Skip to main content
OpenTrials
Completed

NCT Number: NCT01595789

The Effect of Liraglutide on the Treatment of Coronary Artery Disease and Type 2 Diabetes

The purpose of this study is to investigate the effect of combined glucagon-like-peptide-1 (GLP-1) analogue and metformin therapy on glucose metabolic and cardiovascular endpoints compared to metformin monotherapy in patients with coronary artery disease (CAD) and newly diagnosed type 2 diabetes (T2D).

It is hypothesized that GLP-1 analogue added to backbone therapy of metformin in CAD patients with T2D will improve beta-cell function, left ventricular ejection fraction (LVEF), heart rate variability and lower 24h blood pressure among other selected endpoints.

The present study on CAD patients with newly diagnosed T2D will address these selected endpoints during an investigator initiated, randomized, double blind, crossover, placebo-controlled 12 + 12 weeks intervention study with a 2 week wash-out period.

Completed

Looking for future studies?

Notify Me

Key information

Age range

18 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Copenhagen University Hospital, Bispebjerg

Copenhagen, Bispebjerg, 2400, Denmark

About this study

The total study period for each patient will be 26 weeks (12 plus 12 weeks of intervention with a 2 week wash-out period).

The endpoints will be evaluated at baseline (week 0), at week 12, at week 14 (following 2 weeks of wash-out) and finally at week 26.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Stable CAD documented by one of the following:
  • Previous MI (a minimum of 6 weeks after an acute MI)
  • Previous coronary revascularization
  • CAD confirmed by an abnormal coronary angiography (CAG) or CT-angiography showing stenosis > 50% of any major coronary arteries.
  • Body mass index (BMI) >/= 25,0 kg/m2
  • Age >/= 18 years and </= 85 years
  • Type 2 diabetes diagnosed by one of the following criteria:
  • HbA1c >/= 6.5%
  • HbA1c < 6.5 % and fasting plasma glucose >/= 7.0 mmol/l (confirmed)
  • HbA1c < 6.5 % and a 2 h plasma glucose value during OGTT >/= 11.1 mmol/l

The data for glucose metabolism are accepted provided that they have been obtained within 24 months prior to inclusion of the patient. The glucose metabolic categories are defined by ADA and WHO criteria.

Exclusion criteria

  • Type 1 diabetes mellitus defined as C-peptide < 450 pM
  • Previously diagnosed diabetes mellitus for more than 24 months prior to the screening procedure for this trial, except from gestational diabetes
  • Use of more than 2 types of oral antidiabetic medication and/or use of parenteral antidiabetic medication in the period of 3 months prior to the screening visit. It is accepted that the patient continues his usual antidiabetic medication after the screening visit but antidiabetic medication must be discontinued 2 weeks prior to the baseline visit.
  • Significant heart disease (NYHA > 2; Ejection Fraction < 40% and unstable angina pectoris) and known severe valve disease
  • Documented atrial fibrillation or atrial flutter within 6 weeks previous to the screening. Paroxysmal atrial fibrillation is accepted if sinus rhythm is achieved at the screening.
  • Uncontrolled arterial hypertension (> 180/100 mmHg) at the time of screening
  • Liver (transaminases greater than x 2 the upper normal level) or renal diseases (eGFR < 60 ml/min)
  • Amylase greater than x 3 the upper reference value
  • Any chronic medical condition to unduly increase risk for the potential enrollee as judged by study investigators
  • Dysregulated myxedema or hyperthyroid condition defined by a value of TSH < 0,1 and > 10,0 milli U/L
  • Anemia (< 85% of lower normal limit), leucopenia (< 85% of lower normal limit), or thrombocytopenia (< 85% of lower normal limit)
  • Pregnancy or failure to comply with contraception planning within two years, or breastfeeding
  • Abuse of alcohol or drugs, or any other co-existing condition that would make patients unsuitable to participate in the study, as judged by the investigators
  • Use of immunosuppressive therapy in the preceding 12 months
  • Chronic pancreatitis or previous acute pancreatitis
  • Known or suspected hypersensitivity to trial product(s) or related products
  • Treatment with oral glucocorticoids, calcineurin inhibitors, or dipeptidyl peptidase 4 (DPP4) inhibitors, or other GLP-1 mimetics (e.g. exenatide), which in the Investigator's opinion could interfere with glucose metabolism
  • Cancer (except basal cell skin cancer or squamous cell skin cancer) or any other clinically significant disorder, which in the Investigator's opinion could interfere with the results of the trail
  • Inflammatory bowel disease
  • Previous bowel resection
  • Clinical signs of diabetic gastroparesis
  • Plasma calcium-ion >/= 1,45 mmol/L
  • Plasma calcitonin >/= 50 ng/L
  • Subjects with personal or family history of medullary thyroid carcinoma or a personal history of multiple endocrine neoplasia type 2
  • Refusal to sign informed consent.

