Ischaemic Heart DiseasePhase 2LIONESSNCT02315001
Liraglutide to Improve corONary Haemodynamics During Exercise streSS
A Phase 2 study testing Liraglutide in people with Ischaemic Heart Disease and Coronary Heart Disease, run by King's College London at 1 site in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Ischaemic Heart Disease, Coronary Heart Disease, Chronic Stable Angina
- What is being tested?
- Liraglutide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2014to Mar 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women aged 18-80
- Patients with a recent abnormal exercise tolerance test demonstrating >0.1 mV of planar or down-sloping ST-segment depression.
- Patients with known coronary artery disease and angiographic evidence of a >70% stenosis in a main epicardial artery, with or without coronary stenoses elsewhere.
- 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.
Who cannot join
- 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.
- Pre-existing valvular heart disease.
- Inability to safely negotiate an exercise treadmill.
- Type I diabetes mellitus.
- Type II diabetes mellitus taking oral or subcutaneous anti diabetic therapy.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Guy's and St Thomas' NHS Foundation Trust
London, Greater London, SE17EH
About this study
Official title: The Physiological Effects of GLP-1 on Haemodynamics During Exercise in Patients With Ischaemic Heart Disease
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.
Read the 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.
- Being tested
- Liraglutide, Placebo
- Keywords
- Liraglutide, GLP-1, Ischaemic heart disease, Coronary heart disease, Chronic stable angina
- Medical subject headings
- Coronary Artery Disease, Coronary Disease, Angina, Stable
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LiraglutideDrug
Also called Victoza
GLP-1 receptor agonist administered via subcutaneous injection
PlaceboOther
Volume-matched normal saline placebo administered via subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| Liraglutide | Active comparator | 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 Receives: Drug: Liraglutide |
| Saline Placebo | Placebo comparator | 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 Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in rate pressure product at 0.1 mV ST-segment depression
Measured: 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
Measured: Following consecutive exercise treadmill tests performed at Week 2, Week3, Week 5 and Week 6 of a 6-week study protocol
Secondary outcomes (7)
Change in total exercise duration
Measured: 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
Measured: 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
Measured: 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
Measured: During 6-week study protocol
Evidence of renal dysfunction
Monitored via once weekly measurement of serum creatinine, electrolytes and estimated glomerular filtration rate
Measured: 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
Measured: During 6-week study protocol
Change in time to maximum ST-segment depression
Measured: Following consecutive exercise treadmill tests performed at Week 2, Week3, Week 5 and Week 6 of a 6-week study protocol
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2014 (estimated)
- Study startJan 2014
- Primary completionMar 2015
- Study completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Ischaemic Heart DiseaseStudies of the same condition, open and under way.
- More trials run by King's College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- King's College London
- Sponsor type
- University, hospital or other
- Collaborators
- Guy's and St Thomas' NHS Foundation Trust
- Responsible party
- Sponsor
- Investigators
- Michael Marber, PhD FRCP, Principal investigator, King's College LondonSimon Redwood, MD FRCP, Principal investigator, King's College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02315001
- Sponsor's protocol ID
- RJ112/N131
- Other IDs
- FS/11/70/28917
- Acronym
- LIONESS
- Status last verified
- May 2015
- First submitted
- 10 Nov 2014
- Last updated
- 20 May 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Myat A, Arri S, Bhatt DL, Gersh BJ, Redwood SR, Marber MS. Design and rationale for the randomised, double-blinded, placebo-controlled Liraglutide to Improve corONary haemodynamics during Exercise streSS (LIONESS) crossover study. Cardiovasc Diabetol. 2015 Feb 19;14:27. doi: 10.1186/s12933-015-0193-4.
PubMed 25848859Myat A, Redwood SR, Arri S, Gersh BJ, Bhatt DL, Marber MS. Liraglutide to Improve corONary haemodynamics during Exercise streSS (LIONESS): a double-blind randomised placebo-controlled crossover trial. Diabetol Metab Syndr. 2021 Feb 12;13(1):17. doi: 10.1186/s13098-021-00635-6.
PubMed 33579317
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Physiological Effects of GLP-1 on Haemodynamics During Exercise in Patients With Ischaemic Heart Disease
- ClinicalTrials.gov ID
- NCT02315001
- Acronym / sponsor ID
- LIONESS / RJ112/N131
- Keywords
- Liraglutide, GLP-1, Ischaemic heart disease, Coronary heart disease, Chronic stable angina
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- King's College LondonUniversity, hospital or other
- Collaborators
- Guy's and St Thomas' NHS Foundation Trust
- Study start
- Jan 2014
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 11 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Liraglutide | Active comparator | Drug: LiraglutideWeek 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 |
| Saline Placebo | Placebo comparator | Other: PlaceboWeek 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 |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Men and women aged 18-80
- Patients with a recent abnormal exercise tolerance test demonstrating >0.1 mV of planar or down-sloping ST-segment depression.
- Patients with known coronary artery disease and angiographic evidence of a >70% stenosis in a main epicardial artery, with or without coronary stenoses elsewhere.
- 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.
Key exclusion criteria (7 listed)
- 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.
- Pre-existing valvular heart disease.
- Inability to safely negotiate an exercise treadmill.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LiraglutideAlso: VictozaGLP-1 receptor agonist administered via subcutaneous injection | Drug | Liraglutide |
| PlaceboVolume-matched normal saline placebo administered via subcutaneous injection | Other | Saline Placebo |
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
7 secondary outcomes
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
Time frame: During 6-week study protocol
Evidence of renal dysfunction
Time frame: During 6-week study protocol
Evidence of acute pancreatitis
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2015.
- Background: PubMed 25848859Myat A, Arri S, Bhatt DL, Gersh BJ, Redwood SR, Marber MS. Design and rationale for the randomised, double-blinded, placebo-controlled Liraglutide to Improve corONary haemodynamics during Exercise streSS (LIONESS) crossover study. Cardiovasc Diabetol. 2015 Feb 19;14:27. doi: 10.1186/s12933-015-0193-4.
- Derived from this study: PubMed 33579317Myat A, Redwood SR, Arri S, Gersh BJ, Bhatt DL, Marber MS. Liraglutide to Improve corONary haemodynamics during Exercise streSS (LIONESS): a double-blind randomised placebo-controlled crossover trial. Diabetol Metab Syndr. 2021 Feb 12;13(1):17. doi: 10.1186/s13098-021-00635-6.
- Trial rationale and protocolLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Marber, PhD FRCP principal investigator
King's College London
Simon Redwood, MD FRCP principal investigator
King's College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Liraglutide in people with Ischaemic Heart Disease and Coronary Heart Disease, run by King's College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02315001, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2015.