Cardioprotective Effects of GLP-1 and Their Mechanisms

Study Overview
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Brief Summary
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Ischaemic heart disease is the most common cause of death in the UK. Glucagon-like peptide-1 (GLP-1) has been demonstrated to protect the heart when it is deprived of blood supply (ischaemia). The mechanism for this protection is not clear. Similar protection occurs with ischaemic conditioning of the heart, which is dependent on potassium channel opening. The investigators intend to establish whether GLP-1 mediated protection shares a similar mechanistic pathway. In order to do this the investigators will measures pressure--volume loops generated in the main pumping chamber of the heart at the time of a percutaneous coronary intervention (stenting). Patients will be allocated to GLP-1 alone, GLP-1 with glibenclamide (a potassium channel blocking medication approved for human use), saline control or glibenclamide alone. The investigators hypothesis is that the effect of GLP-1 will be abrogated by use of glibenclamide.

Official Title
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Investigation Into Cardioprotective Effect of Glucagon-like Peptide-1 and it's Mechanism of Action During Myocardial Ischaemia

Conditions
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Angina Pectoris

Intervention / Treatment
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* Drug: GLP-1 (7-36) amide
* Drug: Glibenclamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age over 18 Able to give informed consent Elective percutaneous intervention for a single vessel coronary stenosis Normal left ventricular function Exclusion Criteria: Severe Co-morbidity Type 2 Diabetes Mellitus Nicorandil, Sulphonylureas, DPP4 inhibitors, GLP-1 agonists or Insulin use Women of child bearing age Myocardial infarction in previous three months Previous coronary artery bypass grafts

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GLP-1 (7-36) amide and Glibenclamide<br>Patients will receive 5mg Glibenclamide orally prior to PCI and infusion of GLP-1 (7-36) amide 1.2 pmol/Kg/min during PCI | Drug: GLP-1 (7-36) amide<br>* Infusion of GLP-1 (7-36) amide 1.2 pmol/Kg/min<br>Drug: Glibenclamide<br>* Oral Glibenclamide 5mg<br>|
| Experimental: Glibenclamide alone<br>Glibenclamide 5 mg orally prior to PCI | Drug: Glibenclamide<br>* Oral Glibenclamide 5mg<br>|
| Active Comparator: GLP-1 (7-36) amide<br>GLP-1 (7-36) amide | Drug: GLP-1 (7-36) amide<br>* Infusion of GLP-1 (7-36) amide 1.2 pmol/Kg/min<br>|
| No Intervention: Saline control<br>0.9% saline only (no treatment with GLP-1 (7-36) amide or glibenclamide) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Isovlumetric Relaxation Constant - Tau (ms) | The isovolumetric relaxation constant, Tau, a measure of left ventricular diastolic function, will be measured during the second balloon occlusion of the coronary artery. This will be measured on pressure-volume loop using a conductance catheter. | Measured at the time of procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left Ventricular Ejection Fraction (%) | Ejection fraction, a measure of left ventricular systolic function, will be measured during the second balloon occlusion of the coronary artery. This will be measured on pressure-volume loop using a conductance catheter. | Measured at the time of the procedure | 
| Maximal rate of change with time of left ventricular pressure - dP/dt max (mmHg/s) | dP/dt max, a measure of left ventricular systolic function, will be measured during the second balloon occlusion of the coronary artery. This will be measured on pressure-volume loop using a conductance catheter. | Measured at the time of the procedure | 
| Minimum rate of change with time of left ventricular pressure - dP/dt min (mmHg/s) | dP/dt min, a measure of left ventricular diastolic function, will be measured during the second balloon occlusion of the coronary artery. This will be measured on pressure-volume loop using a conductance catheter. | Measured at the time of procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glucagon-Like Peptide 1, Angina Pectoris, Percutaneous Coronary Intervention, Ischemic Preconditioning, Myocardial Reperfusion Injury