Reperfusion Injuries, MyocardialNCT02993484
The Role of Mitochondrial Respiration in the Cardioprotective Capacity of IPC in Diabetic and Non-diabetic Patients
A study testing Dimethyl Malonate, Ischemic preconditioning and Ischemia reperfusion in people with Reperfusion Injuries, Myocardial, run by University of Aarhus.
Trial summary
The overall aim of this study is to examine the role of mitochondrial respiration in human diabetic tissue before and after ischemia. Furthermore we will examine the ability of ischemic preconditioning (IPC) to preserve the mitochondrial function and hemodynamic performance of both non-diabetic and diabetic fibers… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Reperfusion Injuries, Myocardial
- What is being tested?
- Dimethyl Malonate, Ischemic preconditioning and Ischemia reperfusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 39 participants
- Where
- No sites listed yet
- Study dates
- Dec 2016to 1 Feb 2019
- Phase
- Interventional
- 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 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients undergoing CABG or other surgery where extracorporal circulation will be used.
Who cannot join
- raise in ischemic markers within 4 weeks
- ejection fraction <30
- Atrial fibrilation
- Oral opioid treatment
About this study
The overall aim of this study is to examine the role of mitochondrial respiration in human diabetic tissue before and after ischemia. Furthermore we will examine the ability of ischemic preconditioning (IPC) to preserve the mitochondrial function and hemodynamic performance of both non-diabetic and diabetic fibers after ischemia. To increase our understanding on the metabolic changes during ischemia in both non-diabetic and diabetic tissue we will use Dimethyl Malonate and examine the impact of this blockade on post-ischemic mitochondrial respiration.
Read the detailed description
20 diabetic and 20 non-diabetic patients undergoing elective CABG surgery or other heart surgery where extracorporal circulation is used will be included in the study. The patiens will not be given any treatment prior to the operation. During the cardiac surgery a small sample of the heart is routinely removed when the patient is connection to the heart-lung machine. From this tissue sample it is possible to isolate muscle trabeculae which will be used in an atrial strip model and randomized to one of four types of treatment. Simultaneously with the isolation of the trabeculae, a fifth trabecular will be used to assess mitochondrial respiration at baseline. Group 1 will serve as a sham control, group 2 will serve as ischemic control and receive an extended period of hypoxia, Group 3 will be treated with ischemic preconditioning, where short periods of non lethal lack of oxygen will be given directly to the tissue (after removal from the patient) prior to the extended period of hypoxia, Group 4 will receive dimethyl malonate prior to the prolonged hypoxia.
- Conditions
- Reperfusion Injuries, Myocardial
- Being tested
- Dimethyl Malonate, Ischemic preconditioning, Ischemia reperfusion, Sham
- Medical subject headings
- Myocardial Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dimethyl MalonateDrug
Also called Dimethyl Malonate; PubChem Substance ID 24848281
Heart tissue will be obtained from patients undergoing heart surgery. The tissue will be used to test the properties of ischemia and different cardioprotective interventions.
Ischemic preconditioningBiological
Heart tissue will be obtained from patients undergoing heart surgery. The tissue will be used to test the properties of ischemia and different cardioprotective interventions.
Ischemia reperfusionOther
Heart tissue will be obtained from patients undergoing heart surgery. The tissue will be used to test the properties of ischemia and different cardioprotective interventions.
ShamOther
Heart tissue will be obtained from patients undergoing heart surgery. The tissue will be used to test the properties of ischemia and different cardioprotective interventions.
