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

Primary Purpose

Insulin Resistance, Chronic Heart Failure

Status
Completed
Phase
Phase 2
Locations
Czechia
Study Type
Interventional
Intervention
Metformini hydrochloridum (Siofor 1000 tbl, Berlin)
placebo
Sponsored by
Institute for Clinical and Experimental Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Insulin Resistance focused on measuring chronic heart failure, type 2 diabetes, metformin, insulin resistance

Eligibility Criteria

40 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Diabetes Center, Institute of Clinical and Experimental Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Metformin

Placebo

Arm 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

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

Outcomes

Primary Outcome Measures

insulin sensitivity
change of glucose disposal during clamp

Secondary Outcome Measures

energy expenditure
change of energy expenditure measured by indirect calorimetry
endothelial function
change in digital pulse amplitude tonometry
heart function
change measured by echocardiography and spiroergometry

Full Information

First Posted
March 12, 2012
Last Updated
March 28, 2018
Sponsor
Institute for Clinical and Experimental Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT01690091
Brief Title
Cardioprotective and Metabolic Effects of Metformin in Patients With Heart Failure and Diabetes
Acronym
CARMET
Official Title
Cardioprotective and Metabolic Effects of Metformin in Patients With Heart Failure and Diabetes
Study Type
Interventional

2. Study Status

Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
November 2012 (undefined)
Primary Completion Date
May 2016 (Actual)
Study Completion Date
December 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Institute for Clinical and Experimental Medicine

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Insulin Resistance, Chronic Heart Failure
Keywords
chronic heart failure, type 2 diabetes, metformin, insulin resistance

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Metformin
Arm Type
Experimental
Arm 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 Title
Placebo
Arm Type
Placebo Comparator
Arm 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
Intervention Type
Drug
Intervention Name(s)
Metformini hydrochloridum (Siofor 1000 tbl, Berlin)
Other Intervention Name(s)
A10BA02 Metformin
Intervention 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)
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
Patients will be randomized into 2 groups (A succession: MET-placebo, B succession: placebo-MET. After 3 months the treatment will be switched.
Primary Outcome Measure Information:
Title
insulin sensitivity
Description
change of glucose disposal during clamp
Time Frame
at baseline and after 3 months
Secondary Outcome Measure Information:
Title
energy expenditure
Description
change of energy expenditure measured by indirect calorimetry
Time Frame
at baseline and after 3 months
Title
endothelial function
Description
change in digital pulse amplitude tonometry
Time Frame
at baseline and after 3 months
Title
heart function
Description
change measured by echocardiography and spiroergometry
Time Frame
at baseline and after 3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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% 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: 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 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 treatment with insulin or PAD one month before the recruitment(patients who were temporarily treated with insulin during hospitalization may participate in the study) pregnancy (positive β-HCG test), breast feeding, trying to become pregnant clinically significant anemia with hemoglobin below 100 g/l renal insufficiency with eGF below 0.7 ml/s atrial fibrillation - present during screening test 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Terezie Pelikanova, Prof., MD
Organizational Affiliation
Diabetes Center, Institute of Clinical and Experimental Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Diabetes Center, Institute of Clinical and Experimental Medicine
City
Prague
Country
Czechia

12. IPD Sharing Statement

Learn more about this trial

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

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