Targeting Mitochondrial Fusion and Fission to Prevent Atherosclerosis: Getting the Balance Right

NCT03980548 | Unknown

• 2 other identifiers: 2018/2497SHF/FG651P/2017
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Our preliminary data suggests that pharmacological inhibition of the mitochondrial fission protein, Drp1, reduced atherosclerotic plaque volume and attenuated macrophage accumulation within the plaque in an ApoE-/- mouse model of wire-induced carotid arterial injury. Furthermore, we hypothesize that modulation of mitochondrial morphology and metabolism with Drp1 inhibition prevents atherosclerosis by reducing monocyte activation and migration. In this research proposal, our overall objective will be to investigate the role of Drp1 in human monocytes and macrophages as novel therapeutic targets for preventing atherosclerosis.

Conditions

CAD Patients

Outcome Measures

Primary Outcomes (1)

• "mitochondria-shaping" proteins expression quantified on immunoblotting in patients with atherosclerosis disease.

  Primary outcome analysis for aim 1: The primary endpoint is "mitochondria-shaping" proteins expression quantified on immunoblotting in patients with atherosclerosis disease. The statistical analysis will be performed by 2-tailed student's T-test with the platelet "mitochondria-shaping" proteins expression as the response variable. The primary analyses will be by per protocol analysis and there will also be an intention to treat analysis. Primary outcome analysis for aim 1: The primary endpoint is "mitochondria-shaping" proteins expression quantified on immunoblotting in patients with atherosclerosis disease. The statistical analysis will be performed by 2-tailed student's T-test with the platelet "mitochondria-shaping" proteins expression as the response variable. The primary analyses will be by per protocol analysis and there will also be an intention to treat analysis. The primary endpoint is "mitochondria-shaping" proteins expression quantified on immunoblotting in patients

  2 years

Study Arms (4)

CABG patients

Procedure: CABG

PAD patients

Procedure: CABG

Healthy volunteers

Procedure: CABG

Patients with CAD

Procedure: CABG

Interventions

CABG PROCEDURE

Patients undergoing coronary artery bypass graft and patient presented with ACS undergoing PCI

Also known as: PCI

CABG patients; Healthy volunteers; PAD patients; Patients with CAD

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Study 1 (tissue sample study): * 25 adult patients undergoing coronary artery bypass graft (CABG) surgery: Control tissue will be collected from the left internal mammary artery (LIMA) or radial artery (RA) Atherosclerotic tissue will be collected from aortic root * 25 adult patients undergoing surgical femoral or carotid endarterectomy Endarterectomy atherosclerotic tissue will be collected Study 2 (white blood cell study): * 50 healthy adult volunteers Control blood sample will be collected * 50 adult patients with stable CAD Stable CAD blood sample will be collected * 50 adult patients with unstable CAD Unstable CAD blood sample will be collected

You may qualify if:

• Study 1 (tissue sample study):
• CABG patients
• Patients aged ≥21 years old
• Undergoing elective CABG with aortic valve surgery
• PAD patients:
• Patients aged ≥21 years old
• Undergoing either elective surgical femoral or carotid endarterectomy
• Study 2 (white blood cell study):
• \) Healthy volunteers aged ≥21 years old 2) Patients with stable CAD 3) Patients admitted with ACS treated by PCI in prior 24 hours.

You may not qualify if:

• History of haematological disorders
• Cardiac arrest, Cardiogenic shock, Poor pre-morbid status, Pregnancy

Sponsors & Collaborators

• National Heart Centre Singapore: lead

Study Sites (1)

Hector A. Cabrera-Fuentes

Singapore, 169609, Singapore

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Tissue samples: LIMA or radial or aorta or aortic valve

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Target Duration: 1 Year
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2019
• First Posted: June 10, 2019
• Study Start: October 10, 2018
• Primary Completion: March 31, 2020
• Study Completion: March 31, 2020
• Last Updated: June 10, 2019

Record last verified: 2018-08

Locations

SG (1)