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The Effect of Liraglutide on the Treatment of Coronary Artery Disease and Type 2 Diabetes (AddHope2)

This study is currently recruiting participants.
Verified May 2012 by Haugaard, Steen Bendix, M.D., DMSc
Sponsor:
Information provided by (Responsible Party):
Haugaard, Steen Bendix, M.D., DMSc
ClinicalTrials.gov Identifier:
NCT01595789
First received: May 8, 2012
Last updated: May 10, 2012
Last verified: May 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Coronary Artery Disease
Diabetes Mellitus, Type 2
 Drug: Liraglutide
Drug: Placebo
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Adding Liraglutide to the Backbone Therapy of Biguanide in Patients With Coronary Artery Disease and Newly Diagnosed Type-2 Diabetes

Resource links provided by NLM:

Drug Information available for: Liraglutide
U.S. FDA Resources

Further study details as provided by Haugaard, Steen Bendix, M.D., DMSc:

Primary Outcome Measures:
  • Beta-cell function [ Time Frame: after 12 weeks of intervention ] [ Designated as safety issue: No ]
    Beta-cell function (disposition index) as measured during an intravenous glucose tolerance test (By Bergman Minimal Model)

  • LVEF [ Time Frame: after 12 weeks of intervention ] [ Designated as safety issue: No ]
    Changes in LVEF assessed by dobutamine stress echocardiography


Secondary Outcome Measures:
  • Glucagon, incretin, glucose, NEFA, insulin and C-peptide response during meal test [ Time Frame: Baseline (week 0), week 12, week 14, week 26 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    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)

  • 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 ] [ Designated as safety issue: No ]
  • Non esterified fatty acids (NEFA) [ Time Frame: Baseline (week 0), week 12, week 14, week 26 ] [ Designated as safety issue: No ]
    NEFA during FSIGT by use of NEFA minimal model

  • Heart rate variability (HRV) [ Time Frame: Baseline (week 0), week 12, week 14, week 26 ] [ Designated as safety issue: No ]
    HRV i.e. SDNN (standard deviation of all normal RR interval) assessed during HOLTER monitoring

  • Maximal velocity of the myocardium in systole (s´) and in diastole (e´) [ Time Frame: Baseline (week 0), week 12, week 14, week 26 ] [ Designated as safety issue: No ]
    Maximal velocity of the myocardium in systole (s´) and in diastole (e´) during the dobutamine stress test

  • 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 ] [ Designated as safety issue: No ]
    Changes in exercise tolerance test variables: Total exercise duration (sec), time to limiting angina (sec) and time to 1 mm ST-segment depression (sec)

  • ST-depression and ectopic activity [ Time Frame: Baseline (week 0), week 12, week 14, week 26 ] [ Designated as safety issue: No ]
    ST-depression and ectopic activity assessed during 24h HOLTER monitoring

  • Diurnal blood pressure [ Time Frame: Baseline (week 0), week 12, week 14, week 26 ] [ Designated as safety issue: No ]
  • Diastolic heart function (E/E*) [ Time Frame: Baseline (week 0), week 12, week 14, week 26 ] [ Designated as safety issue: No ]
    Diastolic heart function (E/E*) in rest and during stress


Estimated Enrollment: 40
Study Start Date: May 2012
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo + metformin Drug: Placebo
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.
Other Name: Placebo
Active Comparator: Liraglutide + metformin Drug: Liraglutide
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. Body mass index (BMI) >/= 25,0 kg/m2
  3. Age >/= 18 years and </= 85 years

  4. Type 2 diabetes diagnosed by one of the following criteria:

    • HbA1c >/= 6.5% and </= 8.5%
    • 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 20 weeks before 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
  • HbA1c > 8,5% by the time of the diagnose or at the time of screening
  • Previously diagnosed diabetes mellitus for more than 20 weeks prior to the screening procedure for this trial, except from gestational diabetes
  • Previous use of antidiabetic medication except from use during previous gestational diabetes. Use of oral antidiabetic medication is accepted.
  • 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01595789

Contacts
Contact: Steen B Haugaard, M.D., DMSc +4524628429 or +4531482303 sbhau@dadlnet.dk

Locations
Denmark
Copenhagen University Hospital, Bispebjerg Recruiting
Copenhagen, Bispebjerg, Denmark, 2400
Contact: Ahmad Sajadieh, MD, DMSc     +4531480483     asajadieh@yahoo.com    
Principal Investigator: Ahmad Sajadieh, MD, DMSc            
Sponsors and Collaborators
Haugaard, Steen Bendix, M.D., DMSc
Investigators
Study Director: Steen B Haugaard, M.D., DMSc Copenhagen University Hospital, Amager
Principal Investigator: Ahmad Sajadieh, M.D., DMSc Copenhagen University Hospital, Bispebjerg
  More Information

No publications provided

Responsible Party: Haugaard, Steen Bendix, M.D., DMSc
ClinicalTrials.gov Identifier: NCT01595789     History of Changes
Other Study ID Numbers: BBHAH-2011430, 2011-005405-78
Study First Received: May 8, 2012
Last Updated: May 10, 2012
Health Authority: Denmark: Danish Medicines Agency
Denmark: The Regional Committee on Biomedical Research Ethics
Denmark: Danish Dataprotection Agency
Denmark: The GCP unit at Copenhagen University Hospital

Keywords provided by Haugaard, Steen Bendix, M.D., DMSc:
Coronary Artery Disease
Diabetes Mellitus
Left ventricular ejection fraction
Beta-cell function

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Diabetes Mellitus
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
 Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Glucagon-Like Peptide 1
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 16, 2013