| Study group | Role | What they receive |
|---|---|---|
| non-diabetic Sham control | Experimental | Heart tissue obtained from non-diabetic patients undergoing surgery will not receive drugs or ischemia Receives: Other: Sham |
| non-diabetic Ischemia reperfusion | Experimental | Heart tissue from non-diabetic patients undergoing surgery will not receive drugs but will receive ischemia Receives: Other: Ischemia reperfusion |
| non-diabetic Ischemic preconditioning | Experimental | Heart tissue from non-diabetic patients undergoing surgery will not receive drugs but will receive short periods of ischemia prior to index ischemia Receives: Biological: Ischemic preconditioning |
| non-diabetic Dimethyl malonate | Experimental | Heart tissue from non-diabetic patients undergoing surgery will receive a drug (Dimethyl Malonate) prior to index ischemia Receives: Drug: Dimethyl Malonate |
| Diabetic Sham control | Experimental | Heart tissue obtained from diabetic patients undergoing surgery will not receive drugs or ischemia Receives: Other: Sham |
| Diabetic Ischemia reperfusion | Experimental | Heart tissue from diabetic patients undergoing surgery will not receive drugs but will receive ischemia Receives: Other: Ischemia reperfusion |
| Diabetic Ischemic preconditioning | Experimental | Heart tissue from diabetic patients undergoing surgery will not receive drugs but will receive short periods of ischemia prior to index ischemia Receives: Biological: Ischemic preconditioning |
| Diabetic Dimethyl malonate | Experimental | Heart tissue from diabetic patients undergoing surgery will receive a drug (Dimethyl Malonate) prior to index ischemia Receives: Drug: Dimethyl Malonate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mitochondrial respiration of individual complexes
Mitochondrial respiration of individual complexes will serve as primary outcome and will be examined by oxygraph technique.
Measured: Outcome will be assessed within a year when the inclusion of patients is complete
Secondary outcomes (1)
Hemodynamic performance
Hemodynamic performance will be measured as contractile force of heart fibers before during and after ischemia.
Measured: Outcome will be assessed within a year when the inclusion of patients is complete
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2016 (estimated)
- Study startDec 2016
- Primary completion1 Feb 2019
- Study completion1 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Reperfusion Injuries, MyocardialStudies of the same condition, open and under way.
- More trials run by University of AarhusThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02993484
- Sponsor's protocol ID
- Human A-strips Mitochondria
- Status last verified
- Oct 2018
- First submitted
- 8 Dec 2016
- Last updated
- 7 Jun 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Mitochondrial Respiration in the Cardioprotective Capacity of IPC in Diabetic and Non-diabetic Patients
- ClinicalTrials.gov ID
- NCT02993484
- Acronym / sponsor ID
- Human A-strips Mitochondria
- Conditions
- Reperfusion Injuries, Myocardial
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Study start
- Dec 2016
- Primary completion
- 1 Feb 2019 (actual)
- Study completion
- 1 Feb 2019 (actual)
- First posted
- 15 Dec 2016 (estimated)
- 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.
The overall aim of this study is to examine the role of mitochondrial respiration in human diabetic tissue before and after ischemia. Furthermore we will examine the ability of ischemic preconditioning (IPC) to preserve the mitochondrial function and hemodynamic performance of both non-diabetic and diabetic fibers after ischemia. To increase our understanding on the metabolic changes during ischemia in both non-diabetic and diabetic tissue we will use Dimethyl Malonate and examine the impact of this blockade on post-ischemic mitochondrial respiration.
Detailed description
20 diabetic and 20 non-diabetic patients undergoing elective CABG surgery or other heart surgery where extracorporal circulation is used will be included in the study. The patiens will not be given any treatment prior to the operation. During the cardiac surgery a small sample of the heart is routinely removed when the patient is connection to the heart-lung machine. From this tissue sample it is possible to isolate muscle trabeculae which will be used in an atrial strip model and randomized to one of four types of treatment. Simultaneously with the isolation of the trabeculae, a fifth trabecular will be used to assess mitochondrial respiration at baseline. Group 1 will serve as a sham control, group 2 will serve as ischemic control and receive an extended period of hypoxia, Group 3 will be treated with ischemic preconditioning, where short periods of non lethal lack of oxygen will be given directly to the tissue (after removal from the patient) prior to the extended period of hypoxia, Group 4 will receive dimethyl malonate prior to the prolonged hypoxia.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| non-diabetic Sham control | Experimental | Other: ShamHeart tissue obtained from non-diabetic patients undergoing surgery will not receive drugs or ischemia |
| non-diabetic Ischemia reperfusion | Experimental | Other: Ischemia reperfusionHeart tissue from non-diabetic patients undergoing surgery will not receive drugs but will receive ischemia |
| non-diabetic Ischemic preconditioning | Experimental | Biological: Ischemic preconditioningHeart tissue from non-diabetic patients undergoing surgery will not receive drugs but will receive short periods of ischemia prior to index ischemia |
| non-diabetic Dimethyl malonate | Experimental | Drug: Dimethyl MalonateHeart tissue from non-diabetic patients undergoing surgery will receive a drug (Dimethyl Malonate) prior to index ischemia |
| Diabetic Sham control | Experimental | Other: ShamHeart tissue obtained from diabetic patients undergoing surgery will not receive drugs or ischemia |
| Diabetic Ischemia reperfusion | Experimental | Other: Ischemia reperfusionHeart tissue from diabetic patients undergoing surgery will not receive drugs but will receive ischemia |
| Diabetic Ischemic preconditioning | Experimental | Biological: Ischemic preconditioningHeart tissue from diabetic patients undergoing surgery will not receive drugs but will receive short periods of ischemia prior to index ischemia |
| Diabetic Dimethyl malonate | Experimental | Drug: Dimethyl MalonateHeart tissue from diabetic patients undergoing surgery will receive a drug (Dimethyl Malonate) prior to index ischemia |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients undergoing CABG or other surgery where extracorporal circulation will be used.
