Liraglutide to Improve corONary Haemodynamics During Exercise streSS

What Was Tested

The trial (phase 2) is built around Liraglutide.

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.

It had two arms (groups): Liraglutide (active comparator) and Saline Placebo (placebo comparator).

The registry classes the interventions as drug and other.

More on the Plan

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.

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.

Who Took Part

26 actual participants took part.

It was open to people of any sex aged from 18 years up to 80 years.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: Men and women aged 18-80. Patients must be able to walk confidently on a treadmill. Patients must have a normal resting electrocardiogram (ECG) in sinus rhythm without bundle branch aberration or other conduction disturbance. Patients must have normal left ventricular function.

The full record lists 6 inclusion and 7 exclusion criteria; among the exclusions: an abnormal resting ecg including atrial fibrillation, bundle branch aberration or other conduction disturbance; pre-existing left ventricular systolic dysfunction; pre-existing ischaemic or non-ischaemic cardiomyopathy.

How the Study Was Run

It was run as a randomized, crossover and triple-blind study.

Random assignment meant chance, not the researchers, decided who got Liraglutide and who got the comparison, which limits bias.

In the crossover set-up each of the participants took both Liraglutide and the comparison in turn, acting as their own control.

Neither the participants nor the staff measuring them knew who was on Liraglutide, so expectations could not easily colour the readings.

Those kept unaware of assignments: participant, investigator and outcomes assessor.

It started in 2014-01 with completion listed for 2015-03.

It ran at 1 site in United Kingdom.

What Was Measured

Primary outcome: 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).

It also tracked 7 secondary outcomes, for example Change in total exercise duration, Change in time to 0.1 mV ST-segment depression, Change in recovery time to 0.05 mV ST-segment depression, Evidence of hypoglycaemia, Evidence of renal dysfunction and Evidence of acute pancreatitis.

What This Means in Plain Language

Put simply, this is a phase 2, randomized trial of Liraglutide in 26 people.

Its size is small, so on its own it can only give an early look.

The trial is marked completed; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the Liraglutide compound page, all human trials.