Liraglutide to Improve corONary Haemodynamics During Exercise streSS
Condition: Ischaemic Heart Disease; Coronary Heart Disease; Chronic Stable Angina
MeSH terms: Heart Diseases; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Angina, Stable; Ischemia
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Liraglutide; Placebo
Intervention type(s): Drug; Other
Intervention description(s): GLP-1 receptor agonist administered via subcutaneous injection; Volume-matched normal saline placebo administered via subcutaneous injection
Other intervention name(s): Victoza
Intervention MeSH terms: Liraglutide
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Keywords: Liraglutide; GLP-1; Ischaemic heart disease; Coronary heart disease; Chronic stable angina