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Cardioprotective Effects of GLP-1 and Their Mechanisms

Phase 1
Completed
Conditions
Angina Pectoris
Interventions
Registration Number
NCT02128022
Lead Sponsor
Papworth Hospital NHS Foundation Trust
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
32
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
FACTORIAL
Arm && Interventions
GroupInterventionDescription
GLP-1 (7-36) amide and GlibenclamideGLP-1 (7-36) amidePatients will receive 5mg Glibenclamide orally prior to PCI and infusion of GLP-1 (7-36) amide 1.2 pmol/Kg/min during PCI
GLP-1 (7-36) amideGLP-1 (7-36) amideGLP-1 (7-36) amide
Glibenclamide aloneGlibenclamideGlibenclamide 5 mg orally prior to PCI
GLP-1 (7-36) amide and GlibenclamideGlibenclamidePatients will receive 5mg Glibenclamide orally prior to PCI and infusion of GLP-1 (7-36) amide 1.2 pmol/Kg/min during PCI
Primary Outcome Measures
NameTimeMethod
Change in Isovlumetric Relaxation Constant - Tau (ms)Measured at the time of procedure

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.

Secondary Outcome Measures
NameTimeMethod
Left Ventricular Ejection Fraction (%)Measured at the time of the procedure

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.

Maximal rate of change with time of left ventricular pressure - dP/dt max (mmHg/s)Measured at the time of the procedure

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.

Minimum rate of change with time of left ventricular pressure - dP/dt min (mmHg/s)Measured at the time of procedure

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.

Trial Locations

Locations (1)

Papworth Hospital

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Cambridge, Cambridgeshire, United Kingdom

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