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

NCT ID: NCT01690091

Last Updated: 2018-03-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-30
• Study Completion Date: 2016-12-31

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).

Conditions

Insulin Resistance; Chronic Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Metformin

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

Group Type: EXPERIMENTAL

Metformini hydrochloridum (Siofor 1000 tbl, Berlin)

Intervention Type: DRUG

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)

placebo

Intervention Type: DRUG

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

Placebo

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

Group Type: PLACEBO_COMPARATOR

Metformini hydrochloridum (Siofor 1000 tbl, Berlin)

Intervention Type: DRUG

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)

placebo

Intervention Type: DRUG

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

Interventions

Metformini hydrochloridum (Siofor 1000 tbl, Berlin)

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)

Intervention Type: DRUG

placebo

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

Intervention Type: DRUG

Other Intervention Names

A10BA02 Metformin

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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institute for Clinical and Experimental Medicine

OTHER_GOV

Sponsor Role: lead

Responsible Party

Prof. Terezie Pelikanova

Prof.MUDr.Terezie Pelikanova DrSc.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Terezie Pelikanova, Prof., MD

Role: PRINCIPAL_INVESTIGATOR

Diabetes Center, Institute of Clinical and Experimental Medicine

Locations

Diabetes Center, Institute of Clinical and Experimental Medicine

Prague, , Czechia

Countries

Czechia

Other Identifiers

NT13034

Identifier Type: -

Identifier Source: org_study_id