Key exclusion criteria (4 listed)
- raise in ischemic markers within 4 weeks
- ejection fraction <30
- Atrial fibrilation
- Oral opioid treatment
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 |
|---|---|---|
| Dimethyl MalonateAlso: Dimethyl Malonate; PubChem Substance ID 24848281Heart tissue will be obtained from patients undergoing heart surgery. The tissue will be used to test the properties of ischemia and different cardioprotective interventions. | Drug | Diabetic Dimethyl malonate, non-diabetic Dimethyl malonate |
| Ischemic preconditioningHeart tissue will be obtained from patients undergoing heart surgery. The tissue will be used to test the properties of ischemia and different cardioprotective interventions. | Biological | Diabetic Ischemic preconditioning, non-diabetic Ischemic preconditioning |
| Ischemia reperfusionHeart tissue will be obtained from patients undergoing heart surgery. The tissue will be used to test the properties of ischemia and different cardioprotective interventions. | Other | Diabetic Ischemia reperfusion, non-diabetic Ischemia reperfusion |
| ShamHeart tissue will be obtained from patients undergoing heart surgery. The tissue will be used to test the properties of ischemia and different cardioprotective interventions. | Other | Diabetic Sham control, non-diabetic Sham control |
Primary outcome
Mitochondrial respiration of individual complexes
Time frame: Outcome will be assessed within a year when the inclusion of patients is complete
Mitochondrial respiration of individual complexes will serve as primary outcome and will be examined by oxygraph technique.
1 secondary outcome
Hemodynamic performance
Time frame: Outcome will be assessed within a year when the inclusion of patients is complete
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2019.
- Individual participant dataSharing planned: No
Related trials for Reperfusion Injuries, Myocardial
RecruitingPhase 2
Prevention of Reperfusion Injury Outcomes Through Effective Cardioprotection Targeting Myocardial Infarction
Myocardial Infarction, Reperfusion Injury
Not yet recruitingPhase 2
Evaluating SGLT2 Inhibitors for the Reduction of No-Reflow Phenomenon in Patients Undergoing PCI
No Reflow Phenomenon, Reperfusion Injuries, Myocardial
RecruitingObservational study
Spectroscopic Assessment of Myocardial Oxygenation Changes in Pediatric Heart Surgery
Myocardial Ischemia, Heart Defects, Congenital
Active, not recruitingPhase 2
Effect of L-Carnitine on Biomarkers of Myocardial Reperfusion Injury in Patients With STEMI
Reperfusion Injury, Myocardial, Myocardial Infarction
Not yet recruitingPhase 2
Combined Antioxidant Therapy for Acute Myocardial Infarction
Acute Myocardial Infarction (AMI), ST Elevation (STEMI) Myocardial Infarction
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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A study testing Dimethyl Malonate, Ischemic preconditioning and Ischemia reperfusion in people with Reperfusion Injuries, Myocardial, run by University of Aarhus.
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 1 inclusion and 4 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: finished, as of the sponsor's last update on 7 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mitochondrial respiration of individual complexes (time frame: Outcome will be assessed within a year when the inclusion of patients is complete). 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 7 Jun 2019.