Cardioprotective Effects of GLP-1 and Their Mechanisms

Angina Pectoris Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02128022
• Other study ID #: P01900
• Status: Completed
• Phase: Phase 1
• First received: April 24, 2014
• Last updated: April 8, 2016
• Start date: July 2014
• Est. completion date: March 2016

Study information

• Verified date: April 2016
• Source: Papworth Hospital NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Angina Pectoris

Intervention

Drug:
• GLP-1 (7-36) amide
Infusion of GLP-1 (7-36) amide 1.2 pmol/Kg/min
• Glibenclamide
Oral Glibenclamide 5mg

Locations

Country	Name	City	State
United Kingdom	Papworth Hospital	Cambridge	Cambridgeshire

Sponsors (1)

Lead Sponsor	Collaborator
Papworth Hospital NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No