened damages at a peripheral level, the muscular atrophy itself cannot totally explain the loss in force. Furthermore, the contractile properties of COPD muscles fibres are preserved. Consequently, it seems that the peripheral muscle weakness cannot only be explained by peripheral factors and central structures may be involved.

A recent work showed that during quadriceps voluntary contraction, cortical activation in COPD patients was significantly lower than in healthy subjects, contributing in the loss in strength. However, the pathophysiology underlying this loss of strength is still unclear and two hypotheses can be advanced: 1) the influence of anatomical lesions in the brain of COPD patients and 2) the particular metabolism of this population. Indeed, COPD patients show a reduced oxidative activity and an increased glycolytic contribution (decreased type I fibres and increased type II fibres, increased glycolytic enzymes activity, increased metabolites production). This specific metabolic may lead to an over-activation of type III-IV afferents, projecting onto somatosensory cortex sensitive to metabolites at a peripheral level, and produce inhibitory activity on the primary motor cortex, seat of the motor control. What is reported in the literature so far, is that COPD patients display increased cortical inhibitory values than healthy subjects.

Therefore, beyond understanding better the nervous mechanisms involved in the COPD's peripheral muscle weakness, the aim of this study is to counterbalance this increased cortical inhibitory level.

We hypothesize that modulating inhibitory processes at a cortical level would induced a reduction of inhibitions in patients with COPD and an increase in the force produced. In case this hypothesis would be verified, we will be able to confirm that this increased cortical level in COPD patients is reversible and may be a target for rehabilitation.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Herault
    • Lodeve, Herault, France, 34700
      • Cliniques du Souffle

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Health insurance
• Patients : COPD Gold II-IV
• Patients : No rehabilitation since at least 1 yrs
• Control : sedentary (< 9 Voorips)

Exclusion Criteria:

• Pregnant women
• Seizures
• Unable to give written consent
• Metalic object above shoulders
• Dermatological issue concerning surface electrodes
• Drugs influencing central nervous system
• Caffeine consumption > 4 coffee / day
• Neurological disorders
• Patients : recent exacerbation (< 4 weeks)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: COPD patients; COPD patients group	Device: Anodal transcranial direct-current-stimulation; 2mA / 20min Anodal and Sham tDCS over dominant M1. Anodal tDCS consists of 30s of ramp up followed by 20min of stimulation and 30s of ramp down.; Device: Sham transcranial direct-current-stimulation; Sham tDCS consists of only 30s of ramp up followed by 30s of ramp down and no further stimulation. Participants therefore have the same feeling for both modalities : slight itching due to the induced current at the beginning of the protocol (during around 30s) allowing no differentiation by the participant between the anodal or sham sessions.
Active Comparator: Healthy subjects; Healthy subject group, matched with COPD patients group on age, weight and BMI	Device: Anodal transcranial direct-current-stimulation; 2mA / 20min Anodal and Sham tDCS over dominant M1. Anodal tDCS consists of 30s of ramp up followed by 20min of stimulation and 30s of ramp down.; Device: Sham transcranial direct-current-stimulation; Sham tDCS consists of only 30s of ramp up followed by 30s of ramp down and no further stimulation. Participants therefore have the same feeling for both modalities : slight itching due to the induced current at the beginning of the protocol (during around 30s) allowing no differentiation by the participant between the anodal or sham sessions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in motor-evoked potentials	Cortical excitability	Baseline (pre-intervention) ; Post-Stim (immediately post-intervention) ; Post-30 (30min post-intervention)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in short-interval intracortical inhibition	Cortical inhibition level	Baseline (pre-intervention) ; Post-Stim (immediately post-intervention) ; Post-30 (30min post-intervention)
Change in cortical silent period	Cortical inhibition level	Baseline (pre-intervention) ; Post-Stim (immediately post-intervention) ; Post-30 (30min post-intervention)
Change in cortical voluntary activation	Motor command	Baseline (pre-intervention) ; Post-Stim (immediately post-intervention) ; Post-30 (30min post-intervention)
Change in strength	Functional output	Baseline (pre-intervention) ; Post-Stim (immediately post-intervention) ; Post-30 (30min post-intervention)

Collaborators and Investigators

• Sponsor: 5 Santé
• Investigators: Principal Investigator: Philippe Guerin, MD, 5 Santé

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2017
• Primary Completion (Actual): June 30, 2018
• Study Completion (Actual): June 30, 2018

Study Registration Dates

• First Submitted: December 19, 2016
• First Submitted That Met QC Criteria: December 8, 2017
• First Posted (Actual): December 11, 2017

Study Record Updates

• Last Update Posted (Actual): January 13, 2020
• Last Update Submitted That Met QC Criteria: January 10, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: COPD; Transcranial magnetic stimulation; Inhibition; Muscle weakness; Motor-evoked potentials; Transcranial direct-current stimulation
• Other Study ID Numbers: 5S_EXCCOM

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No