Cardioprotective and Metabolic Effects of Metformin in Patients With Heart Failure and Diabetes

Cardioprotective and Metabolic Effects of Metformin in Patients With Heart Failure and Diabetes

Sponsors

Lead sponsor: Institute for Clinical and Experimental Medicine

Source Institute for Clinical and Experimental Medicine
Brief Summary

The aim of the study is to evaluate the effect of metformin on myocardial function, insulin resistance and selected metabolic markers in patients with type 2 diabetes and heart failure (HF+DM+) in a cross-over, randomized, placebo controlled trial.

Hypothesis:

Metformin treatment in HF+DM+ group will lead to better myocardial function and load tolerance in comparison to placebo. The degree of improvement will be linked to selected metabolic parameters.

Detailed Description

40 patients with HF and DM without previous diabetes treatment will be randomized into 2 groups (A succession: MET-placebo, B succession: placebo-MET) - stratified randomization with following parameters weighted: HF etiology (ischemic /non-ischemic), diabetes duration, gender, BMI, age, NYHA, smoker/non-smoker). After 3 months the treatment will be switched. All participants will undergo standardized selection of metabolic and cardiovascular tests (hyperinsulinemic euglycemic clamp with indirect calorimetry, measurement of endothelial function, echocardiography, spiroergometry, proton/phosphor MR spectroscopy, adipose tissue biopsy, selected cytokines in plasma and adipose tissue at the beginning and the end of each intervention period (3 times in total).

Overall Status Completed
Start Date November 2012
Completion Date December 2016
Primary Completion Date May 2016
Phase Phase 2/Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
insulin sensitivity at baseline and after 3 months
Secondary Outcome
Measure Time Frame
energy expenditure at baseline and after 3 months
endothelial function at baseline and after 3 months
heart function at baseline and after 3 months
Enrollment 40
Condition
Intervention

Intervention type: Drug

Intervention name: Metformini hydrochloridum (Siofor 1000 tbl, Berlin)

Description: Patients will be randomized into 2 groups (A succession: MET-placebo, B succession: placebo-MET. After 3 months the treatment will be switched. Titration: 500 mg per day(1/2 tbl 1000 mg once a day - in the morning) after a week increase the dose to 1 tbl á 1000 mg after two weeks increase the dose to 2 x tbl 1000 mg (in the morning and in the evening)

Other name: A10BA02 Metformin

Intervention type: Drug

Intervention name: placebo

Description: Patients will be randomized into 2 groups (A succession: MET-placebo, B succession: placebo-MET. After 3 months the treatment will be switched.

Eligibility

Criteria:

Inclusion Criteria:

1. chronic heart failure will be defined by the following criteria (all must be included):

- diagnosis of HF known for at least 6 months

- medical history of hospitalization for cardiac decompensation with need for parenteral therapy for congestion - X-ray findings or swelling of lower extremities

- stable drug therapy at least 1 month

- treatment with diuretics (thiazide or furosemide)

- LVEF below 50%

2. the presence of diabetes will be defined by:

- diagnosis and treatment of type 2 diabetes in the medical history

- screening blood sample:

- the value of HbA1c(according to IFCC)≥ 4.8% + fasting glucose ≥ 7.0 mmol / l in venous plasma or

- the value of HbA1c ≥ 4.8%(according to IFCC) + random blood glucose ≥ 11.1 mmol/l in venous plasma

- or OGTT - blood glucose level at 120 min ≥ 11.1 mmol/l OGTT is indicated just in case of positivity of one of the criteria (fasting glucose + HbA1c or HbA1c + random blood glucose)

- treatment of diabetes - by diet only

- women and men aged 40-70 years

- body mass index (kg/m2) in the range of 20-35

- the range of HbA1c between 4-6,5% IFCC

- signed informed consent

Exclusion Criteria:

1. the planned cardiac intervention during the study that affect the function of the heart (revascularization including PCI, heart surgery, implantation of pacemaker, RF ablation; urgent candidate for OTS

2. metabolic disease, including: 1 type diabetes, decompensated thyreopathy (Note: patients with hypothyroidism and stable substitution (the last 3 months) of normal TSH levels may participate in the study

3. treatment with insulin or PAD one month before the recruitment(patients who were temporarily treated with insulin during hospitalization may participate in the study)

4. pregnancy (positive β-HCG test), breast feeding, trying to become pregnant

5. clinically significant anemia with hemoglobin below 100 g/l

6. renal insufficiency with eGF below 0.7 ml/s

7. atrial fibrillation - present during screening test

8. the presence of other medical condition, which occurs during physical examination, laboratory tests, ECG, including pulmonary, neurological or inflammatory disease, which would be considered by the examiner to distort the consistency of data

Gender: All

Minimum age: 40 Years

Maximum age: 70 Years

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Terezie Pelikanova, Prof., MD Principal Investigator Diabetes Center, Institute of Clinical and Experimental Medicine
Location
facility Diabetes Center, Institute of Clinical and Experimental Medicine
Location Countries

Czechia

Verification Date

March 2018

Responsible Party

Responsible party type: Principal Investigator

Investigator affiliation: Institute for Clinical and Experimental Medicine

Investigator full name: Prof. Terezie Pelikanova

Investigator title: Prof.MUDr.Terezie Pelikanova DrSc.

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: Metformin

Arm group type: Experimental

Description: 500 mg per day(1/2 tbl 1000 mg once a day - in the morning) after a week increase the dose to 1 tbl á 1000 mg after two weeks increase the dose to 2 x tbl 1000 mg (in the morning and in the evening), duration: 3 months

Arm group label: Placebo

Arm group type: Placebo Comparator

Description: 500 mg per day(1/2 tbl 1000 mg once a day - in the morning) after a week increase the dose to 1 tbl á 1000 mg after two weeks increase the dose to 2 x tbl 1000 mg (in the morning and in the evening), duration:3 months

Acronym CARMET
Study Design Info

Allocation: Randomized

Intervention model: Crossover Assignment

Primary purpose: Treatment

Masking: Double (Participant, Investigator)

Source: ClinicalTrials.gov