Micro-environment Involvement in Muscle Alteration Induced

NCT04448626 | Completed

• 1 other identifier: RECHMPL20_0137
• Study Type: observational
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic Obstructive Pulmonary Disease (COPD) is characterized by persistent airway obstruction and inflammatory response of the lungs and bronchi. Episodes of exacerbations contribute to increase the severity and prognosis of the disease. Muscle dysfunction (loss of strengh and muscle mass) is one of comorbidities affecting 30% to 60% of patients and playing a key role in their prognosis. During exacerbation, some studies have suggested an association between muscle dysfunction and modifications of inflammatory circulating factors such as CRP, TNF-alpha, IL- 6, IL8, but no exhaustive study has identified precisely one (or more) biomarker(s) that can induce this muscle wasting during the exacerbation of COPD. Our hypothesis is that the serum of exacerbated COPD patients represents a deleterious microenvironment for the muscle cells which would amplify the mechanisms of atrophy linked to hospitalization. Our team has already developed a cell culture model to study the effects of the plasma microenvironment on atrophy of cultured myotubes. The investigators have shown that the serum of COPD patients can induce muscle atrophy. The objectives of this study are : 1/ to evaluate the effects of circulating pro-inflammatory factors on atrophy and the myogenic capacities of muscle cells; and 2/ to identify one (or more) circulating biomarker (s) that may be responsible for the muscle damage induced by the microenvironment of hospitalized patients for exacerbation of COPD. First, myotubes and myoblasts of healthy subjects will be cultivated with 9 exacerbation copd patient serum or 9 copd patient serum or 9 healthy subject serum. Myotube diameters, atrophy, inflammatory and oxidative stress markers and alteration of the myogenic capacity of satellite cells will be compared between three groups. Second, the differential expression of circulating proinflammatory molecules will be compared in the serum of the three groups. Identifying circulating factors associated with muscle weakness is a necessary step to better understand the mechanisms and consider a personalized therapeutic approach that can improve the functional and clinical prognosis of disease. .

Conditions

Chronic Obstructive Pulmonary Disease; Exacerbations; Skeletal Muscle Atrophy

Keywords

COPD Exacerbation; Muscle atrophy; Inflammation; Oxidative stress; Biomarkers

Outcome Measures

Primary Outcomes (2)

• Effects evaluation of circulating pro-inflammatory factors on atrophy

  Atrophy marker evaluation in cultured muscle cells (myotubes) * cultured myotube diameter exposed to the three serum groups (immunofluorescence) * atrophy (ubiquitin proteasome system, proteolytic autophagy pathway), inflammatory (TNF-alpha, IL-6, IL-8…) and oxidative stress (ROS, lipid peroxidation) markers expressed by cells exposed to the three serum groups (PCR et WesternBlot)

  6 months

• Effects evaluation of circulating pro-inflammatory factors on the myogenic capacities of muscle cells

  Myogenic capacities of cultured muscle cells (myoblastes) * inflammatory (TNF-alpha, IL-6, IL-8…) and oxidative stress (ROS, lipid peroxidation) markers expressed by cells exposed to the three serum groups (PCR et WesternBlot) * regeneration markers (Notch and myogenesis signaling pathways) expressed by cells exposed to the three serum groups (PCR et WesternBlot)

  6 months

Secondary Outcomes (1)

• Identification of one (or more) circulating biomarker (s)

  3 months

Study Arms (3)

Healthy subject

Healthy subject

Stable COPD patients

Stable COPD patients

Exacerbation COPD patients

Exacerbation COPD patients

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

COPD patients hospitalized for exacerbation in Montpellier university hospital, France. COPD patients recruited in Clinique du Souffle, La Vallonie, Lodève, France. Healthy volunteer subject recruited in Clinique du Souffle, La Vallonie, Lodève, France.

You may qualify if:

• Hospitalization for COPD exacerbation 2/ for COPD patients
• COPD patients GOLD II à IV
• Not having followed respiratory réhabilitation stay for at least one year 3/ for Healthy subjects
• healthy and sedentary (Voorips score \<9)

You may not qualify if:

• for COPD patients hospitalized for exacerbation:
• concomitant acute cardiac évent
• trachéal intubation with mechanical ventilation
• chronic respiratory disease other than COPD
• locomotor, neurologic or psychiatric comorbidities
• for COPD patients
• Exacerbation with récent hospitalization (\<4 weeks)
• Neurologic comorbidity
• for Healthy subjects - long term drug treatment with proven central effects

Sponsors & Collaborators

• University Hospital, Montpellier: lead
• APARD Fonds de dotation: collaborator

Study Sites (1)

Uhmontpellier

Montpellier, 34295, France

Location

Related Publications (4)

• Spruit MA, Gosselink R, Troosters T, Kasran A, Gayan-Ramirez G, Bogaerts P, Bouillon R, Decramer M. Muscle force during an acute exacerbation in hospitalised patients with COPD and its relationship with CXCL8 and IGF-I. Thorax. 2003 Sep;58(9):752-6. doi: 10.1136/thorax.58.9.752.

  PMID: 12947130 BACKGROUND

• Crul T, Testelmans D, Spruit MA, Troosters T, Gosselink R, Geeraerts I, Decramer M, Gayan-Ramirez G. Gene expression profiling in vastus lateralis muscle during an acute exacerbation of COPD. Cell Physiol Biochem. 2010;25(4-5):491-500. doi: 10.1159/000303054. Epub 2010 Mar 23.

  PMID: 20332630 BACKGROUND

• Crul T, Spruit MA, Gayan-Ramirez G, Quarck R, Gosselink R, Troosters T, Pitta F, Decramer M. Markers of inflammation and disuse in vastus lateralis of chronic obstructive pulmonary disease patients. Eur J Clin Invest. 2007 Nov;37(11):897-904. doi: 10.1111/j.1365-2362.2007.01867.x. Epub 2007 Sep 20.

  PMID: 17883420 BACKGROUND

• Catteau M, Gouzi F, Blervaque L, Passerieux E, Blaquiere M, Ayoub B, Bughin F, Mercier J, Hayot M, Pomies P. Effects of a human microenvironment on the differentiation of human myoblasts. Biochem Biophys Res Commun. 2020 May 14;525(4):968-973. doi: 10.1016/j.bbrc.2020.03.020. Epub 2020 Mar 12.

  PMID: 32173533 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

serum

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Muscular Atrophy; Inflammation

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Signs and Symptoms

Study Officials

• Maurice HAYOT, MD, PhD

  University Hospital, Montpellier

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2020
• First Posted: June 26, 2020
• Study Start: March 1, 2020
• Primary Completion: May 1, 2020
• Study Completion: May 30, 2020
• Last Updated: June 26, 2020

Record last verified: 2020-06

Locations

FR (1)