CAD PatientsMITOFFANCT03980548
Targeting Mitochondrial Fusion and Fission to Prevent Atherosclerosis: Getting the Balance Right
An observational study of CAD Patients, run by National Heart Centre Singapore at 1 site in Singapore.
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. Read more about this study
- Who is it for?
- Ages 21 years and olderHealthy volunteers can take part
- Conditions the study is for
- CAD Patients
- What is being tested?
- CABG
- Type of treatment
- Surgery or procedure
- How many people
- 200 participants
- Where
- 1 siteSingapore
- Study dates
- 10 Oct 2018to 31 Mar 2020
- How long will I take part?
- 1 Year
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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
Who may be able to join
- 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
Show all 10Show fewer
- 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.
- -
Who cannot join
- 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.
- History of haematological disorders
- Cardiac arrest, Cardiogenic shock, Poor pre-morbid status, Pregnancy
Trial locations and contacts
1 site in 1 country.
Singapore1 site, 1 recruiting
- Recruiting
Hector A. Cabrera-Fuentes
Singapore, 169609
Tan Mui Teng, 67042297, tan.mui.teng@nhcs.com.sg
About this study
Official title: Targeting Mitochondrial Fusion and Fission to Prevent Atherosclerosis: Getting the Balance Right - MITOFFA
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.
Read the detailed 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.
- Conditions
- CAD Patients
- Being tested
- CABG
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CABGProcedure or surgery
Also called PCI
Patients undergoing coronary artery bypass graft and patient presented with ACS undergoing PCI
| Study group | Role | What they receive |
|---|---|---|
| CABG patients | Not described Receives: Procedure: CABG | |
| PAD patients | Not described Receives: Procedure: CABG | |
| Healthy volunteers | Not described Receives: Procedure: CABG | |
| Patients with CAD | Not described Receives: Procedure: CABG |
What is being measured
The primary outcome is the main question the study is designed to answer.
"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
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2019
- Study start10 Oct 2018
- Primary completion31 Mar 2020 (estimated)
- Study completion31 Mar 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CAD PatientsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Other
- Enrolment
- 200 participants (estimated)
- Target duration
- 1 Year
Sponsor and investigators
- Lead sponsor
- National Heart Centre Singapore
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03980548
- Sponsor's protocol ID
- 2018/2497
- Other IDs
- SHF/FG651P/2017
- Acronym
- MITOFFA
- Status last verified
- Aug 2018
- First submitted
- 6 Jun 2019
- Last updated
- 10 Jun 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting Mitochondrial Fusion and Fission to Prevent Atherosclerosis: Getting the Balance Right - MITOFFA
- ClinicalTrials.gov ID
- NCT03980548
- Acronym / sponsor ID
- MITOFFA / 2018/2497
- Conditions
- CAD Patients
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- National Heart Centre SingaporeUniversity, hospital or other
- Study start
- 10 Oct 2018 (actual)
- Primary completion
- 31 Mar 2020 (estimated)
- Study completion
- 31 Mar 2020 (estimated)
- First posted
- 10 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Observational model
- Other
- Time perspective
- Other
- Target follow-up
- 1 Year
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| CABG patients | – | Procedure: CABG |
| PAD patients | – | Procedure: CABG |
| Healthy volunteers | – | Procedure: CABG |
| Patients with CAD | – | Procedure: CABG |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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
Key inclusion criteria (10 listed)
- CABG patients
- Patients aged ≥21 years old
- Undergoing elective CABG with aortic valve surgery
- Patients aged ≥21 years old
- Undergoing either elective surgical femoral or carotid endarterectomy
Key exclusion criteria (3 listed)
- 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.
- History of haematological disorders
- Cardiac arrest, Cardiogenic shock, Poor pre-morbid status, Pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CABGAlso: PCIPatients undergoing coronary artery bypass graft and patient presented with ACS undergoing PCI | Procedure or surgery | CABG patients, Healthy volunteers, PAD patients, Patients with CAD |
Primary outcome
"mitochondria-shaping" proteins expression quantified on immunoblotting in patients with atherosclerosis disease.
Time frame: 2 years
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2019.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of CAD Patients, run by National Heart Centre Singapore at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
"mitochondria-shaping" proteins expression quantified on immunoblotting in patients with atherosclerosis disease. (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2019.