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

NCT ID: NCT03980548

Last Updated: 2019-06-10

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

UNKNOWN

Total Enrollment

200 participants

Study Classification

OBSERVATIONAL

Study Start Date

2018-10-10

Study Completion Date

2020-03-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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CAD Patients

Study Design

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Observational Model Type

OTHER

Study Time Perspective

OTHER

Study Groups

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CABG patients

CABG

Intervention Type PROCEDURE

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

PAD patients

CABG

Intervention Type PROCEDURE

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

Healthy volunteers

CABG

Intervention Type PROCEDURE

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

Patients with CAD

CABG

Intervention Type PROCEDURE

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

Interventions

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CABG

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

Intervention Type PROCEDURE

Other Intervention Names

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PCI

Eligibility Criteria

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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.

\-

Exclusion Criteria

2. History of haematological disorders
3. Cardiac arrest, Cardiogenic shock, Poor pre-morbid status, Pregnancy
Minimum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Heart Centre Singapore

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Hector A. Cabrera-Fuentes

Singapore, , Singapore

Site Status RECRUITING

Countries

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Singapore

Facility Contacts

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Tan Mui Teng

Role: primary

Other Identifiers

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SHF/FG651P/2017

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2018/2497

Identifier Type: -

Identifier Source: org_study_id

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