Cardioprotective Effects of GLP-1 and Their Mechanisms

NHS Foundation Trust

Status and phase: Completed; Phase 1

Conditions: Angina Pectoris

Treatments: Drug: Glibenclamide; Drug: GLP-1 (7-36) amide

Study type: Interventional

Funder types: Other

Identifiers

NCT02128022

P01900

Details and patient eligibility

About

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.

Enrollment: 32 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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32 participants in 4 patient groups

GLP-1 (7-36) amide and Glibenclamide

Experimental group

Description:

Patients will receive 5mg Glibenclamide orally prior to PCI and infusion of GLP-1 (7-36) amide 1.2 pmol/Kg/min during PCI

Treatment:

Drug: GLP-1 (7-36) amide

Drug: Glibenclamide

Glibenclamide alone

Experimental group

Description:

Glibenclamide 5 mg orally prior to PCI

Treatment:

Drug: Glibenclamide

GLP-1 (7-36) amide

Active Comparator group

Description:

GLP-1 (7-36) amide

Treatment:

Drug: GLP-1 (7-36) amide

Saline control

No Intervention group

Description:

0.9% saline only (no treatment with GLP-1 (7-36) amide or glibenclamide)