Cardioprotective Effects of GLP-1 and Their Mechanisms

April 8, 2016 updated by: Papworth Hospital NHS Foundation Trust

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

32

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Cambridgeshire
      • Cambridge, Cambridgeshire, United Kingdom, CB23 3RE
        • Papworth Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Isovlumetric Relaxation Constant - Tau (ms)
Time Frame: 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.
Measured at the time of procedure

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Left Ventricular Ejection Fraction (%)
Time Frame: 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.
Measured at the time of the procedure
Maximal rate of change with time of left ventricular pressure - dP/dt max (mmHg/s)
Time Frame: 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.
Measured at the time of the procedure
Minimum rate of change with time of left ventricular pressure - dP/dt min (mmHg/s)
Time Frame: 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.
Measured at the time of procedure

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Papworth Hospital NHS Foundation Trust

Investigators

  • Principal Investigator: Stephen P Hoole, MD, Papworth Hospital NHS Foundation Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2014

Primary Completion (Actual)

March 1, 2016

Study Completion (Actual)

March 1, 2016

Study Registration Dates

First Submitted

April 24, 2014

First Submitted That Met QC Criteria

April 29, 2014

First Posted (Estimate)

May 1, 2014

Study Record Updates

Last Update Posted (Estimate)

April 11, 2016

Last Update Submitted That Met QC Criteria

April 8, 2016

Last Verified

April 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P01900

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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