Clinical trial NCT02128022: Cardioprotective Effects of GLP-1 and Their Mechanisms
Official title: Investigation Into Cardioprotective Effect of Glucagon-like Peptide-1 and it's Mechanism of Action During Myocardial Ischaemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Angina Pectoris
Keywords: Glucagon-Like Peptide 1
Angina Pectoris
Percutaneous Coronary Intervention
Ischemic Preconditioning
Myocardial Reperfusion Injury
Lead sponsor: Papworth Hospital NHS Foundation Trust
Sponsor class: OTHER_GOV
First posted: 2014-05-01
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in Isovlumetric Relaxation Constant - Tau (ms)
timeFrame: Measured at the time of procedure
Secondary outcomes:
measure: Left Ventricular Ejection Fraction (%)
timeFrame: Measured at the time of the procedure
measure: Maximal rate of change with time of left ventricular pressure - dP/dt max (mmHg/s)
timeFrame: Measured at the time of the procedure
measure: Minimum rate of change with time of left ventricular pressure - dP/dt min (mmHg/s)
timeFrame: Measured at the time of procedure
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: Papworth Hospital
state: Cambridgeshire
Study officials:
affiliation: Papworth Hospital NHS Foundation Trust
name: Stephen P Hoole, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.