NCT02128022

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
32

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Jul 2014

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 24, 2014

Completed
7 days until next milestone

First Posted

Study publicly available on registry

May 1, 2014

Completed
2 months until next milestone

Study Start

First participant enrolled

July 1, 2014

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2016

Completed
Last Updated

April 11, 2016

Status Verified

April 1, 2016

Enrollment Period

1.7 years

First QC Date

April 24, 2014

Last Update Submit

April 8, 2016

Conditions

Angina Pectoris

Keywords

Glucagon-Like Peptide 1Angina PectorisPercutaneous Coronary InterventionIschemic PreconditioningMyocardial Reperfusion Injury

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (3)

  • Left Ventricular Ejection Fraction (%)

    Measured at the time of the procedure

  • Maximal rate of change with time of left ventricular pressure - dP/dt max (mmHg/s)

    Measured at the time of the procedure

  • Minimum rate of change with time of left ventricular pressure - dP/dt min (mmHg/s)

    Measured at the time of procedure

Study Arms (4)

GLP-1 (7-36) amide and Glibenclamide

EXPERIMENTAL

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) amideDrug: Glibenclamide

Glibenclamide alone

EXPERIMENTAL

Glibenclamide 5 mg orally prior to PCI

Drug: Glibenclamide

GLP-1 (7-36) amide

ACTIVE COMPARATOR

GLP-1 (7-36) amide

Drug: GLP-1 (7-36) amide

Saline control

NO INTERVENTION

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

Interventions

GLP-1 (7-36) amideDRUG

Infusion of GLP-1 (7-36) amide 1.2 pmol/Kg/min

GLP-1 (7-36) amideGLP-1 (7-36) amide and Glibenclamide
GlibenclamideDRUG

Oral Glibenclamide 5mg

GLP-1 (7-36) amide and GlibenclamideGlibenclamide alone

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age over 18
  • Able to give informed consent
  • Elective percutaneous intervention for a single vessel coronary stenosis
  • Normal left ventricular function

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Papworth Hospital

Cambridge, Cambridgeshire, CB23 3RE, United Kingdom

Location

Related Publications (1)

  • Giblett JP, Axell RG, White PA, Clarke SJ, McCormick L, Read PA, Reinhold J, Brown AJ, O'Sullivan M, West NE, Dutka DP, Hoole SP. Glucagon-like peptide-1 derived cardioprotection does not utilize a KATP-channel dependent pathway: mechanistic insights from human supply and demand ischemia studies. Cardiovasc Diabetol. 2016 Jul 19;15:99. doi: 10.1186/s12933-016-0416-3.

    PMID: 27431258DERIVED

MeSH Terms

Conditions

Angina PectorisMyocardial Reperfusion Injury

Interventions

glucagon-like peptide 1 (7-36)amideGlyburide

Condition Hierarchy (Ancestors)

Myocardial IschemiaHeart DiseasesCardiovascular DiseasesVascular DiseasesChest PainPainNeurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and SymptomsCardiomyopathiesReperfusion InjuryPostoperative ComplicationsPathologic Processes

Intervention Hierarchy (Ancestors)

Sulfonylurea CompoundsUreaAmidesOrganic ChemicalsSulfonesSulfur Compounds

Study Officials

  • Stephen P Hoole, MD

    Papworth Hospital NHS Foundation Trust

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
FACTORIAL
Sponsor Type
OTHER GOV
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 24, 2014

First Posted

May 1, 2014

Study Start

July 1, 2014

Primary Completion

March 1, 2016

Study Completion

March 1, 2016

Last Updated

April 11, 2016

Record last verified: 2016-04

Locations

GB(1)