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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2012 by Institute for Clinical and Experimental Medicine
Sponsor:
Information provided by (Responsible Party):
Prof. Terezie Pelikanova, Institute for Clinical and Experimental Medicine
ClinicalTrials.gov Identifier:
NCT01690091
First received: March 12, 2012
Last updated: October 6, 2013
Last verified: September 2012
  Purpose

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.


Condition Intervention Phase
Insulin Resistance
Chronic Heart Failure
Drug: Metformini hydrochloridum (Siofor 1000 tbl, Berlin)
Drug: placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Cardioprotective and Metabolic Effects of Metformin in Patients With Heart Failure and Diabetes

Resource links provided by NLM:


Further study details as provided by Institute for Clinical and Experimental Medicine:

Primary Outcome Measures:
  • insulin sensitivity [ Time Frame: at baseline and after 3 months ] [ Designated as safety issue: Yes ]
    change of glucose disposal during clamp


Secondary Outcome Measures:
  • energy expenditure [ Time Frame: at baseline and after 3 months ] [ Designated as safety issue: Yes ]
    change of energy expenditure measured by indirect calorimetry

  • endothelial function [ Time Frame: at baseline and after 3 months ] [ Designated as safety issue: Yes ]
    change in digital pulse amplitude tonometry

  • heart function [ Time Frame: at baseline and after 3 months ] [ Designated as safety issue: Yes ]
    change measured by echocardiography and spiroergometry


Estimated Enrollment: 40
Study Start Date: November 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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)
Drug: 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)

Other Name: A10BA02 Metformin
Drug: placebo
Placebo Comparator: 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)
Drug: 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)

Other Name: A10BA02 Metformin
Drug: placebo

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).

  Eligibility

Ages Eligible for Study:   40 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01690091

Contacts
Contact: Terezie Pelikanova, Prof., MD +420 261 364 100 terezie.pelikanova@medicon.cz

Locations
Czech Republic
Diabetes Center, Institute of Clinical and Experimental Medicine Recruiting
Prague, Czech Republic
Sponsors and Collaborators
Institute for Clinical and Experimental Medicine
Investigators
Principal Investigator: Terezie Pelikanova, Prof., MD Diabetes Center, Institute of Clinical and Experimental Medicine
  More Information

No publications provided

Responsible Party: Prof. Terezie Pelikanova, Prof.MUDr.Terezie Pelikanova DrSc., Institute for Clinical and Experimental Medicine
ClinicalTrials.gov Identifier: NCT01690091     History of Changes
Other Study ID Numbers: NT13034
Study First Received: March 12, 2012
Last Updated: October 6, 2013
Health Authority: Czech Republic: Ethics Committee

Keywords provided by Institute for Clinical and Experimental Medicine:
chronic heart failure
type 2 diabetes
metformin
insulin resistance

Additional relevant MeSH terms:
Heart Failure
Insulin Resistance
Cardiovascular Diseases
Glucose Metabolism Disorders
Heart Diseases
Hyperinsulinism
Metabolic Diseases
Metformin
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 20, 2014