MITAORTA - Role of Mitochondrial Dynamic in Aneurysm and Dissection of Ascending Thoracic Aorta

NCT ID: NCT05434481

Last Updated: 2024-06-11

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

ACTIVE_NOT_RECRUITING

Clinical Phase

NA

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-09-07

Study Completion Date

2024-10-23

Brief Summary

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The main objective is to compare the mitochondrial dynamic between patients operated for aneurysm of ascending aorta or type A aortic dissection (AAD) or control group

Detailed Description

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In an aortic aneurysm process, the alteration of the extracellular matrix (ECM) as well as the apoptosis of the smooth muscle cells are due to inflammatory phenomena and oxydative stress, involving mitochondria which has a key place within cells.

Mitochondrial fusion and fission constitute mitochondrial dynamic and are involved in the mechanisms described above.

The alteration of mitochondrial dynamics has been demonstrated in many pathologies, in particular neurological, cancer and cardiovascular disease and generally occurs in favor of fission.

In a mouse model (FASEB J, 2021, Robert P ), the role of mitochondrial fusion has been demostrated as a protective factor against hypertension in resistance arteries and a deletion of OPA1 (optic Atrophy 1) fusion protein may lead to aneurysm until aortic dissection. The results of this experimental study suggest a role of the alteration of mitochondrial dynamic in the development of aneurysm and aortic dissection.

Conditions

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Aortic Aneurysm and Dissection

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Aneurysm and Dissection of Ascending Thoracic Aorta
Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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Aneurysm group

Patients operated for aneurysm of the ascending aorta according the guidelines on the diagnosis and treatment of aortic diseases (European Society of Cardiology - 2014).

Group Type ACTIVE_COMPARATOR

Mitochondrial dynamic analysis in the aorta samples and metabolomic profiling in the aortic diseases

Intervention Type OTHER

* For each patient: a segment of aorta will be sampled and cutted into 4 parts

* 1 fragment placed in a Falcon tube containing DMEM (Dulbecco's Modified Eagle Medium, Thermo Fisher®), temporarily stored at + 4°C, for primary culture of smooth muscle cells will allow analysis of the mitochondrial network.
* 1 fragment placed in a Falcon tube containing Allprotect Tissue Reagent (QIAGEN®), stored at -80°C for gene (RT-PCR) and protein (Western Blot) analysis.
* 2 fragments each placed in dry cryotube stored at - 80°C will be used for metabolomic analysis.
* For each patient, 2 arterial blood samples will be collected before general anaesthesia

* One tube of whole blood stored at -80°C for metabolomic analysis.
* One tube of blood stored at -80°C for plasma cytokines

Type A aortic dissection group

Patients operated for type A aortic dissection according the guidelines on the diagnosis and treatment of aortic diseases (European Society of Cardiology - 2014).

Group Type ACTIVE_COMPARATOR

Mitochondrial dynamic analysis in the aorta samples and metabolomic profiling in the aortic diseases

Intervention Type OTHER

* For each patient: a segment of aorta will be sampled and cutted into 4 parts

* 1 fragment placed in a Falcon tube containing DMEM (Dulbecco's Modified Eagle Medium, Thermo Fisher®), temporarily stored at + 4°C, for primary culture of smooth muscle cells will allow analysis of the mitochondrial network.
* 1 fragment placed in a Falcon tube containing Allprotect Tissue Reagent (QIAGEN®), stored at -80°C for gene (RT-PCR) and protein (Western Blot) analysis.
* 2 fragments each placed in dry cryotube stored at - 80°C will be used for metabolomic analysis.
* For each patient, 2 arterial blood samples will be collected before general anaesthesia

* One tube of whole blood stored at -80°C for metabolomic analysis.
* One tube of blood stored at -80°C for plasma cytokines

Control group

Patients without aortic aneurysm or aortic dissection operated for aortic valve replacement (AVR) and/or coronary artery bypass with a saphenous vein graft for proximal aortic anastomosis to collect the aortic sample. For patients operated for AVR, an aortic sample will be collected before closing the aorta.

Group Type SHAM_COMPARATOR

Mitochondrial dynamic analysis in the aorta samples and metabolomic profiling in the aortic diseases

Intervention Type OTHER

* For each patient: a segment of aorta will be sampled and cutted into 4 parts

* 1 fragment placed in a Falcon tube containing DMEM (Dulbecco's Modified Eagle Medium, Thermo Fisher®), temporarily stored at + 4°C, for primary culture of smooth muscle cells will allow analysis of the mitochondrial network.
* 1 fragment placed in a Falcon tube containing Allprotect Tissue Reagent (QIAGEN®), stored at -80°C for gene (RT-PCR) and protein (Western Blot) analysis.
* 2 fragments each placed in dry cryotube stored at - 80°C will be used for metabolomic analysis.
* For each patient, 2 arterial blood samples will be collected before general anaesthesia

* One tube of whole blood stored at -80°C for metabolomic analysis.
* One tube of blood stored at -80°C for plasma cytokines

Interventions

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Mitochondrial dynamic analysis in the aorta samples and metabolomic profiling in the aortic diseases

