Micro-environment Involvement in Muscle Alteration Induced

Chronic Obstructive Pulmonary Disease Clinical Trial

— MicAMI-BPCO  

Official title:

Micro-environment Involvement in Muscle Alteration Induced by Copd Exacerbation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04448626
• Other study ID #: RECHMPL20_0137
• Status: Completed
• Start date: March 1, 2020
• Est. completion date: May 30, 2020

Study information

• Verified date: June 2020
• Source: University Hospital, Montpellier
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: May 30, 2020
• Est. primary completion date: May 1, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 85 Years

Eligibility

Inclusion criteria 1/ for COPD patients hospitalized for exacerbation:

• 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

Related Conditions & MeSH terms

• Atrophy
• Chronic Obstructive Pulmonary Disease
• Exacerbations
• Lung Diseases, Obstructive
• Muscular Atrophy
• Pulmonary Disease, Chronic Obstructive
• Skeletal Muscle Atrophy

Locations

Country	Name	City	State
France	Uhmontpellier	Montpellier

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Montpellier	APARD Fonds de dotation

Country where clinical trial is conducted

France, 

References & Publications (4)

Catteau M, Gouzi F, Blervaque L, Passerieux E, Blaquière M, Ayoub B, Bughin F, Mercier J, Hayot M, Pomiès 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. — View Citation

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. Epub 2007 Sep 20. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Identification of one (or more) circulating biomarker (s)	Identification of one (or more) circulating biomarker (s) that may be responsible for the muscle alteration induced by the microenvironment of patient in exacerbation of COPD	3 months