Micro-environment Involvement in Muscle Alteration Induced

NCT ID: NCT04448626

Last Updated: 2020-06-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

27 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-03-01

Study Completion Date

2020-05-30

Brief Summary

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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.

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Detailed Description

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Conditions

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Chronic Obstructive Pulmonary Disease Exacerbations Skeletal Muscle Atrophy

Study Design

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Observational Model Type

OTHER

Study Time Perspective

RETROSPECTIVE

Study Groups

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Healthy subject

Healthy subject

No interventions assigned to this group

Stable COPD patients

Stable COPD patients

No interventions assigned to this group

Exacerbation COPD patients

Exacerbation COPD patients

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* 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)

Exclusion Criteria

1. 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
2. for COPD patients

* Exacerbation with récent hospitalization (\<4 weeks)
* Neurologic comorbidity
3. for Healthy subjects - long term drug treatment with proven central effects
Minimum Eligible Age

40 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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APARD Fonds de dotation

OTHER

Sponsor Role collaborator

University Hospital, Montpellier

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Maurice HAYOT, MD, PhD

Role: STUDY_DIRECTOR

University Hospital, Montpellier

Locations

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Uhmontpellier

Montpellier, , France

Site Status

Countries

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France

References

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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.

Reference Type BACKGROUND
PMID: 12947130 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20332630 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17883420 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32173533 (View on PubMed)

Other Identifiers

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RECHMPL20_0137

Identifier Type: -

Identifier Source: org_study_id

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