A Phase 2 interventional study of Liraglutide and Placebo in Ischaemic Heart Disease, Coronary Heart Disease and Chronic Stable Angina, sponsored by King's College London. Completed at 1 site in United Kingdom. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2015-05-20.
Sponsored by King's College London · Phase 2 and Interventional
A single-centre double-blind placebo-controlled crossover randomised controlled trial to determine the physiological basis of glucagon-like peptide-1 receptor activation on exercise haemodynamics, as manifest through specific electrophysiological parameters measured by serial exercise stress testing, in those patients with reversible myocardial ischaemia and obstructive coronary artery disease confirmed by a baseline exercise test and coronary angiography respectively.
Glucagon-like peptide-1 (GLP-1), an endogenous incretin hormone, is secreted by the gut in response to enteral nutrition and is responsible primarily for normal glucose homeostasis. There is a defective incretin effect in Type II diabetes mellitus such that meal-stimulated GLP-1 secretion is markedly impaired. However, a continuous infusion of exogenous GLP-1 can result in near normal insulin responses to a glucose load, suggesting preservation of insulinotropic activity. Liraglutide, a synthetic analogue that shares 97% structural homology to native GLP-1, is now a guideline-mandated antidiabetic therapy given as a once-daily subcutaneous injection.
Evidence emerging from animal and latterly human studies suggest GLP-1, independent of its effect on glycemic control and weight loss, may protect the heart from myocardial ischaemia/reperfusion injury and could potentially modulate the metabolic and haemodynamic outcomes of patients with coronary artery disease and left ventricular systolic dysfunction.
The investigators aim to determine whether chronic GLP-1 receptor occupancy has any effect on exercise haemodynamics in patients with known chronic stable angina, evidence of reversible ischaemia on exercise stress testing and angiographic evidence of obstructive coronary artery disease. Each study participant will be randomised to enter either a GLP-1 treatment arm or volume-matched saline placebo arm. Those randomised to GLP-1 will have a week's run-in phase with 0.6 mg Liraglutide followed by a week's course of 1.2 mg Liraglutide. At the end of Week 2, patients in the treatment arm will have their first exercise tolerance test (ETT). They will then be up-titrated to high dose 1.8 mg Liraglutide for another week before performing a Week 3 ETT. Patients in the placebo arm will have matched volume saline injections for the first two weeks before the Week 2 ETT and then another week of saline injections before the Week 3 ETT.
At the end of Week 3 patients will crossover so that those in the GLP-1 treatment arm cross to the placebo arm and vice versa. By incorporating a run-in phase followed by a step-wise increase in Liraglutide therapy over a 3-week period the investigators aim to minimise the occurrence of adverse reactions and also hope to observe a dose-response effect on exercise haemodynamics. The crossover design will allow study participants to effectively act as their own controls.
3,639 studies on the registry are indexed under Heart Diseases; 461 are open to participants now.
This study's enrollment of 26 is below the median of 100 across 1,778 interventional studies indexed under Heart Diseases.
Browse Heart Diseases studies →King's College London is the lead sponsor of 506 studies on the registry; 125 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Week 1 Run-In Phase = 0.6 mg (0.1 ml) Liraglutide once daily via subcutaneous injection Week 2 Low-Dose Phase = 1.2 mg (0.2 ml) Liraglutide once daily via subcutaneous injection Week 3 High-Dose Phase = 1.8 mg (0.3 ml) Liraglutide once daily via subcutaneous injection
Drug: Liraglutide
Week 1 Run-In Phase = 0.1 ml normal saline once daily via subcutaneous injection Week 2 Low-Dose Phase = 0.2 ml normal saline once daily via subcutaneous injection Week 3 High-Dose Phase = 0.3 ml normal saline once daily via subcutaneous injection
Other: Placebo
GLP-1 receptor agonist administered via subcutaneous injection
Also known as: Victoza
Volume-matched normal saline placebo administered via subcutaneous injection
Change in rate pressure product at 0.1 mV ST-segment depression
Time frame: Following consecutive exercise treadmill tests performed at Week 2, Week3, Week 5 and Week 6 of a 6-week study protocol
Change in degree of ST-segment depression at peak exercise
Time frame: Following consecutive exercise treadmill tests performed at Week 2, Week3, Week 5 and Week 6 of a 6-week study protocol
Change in total exercise duration
Time frame: Following consecutive exercise treadmill tests performed at Week 2, Week3, Week 5 and Week 6 of a 6-week study protocol
Change in time to 0.1 mV ST-segment depression
Time frame: Following consecutive exercise treadmill tests performed at Week 2, Week3, Week 5 and Week 6 of a 6-week study protocol
Change in recovery time to 0.05 mV ST-segment depression
Time frame: Following consecutive exercise treadmill tests performed at Week 2, Week3, Week 5 and Week 6 of a 6-week study protocol
Evidence of hypoglycaemia
Monitored via twice daily home glucose monitoring and once weekly random serum glucose measurements
Time frame: During 6-week study protocol
Evidence of renal dysfunction
Monitored via once weekly measurement of serum creatinine, electrolytes and estimated glomerular filtration rate
Time frame: During 6-week study protocol
Evidence of acute pancreatitis
Monitored via once weekly measurement of serum amylase along with telephone and once weekly face-to-face interviews
Time frame: During 6-week study protocol
Change in time to maximum ST-segment depression
Time frame: Following consecutive exercise treadmill tests performed at Week 2, Week3, Week 5 and Week 6 of a 6-week study protocol
This study is completed, as verified in May 2015. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
King's College London