Treatment and study plan

liraglutide

Drug

Liraglutide injection pen is administered by the participant once daily by subcutaneous injection. It is given independent of meals. The starting dose is 0.6 mg. After 2 weeks the dose will be increased to 1.2 mg. The dose will be further increased after 4 weeks to 1.8 mg. After a total of 12 weeks of treatment, a wash-out period of 2 weeks follows. Subsequently, the participant will be crossed over to a second period of 12 weeks of treatment with placebo.

Other names: Brand name: Victoza, Active substance: liraglutide, EMA Product number: EMEA/H/C/001026, ATC Code: A10BX07

Placebo

Drug

Volume-matched placebo injection pen is administered by the participant once daily by subcutaneous injection. It is given independent of meals. The starting dose is 0.6 mg volume-matched placebo. After 2 weeks the dose will be increased to 1.2 mg. The dose will be further increased after 4 weeks to 1.8 mg. After a total of 12 weeks of treatment, a wash-out period of 2 weeks follows. Subsequently, the participant will be crossed over to a second period of 12 weeks of treatment with liraglutide.

Primary outcomes

  1. Beta-cell function

    Time frame: after 12 weeks of intervention

    Beta-cell function (disposition index) as measured during an intravenous glucose tolerance test (By Bergman Minimal Model)

  2. LVEF

    Time frame: after 12 weeks of intervention

    Changes in LVEF assessed by dobutamine stress echocardiography

Secondary outcomes

  1. Glucagon, incretin, glucose, NEFA, insulin and C-peptide response during meal test

    Time frame: Baseline (week 0), week 12, week 14, week 26

  2. Insulin sensitivity (Si), acute insulin and C-peptide response to intravenous glucose (AIRg, ACRg), glucose clearance (Kg), glucose effectiveness (Sg) and hepatic extraction of insulin (HEXi)

    Time frame: Baseline (week 0), week 12, week 14, week 26

    Insulin sensitivity (Si), acute insulin and C-peptide response to intravenous glucose (AIRg, ACRg), glucose clearance (Kg), glucose effectiveness (Sg) and hepatic extraction of insulin (HEXi) derived from a standard frequent sampling intravenous glucose tolerance test (FSIGT, Minimal model)

  3. CRP, TNF-alfa and IL-6 in plasma and gene expression of IL6 and TNF-alfa in subcutaneous fat

    Time frame: Baseline (week 0), week 12, week 14, week 26

  4. Non esterified fatty acids (NEFA)

    Time frame: Baseline (week 0), week 12, week 14, week 26

    NEFA during FSIGT by use of NEFA minimal model

  5. Heart rate variability (HRV)

    Time frame: Baseline (week 0), week 12, week 14, week 26

    HRV i.e. SDNN (standard deviation of all normal RR interval) assessed during HOLTER monitoring

  6. Maximal velocity of the myocardium in systole (s´) and in diastole (e´)

    Time frame: Baseline (week 0), week 12, week 14, week 26

    Maximal velocity of the myocardium in systole (s´) and in diastole (e´) during the dobutamine stress test

  7. Changes in exercise tolerance test variables: Total exercise duration (sec), time to limiting angina (sec) and time to 1 mm ST-segment depression (sec)

    Time frame: Baseline (week 0), week 12, week 14, week 26

    Changes in exercise tolerance test variables: Total exercise duration (sec), time to limiting angina (sec) and time to 1 mm ST-segment depression (sec)

  8. ST-depression and ectopic activity

    Time frame: Baseline (week 0), week 12, week 14, week 26

    ST-depression and ectopic activity assessed during 24h HOLTER monitoring

  9. Diurnal blood pressure

    Time frame: Baseline (week 0), week 12, week 14, week 26

  10. Diastolic heart function (E/E*)

    Time frame: Baseline (week 0), week 12, week 14, week 26

    Diastolic heart function (E/E*) in rest and during stress

Sponsors and collaborators

Lead sponsor

Haugaard, Steen Bendix, M.D., DMSc

Indiv

Registry information

Official study title

Adding Liraglutide to the Backbone Therapy of Biguanide in Patients With Coronary Artery Disease and Newly Diagnosed Type-2 Diabetes

Acronym: AddHope2

Important dates

Study start
2012
Primary completion
2014
Study completion
2015
First posted
May 10, 2012
Registry last updated
Mar 7, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.