* For each patient: a segment of aorta will be sampled and cutted into 4 parts

* 1 fragment placed in a Falcon tube containing DMEM (Dulbecco's Modified Eagle Medium, Thermo Fisher®), temporarily stored at + 4°C, for primary culture of smooth muscle cells will allow analysis of the mitochondrial network.
* 1 fragment placed in a Falcon tube containing Allprotect Tissue Reagent (QIAGEN®), stored at -80°C for gene (RT-PCR) and protein (Western Blot) analysis.
* 2 fragments each placed in dry cryotube stored at - 80°C will be used for metabolomic analysis.
* For each patient, 2 arterial blood samples will be collected before general anaesthesia

* One tube of whole blood stored at -80°C for metabolomic analysis.
* One tube of blood stored at -80°C for plasma cytokines

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Aneurysm aortic group: patients treated for an aneurysm of the ascending thoracic aorta with surgical indication according to the ESC guidelines (2014).
* Aortic dissection group: patients treated for type A acute aortic dissection or intramural hematoma of the ascending thoracic aorta in emergency.
* Control group: patients operated for aortic valve replacement (little aortic sample before closing aortotomy) or coronary artery bypass grafting which the use of a saphenous graft and the performance of a proximal anastomosis on the ascending aorta is planned

Exclusion Criteria

* Patients under 18 years old
* Other acute aortic syndromes (penetrating ulcers, iatrogenic or traumatic dissections)
* Patients treated for aortic valve replacement in the context of infective endocarditis
* Patients treated for emergency aortic valve replacement or coronary bypass surgery\*\*
* Pregnant, parturient and breastfeeding women
* Patients protected by an administrative or judicial measure (curatorship, guardianship)
* Patients receiving psychiatric care under duress
* Adults subject to a legal protection measure.
* Patients whose the samples planned for the study could not be taken;
* Patients in the control group whose tissue sampling will not be performed.
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Fondation de l'Avenir

OTHER

Sponsor Role collaborator

University Hospital, Angers

OTHER_GOV

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Olivier FOUQUET

Angers, , France

Site Status

Countries

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France

References

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Trabado S, Al-Salameh A, Croixmarie V, Masson P, Corruble E, Feve B, Colle R, Ripoll L, Walther B, Boursier-Neyret C, Werner E, Becquemont L, Chanson P. The human plasma-metabolome: Reference values in 800 French healthy volunteers; impact of cholesterol, gender and age. PLoS One. 2017 Mar 9;12(3):e0173615. doi: 10.1371/journal.pone.0173615. eCollection 2017.

Reference Type BACKGROUND
PMID: 28278231 (View on PubMed)

Robert P, Nguyen PMC, Richard A, Grenier C, Chevrollier A, Munier M, Grimaud L, Proux C, Champin T, Lelievre E, Sarzi E, Vessieres E, Henni S, Prunier D, Reynier P, Lenaers G, Fassot C, Henrion D, Loufrani L. Protective role of the mitochondrial fusion protein OPA1 in hypertension. FASEB J. 2021 Jul;35(7):e21678. doi: 10.1096/fj.202000238RRR.

Reference Type RESULT
PMID: 34133045 (View on PubMed)

Toda M, Yamamoto K, Shimizu N, Obi S, Kumagaya S, Igarashi T, Kamiya A, Ando J. Differential gene responses in endothelial cells exposed to a combination of shear stress and cyclic stretch. J Biotechnol. 2008 Jan 20;133(2):239-44. doi: 10.1016/j.jbiotec.2007.08.009. Epub 2007 Aug 9.

Reference Type RESULT
PMID: 17850909 (View on PubMed)

Archer SL. Mitochondrial dynamics--mitochondrial fission and fusion in human diseases. N Engl J Med. 2013 Dec 5;369(23):2236-51. doi: 10.1056/NEJMra1215233. No abstract available.

Reference Type RESULT
PMID: 24304053 (View on PubMed)

Piquereau J, Caffin F, Novotova M, Prola A, Garnier A, Mateo P, Fortin D, Huynh le H, Nicolas V, Alavi MV, Brenner C, Ventura-Clapier R, Veksler V, Joubert F. Down-regulation of OPA1 alters mouse mitochondrial morphology, PTP function, and cardiac adaptation to pressure overload. Cardiovasc Res. 2012 Jun 1;94(3):408-17. doi: 10.1093/cvr/cvs117. Epub 2012 Mar 8.

Reference Type RESULT
PMID: 22406748 (View on PubMed)

Le Page S, Niro M, Fauconnier J, Cellier L, Tamareille S, Gharib A, Chevrollier A, Loufrani L, Grenier C, Kamel R, Sarzi E, Lacampagne A, Ovize M, Henrion D, Reynier P, Lenaers G, Mirebeau-Prunier D, Prunier F. Increase in Cardiac Ischemia-Reperfusion Injuries in Opa1+/- Mouse Model. PLoS One. 2016 Oct 10;11(10):e0164066. doi: 10.1371/journal.pone.0164066. eCollection 2016.

Reference Type RESULT
PMID: 27723783 (View on PubMed)

Other Identifiers

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2022-A00719-34

Identifier Type: -

Identifier Source: org_study_id

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