The Role of Mitochondrial Respiration in the Cardioprotective Capacity of IPC in Diabetic and Non-diabetic Patients

NCT ID: NCT02993484

Last Updated: 2019-06-07

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

COMPLETED

Clinical Phase

NA

Total Enrollment

39 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-12-31

Study Completion Date

2019-02-01

Brief Summary

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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

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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

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Reperfusion Injuries, Myocardial

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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non-diabetic Sham control

Heart tissue obtained from non-diabetic patients undergoing surgery will not receive drugs or ischemia

Group Type EXPERIMENTAL

Sham

Intervention Type OTHER

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.

non-diabetic Ischemia reperfusion

Heart tissue from non-diabetic patients undergoing surgery will not receive drugs but will receive ischemia

Group Type EXPERIMENTAL

Ischemia reperfusion

Intervention Type OTHER

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.

non-diabetic Ischemic preconditioning

Heart tissue from non-diabetic patients undergoing surgery will not receive drugs but will receive short periods of ischemia prior to index ischemia

Group Type EXPERIMENTAL

Ischemic preconditioning

Intervention Type BIOLOGICAL

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.

non-diabetic Dimethyl malonate

Heart tissue from non-diabetic patients undergoing surgery will receive a drug (Dimethyl Malonate) prior to index ischemia

Group Type EXPERIMENTAL

Dimethyl Malonate

Intervention Type DRUG

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.

Diabetic Sham control

Heart tissue obtained from diabetic patients undergoing surgery will not receive drugs or ischemia

Group Type EXPERIMENTAL

Sham

Intervention Type OTHER

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.

Diabetic Ischemia reperfusion

Heart tissue from diabetic patients undergoing surgery will not receive drugs but will receive ischemia

Group Type EXPERIMENTAL

Ischemia reperfusion

Intervention Type OTHER

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.

Diabetic Ischemic preconditioning

Heart tissue from diabetic patients undergoing surgery will not receive drugs but will receive short periods of ischemia prior to index ischemia

Group Type EXPERIMENTAL

Ischemic preconditioning

Intervention Type BIOLOGICAL

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.

Diabetic Dimethyl malonate

Heart tissue from diabetic patients undergoing surgery will receive a drug (Dimethyl Malonate) prior to index ischemia

Group Type EXPERIMENTAL

Dimethyl Malonate

Intervention Type DRUG

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.

Interventions

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Dimethyl Malonate

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.

Intervention Type DRUG

Ischemic preconditioning

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.

Intervention Type BIOLOGICAL

Ischemia reperfusion

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.

Intervention Type OTHER

Sham

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.

Intervention Type OTHER

Other Intervention Names

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Dimethyl Malonate; PubChem Substance ID 24848281

Eligibility Criteria

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Inclusion Criteria

* Patients undergoing CABG or other surgery where extracorporal circulation will be used.

Exclusion Criteria

* raise in ischemic markers within 4 weeks
* ejection fraction \<30
* Atrial fibrilation
* Oral opioid treatment
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Aarhus

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Other Identifiers

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Human A-strips Mitochondria

Identifier Type: -

Identifier Source: org_study_id

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