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

CAD Patients Clinical Trial

— MITOFFA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03980548
• Other study ID #: 2018/2497
• Secondary ID: SHF/FG651P/2017
• Status: Recruiting
• Start date: October 10, 2018
• Est. completion date: March 31, 2020

Study information

• Verified date: August 2018
• Source: National Heart Centre Singapore
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

Description:

Study 1 (tissue sample study): To investigate the changes in mitochondrial function and pro-inflammatory markers in human arterial atherosclerotic plaques.

Hypothesis: Macrophages from femoral artery atherosclerotic plaques in patients with peripheral artery disease will display upregulation of mitochondrial fission proteins and features of pro-inflammatory activation.

Study 2 (white blood cell study): To investigate the changes in mitochondrial function and pro-inflammatory markers in white blood cells from patients with stable and unstable coronary artery didease (CAD).

Hypothesis: Monocytes from patients with unstable CAD will display upregulation of Drp1 and features of pro-inflammatory activation, mitochondrial fission, impaired mitochondrial respiratory function, and perturbed metabolism, when compared to monocytes from patients with stable CAD.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: March 31, 2020
• Est. primary completion date: March 31, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years and older

Eligibility

Inclusion Criteria:

Study 1 (tissue sample study):

CABG patients

1. Patients aged =21 years old

2. Undergoing elective CABG with aortic valve surgery

PAD patients:

1. Patients aged =21 years old

2. Undergoing either elective surgical femoral or carotid endarterectomy

Study 2 (white blood cell study):

1) Healthy volunteers aged =21 years old 2) Patients with stable CAD 3) Patients admitted with ACS treated by PCI in prior 24 hours.

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Exclusion Criteria:

1. General exclusion criteria will be a known history of leucopenia, thrombocytopenia, or severe hepatic or renal dysfunction, as well as evidence for inflammatory or malignant disease.

2. History of haematological disorders

3. Cardiac arrest, Cardiogenic shock, Poor pre-morbid status, Pregnancy

Related Conditions & MeSH terms

• Atherosclerosis
• CAD Patients

Intervention

Procedure:
• CABG
Patients undergoing coronary artery bypass graft and patient presented with ACS undergoing PCI

Locations

Country	Name	City	State
Singapore	Hector A. Cabrera-Fuentes	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
National Heart Centre Singapore

Country where clinical trial is conducted

Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	"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