Effect of Liraglutide on Diastolic Dysfunction on Cardiac MRI in Type 2 Diabetes Patients

January 13, 2021 updated by: Annemie Stege Bojer, Rigshospitalet, Denmark

Influence of Liraglutide on Diastolic Cardiac Function and Myocardial Perfusion as Determined by Magnetic Resonance Imaging in Patients With Type 2 Diabetes: a Double-blind Randomized Parallel-group Trial

The purpose of this study is to determine whether liraglutide a GLP-1 analogue are effective in the treatment of diastolic dysfunction in type 2 diabetes patients analyzed by cardiac MRI. Secondary if the treatment has any effect on the perfusion of the heart on a cardiac-MRI.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Aim: To test if treatment with liraglutide a GLP-1 analogue in 18 weeks improves diastolic performance in type 2 diabetes (DM2) patients with diastolic dysfunction, compared to placebo. Furthermore, analyzing cardiac MRI indices of fibrosis and the effect on myocardial perfusion.

The investigators find that especially diastolic dysfunction is of interest, because it is highly overrepresented in DM2 patients and no treatment exists. Glucagon-like peptide 1 analogue could be a possible treatment agent, by increasing the energy level in the myocardium. No previous study has tested the effect of treatment with a glucagon-like peptide 1 analogue on diastolic dysfunction.

Design: A randomised double-blinded placebo-controlled clinical trial. Sample size: 40 patients, 20 in each group. The superior inter-study reproducibility results in considerably lower calculated sample sizes (reductions of 55% to 93%) required by cardiac MR compared with echocardiography to show clinically relevant changes. Power calculations show that only 30 patients are needed form our primary outcome, to allow for dropouts the investigators have chosen to include 40 patients.

Intervention: After randomization, patients will be treated with placebo or liraglutide (up to 1.8 mg s.c. once daily). Total treatment period will be 18 weeks. A cardiac MRI scan and an echocardiography will be preformed at baseline and after 18 weeks.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Copenhagen Ø, Denmark, 210
        • The department of cardiology, Rigshospitalet Denmark

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or female patient fully capable of informed consent
  • Informed consent
  • Age 18-80 years (both years inclusive)
  • T2DM diagnosed at least 3 months prior to visit 0
  • NYHA class I-III at visit 0
  • E/e* ≥ 9 or e* (lateral) ≤10 cm/sec, or both
  • LVEF > 50%
  • LVEDV/BSA < 97 ml/m2
  • Stable on heart medication for 6 weeks prior to randomisation
  • Stable on antidiabetic treatment for 30 days prior to randomisation
  • T2DM must be either treated with one or more oral anti-diabetic drugs or treated with human NPH-insulin or long-acting insulin analogue, alone or in combination with oral drugs

Exclusion Criteria:

  • Lack of consent.
  • NYHA class IV
  • Type 1 diabetes mellitus
  • Incretin-based therapy (GLP-1 receptor agonists; exenatide, liraglutide or other and DPP-IV inhibitors) within 30 days prior to randomisation (visit 1)
  • Glitazon therapy within 30 days prior to randomisation (visit 1)
  • Hypertension with inadequate blood pressure control: Systolic blood pressure > 140 mmHg and/or diastolic blood pressure >85 mmHg*
  • Supine systolic blood pressure <85 mmHg measured at visit 0
  • Significant valvular heart disease
  • Hypertrophic cardiomyopathy, ARVC/D, non-compaction or amyloidosis
  • Myocardial infarction, unstable angina, angina on exertion (≥CCS class 2) or coronary revascularization within 3 months prior to randomisation (visit 1)
  • Hospitalisation due to incompensated heart disease within 30 days to randomisation (visit 1)
  • HbA1c >10% at visit 0
  • eGFR< 60 ml/min/1,73 m2 at visit 0
  • Liver disease with aspartate aminotransferase/alanine aminotransferase >3 times upper limit of normal measured at visit 0**
  • Hypokalaemia (P-potassium <3.5 mmol/L) or hyperkalaemia (P-potassium >5.5 mmol/L) measured at visit 0**
  • Anaemia (haemoglobin <6.5 mmol/L) measured at visit 0**
  • Conditions that may be associated with changes in markers of fibroses or collagen turnover (eg. on-going or active rheumatological disease requiring anti-inflammatory agents, immunosuppression, pulmonary fibrosis, active cancer)
  • Prolonged use (> 2 weeks) of glucocorticoids or NSAIDs within 2 weeks prior to visit 0
  • Women of childbearing potential who are not on acceptable contraception. See below.
  • Pregnant or breastfeeding women
  • Cancer (except basal cell skin cancer or squamous cell skin cancer) unless complete remission for ≥ 5 years
  • Alcohol/drug abuse
  • Chronic or previous acute pancreatitis
  • History of thyroid adenoma or carcinoma
  • Inflammatory bowel disease
  • Clinical signs of diabetic gastroparesis
  • ICD/pacemaker or other contraindications to MRI scan
  • Severe claustrophobia
  • Atrial fibrillation
  • Contraindications to glycopyrrolate: closed-angle glaucoma, prostate hyperplasia, tachycardia, bladder atony, cardia insufficiency, non-congenital pylorus stenosis and gastroparesis
  • Known or suspected hypersensitivity to trial product or related products
  • Current participation in any other clinical intervention trial
  • Receipt of an investigational drug with 30 days prior to visit 0

  • Other concominant disease or treatment that according to investigator's assessment makes the patient unsuitable for participation in the study

    • Measured twice at visit 0. In case of elevation, an ambulatory (24-hour) blood pressure will be performed, and the result of this will be conclusive

      • Measured at visit 0 with the possibility of one repeat analysis within a week, and the last measured value will be conclusive.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Liraglutide arm
Patients will be treated with liraglutide (up to 1.8 mg s.c. once daily). Total treatment period will be 18 weeks.
Drug: Liraglutide
Other Names:
  • Victoza
Placebo Comparator: Placebo arm
Patients will be treated with placebo (up to equal to 1.8 mg drug dose s.c. once daily). Total treatment period will be 18 weeks. The study will be placebo-controlled with placebo as an add-on to conventional diabetes treatment. Thus, no patient will receive a sub-standard treatment.
Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in diastolic properties as assessed by CMR.
Time Frame: Measured in week 18 and compared to baseline.
LA passive emptying fraction (%) (before and after glycopyrolate)
Measured in week 18 and compared to baseline.
Change in diastolic properties as assessed by CMR.
Time Frame: Measured in week 18 and compared to baseline.
LV peak filling rate (ml/s) (before and after glycopyrolate)
Measured in week 18 and compared to baseline.

Secondary Outcome Measures

Outcome Measure
Time Frame
MRI indices of myocardial perfusion
Time Frame: Measured in week 18 and compared to baseline.
Measured in week 18 and compared to baseline.
Echocardiographic indices of diastolic dysfunction
Time Frame: Measured in week 18 and compared to baseline.
Measured in week 18 and compared to baseline.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rigshospitalet, Denmark

Collaborators

Novo Nordisk A/S
Slagelse Hospital

Investigators

  • Study Director: Niels Vejlstrup, MD, Med.Sc.D, Rigshospitalet, Denmark

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2016

Primary Completion (Actual)

December 1, 2019

Study Completion (Actual)

December 1, 2019

Study Registration Dates

First Submitted

January 12, 2016

First Submitted That Met QC Criteria

January 13, 2016

First Posted (Estimate)

January 14, 2016

Study Record Updates

Last Update Posted (Actual)

January 14, 2021

Last Update Submitted That Met QC Criteria

January 13, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2015-000410-22 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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