<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01690091</url>
  </required_header>
  <id_info>
    <org_study_id>NT13034</org_study_id>
    <nct_id>NCT01690091</nct_id>
  </id_info>
  <brief_title>Cardioprotective and Metabolic Effects of Metformin in Patients With Heart Failure and Diabetes</brief_title>
  <acronym>CARMET</acronym>
  <official_title>Cardioprotective and Metabolic Effects of Metformin in Patients With Heart Failure and Diabetes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institute for Clinical and Experimental Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Institute for Clinical and Experimental Medicine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of the study is to evaluate the effect of metformin on myocardial function, insulin&#xD;
      resistance and selected metabolic markers in patients with type 2 diabetes and heart failure&#xD;
      (HF+DM+) in a cross-over, randomized, placebo controlled trial.&#xD;
&#xD;
      Hypothesis:&#xD;
&#xD;
      Metformin treatment in HF+DM+ group will lead to better myocardial function and load&#xD;
      tolerance in comparison to placebo. The degree of improvement will be linked to selected&#xD;
      metabolic parameters.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      40 patients with HF and DM without previous diabetes treatment will be randomized into 2&#xD;
      groups (A succession: MET-placebo, B succession: placebo-MET) - stratified randomization with&#xD;
      following parameters weighted: HF etiology (ischemic /non-ischemic), diabetes duration,&#xD;
      gender, BMI, age, NYHA, smoker/non-smoker). After 3 months the treatment will be switched.&#xD;
      All participants will undergo standardized selection of metabolic and cardiovascular tests&#xD;
      (hyperinsulinemic euglycemic clamp with indirect calorimetry, measurement of endothelial&#xD;
      function, echocardiography, spiroergometry, proton/phosphor MR spectroscopy, adipose tissue&#xD;
      biopsy, selected cytokines in plasma and adipose tissue at the beginning and the end of each&#xD;
      intervention period (3 times in total).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">December 2016</completion_date>
  <primary_completion_date type="Actual">May 2016</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>insulin sensitivity</measure>
    <time_frame>at baseline and after 3 months</time_frame>
    <description>change of glucose disposal during clamp</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>energy expenditure</measure>
    <time_frame>at baseline and after 3 months</time_frame>
    <description>change of energy expenditure measured by indirect calorimetry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>endothelial function</measure>
    <time_frame>at baseline and after 3 months</time_frame>
    <description>change in digital pulse amplitude tonometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>heart function</measure>
    <time_frame>at baseline and after 3 months</time_frame>
    <description>change measured by echocardiography and spiroergometry</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Insulin Resistance</condition>
  <condition>Chronic Heart Failure</condition>
  <arm_group>
    <arm_group_label>Metformin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <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</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <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</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformini hydrochloridum (Siofor 1000 tbl, Berlin)</intervention_name>
    <description>Patients will be randomized into 2 groups (A succession: MET-placebo, B succession: placebo-MET. After 3 months the treatment will be switched.&#xD;
Titration:&#xD;
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)</description>
    <arm_group_label>Metformin</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>A10BA02 Metformin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>Patients will be randomized into 2 groups (A succession: MET-placebo, B succession: placebo-MET. After 3 months the treatment will be switched.</description>
    <arm_group_label>Metformin</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. chronic heart failure will be defined by the following criteria (all must be&#xD;
             included):&#xD;
&#xD;
               -  diagnosis of HF known for at least 6 months&#xD;
&#xD;
               -  medical history of hospitalization for cardiac decompensation with need for&#xD;
                  parenteral therapy for congestion - X-ray findings or swelling of lower&#xD;
                  extremities&#xD;
&#xD;
               -  stable drug therapy at least 1 month&#xD;
&#xD;
               -  treatment with diuretics (thiazide or furosemide)&#xD;
&#xD;
               -  LVEF below 50%&#xD;
&#xD;
          2. the presence of diabetes will be defined by:&#xD;
&#xD;
               -  diagnosis and treatment of type 2 diabetes in the medical history&#xD;
&#xD;
               -  screening blood sample:&#xD;
&#xD;
                    -  the value of HbA1c(according to IFCC)≥ 4.8% + fasting glucose ≥ 7.0 mmol / l&#xD;
                       in venous plasma or&#xD;
&#xD;
                    -  the value of HbA1c ≥ 4.8%(according to IFCC) + random blood glucose ≥ 11.1&#xD;
                       mmol/l in venous plasma&#xD;
&#xD;
                    -  or OGTT - blood glucose level at 120 min ≥ 11.1 mmol/l OGTT is indicated&#xD;
                       just in case of positivity of one of the criteria (fasting glucose + HbA1c&#xD;
                       or HbA1c + random blood glucose)&#xD;
&#xD;
               -  treatment of diabetes - by diet only&#xD;
&#xD;
               -  women and men aged 40-70 years&#xD;
&#xD;
               -  body mass index (kg/m2) in the range of 20-35&#xD;
&#xD;
               -  the range of HbA1c between 4-6,5% IFCC&#xD;
&#xD;
               -  signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. the planned cardiac intervention during the study that affect the function of the&#xD;
             heart (revascularization including PCI, heart surgery, implantation of pacemaker, RF&#xD;
             ablation; urgent candidate for OTS&#xD;
&#xD;
          2. metabolic disease, including: 1 type diabetes, decompensated thyreopathy (Note:&#xD;
             patients with hypothyroidism and stable substitution (the last 3 months) of normal TSH&#xD;
             levels may participate in the study&#xD;
&#xD;
          3. treatment with insulin or PAD one month before the recruitment(patients who were&#xD;
             temporarily treated with insulin during hospitalization may participate in the study)&#xD;
&#xD;
          4. pregnancy (positive β-HCG test), breast feeding, trying to become pregnant&#xD;
&#xD;
          5. clinically significant anemia with hemoglobin below 100 g/l&#xD;
&#xD;
          6. renal insufficiency with eGF below 0.7 ml/s&#xD;
&#xD;
          7. atrial fibrillation - present during screening test&#xD;
&#xD;
          8. the presence of other medical condition, which occurs during physical examination,&#xD;
             laboratory tests, ECG, including pulmonary, neurological or inflammatory disease,&#xD;
             which would be considered by the examiner to distort the consistency of data&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Terezie Pelikanova, Prof., MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Diabetes Center, Institute of Clinical and Experimental Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Diabetes Center, Institute of Clinical and Experimental Medicine</name>
      <address>
        <city>Prague</city>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Czechia</country>
  </location_countries>
  <removed_countries>
    <country>Czech Republic</country>
  </removed_countries>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>March 12, 2012</study_first_submitted>
  <study_first_submitted_qc>September 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 21, 2012</study_first_posted>
  <last_update_submitted>March 28, 2018</last_update_submitted>
  <last_update_submitted_qc>March 28, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">March 29, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Institute for Clinical and Experimental Medicine</investigator_affiliation>
    <investigator_full_name>Prof. Terezie Pelikanova</investigator_full_name>
    <investigator_title>Prof.MUDr.Terezie Pelikanova DrSc.</investigator_title>
  </responsible_party>
  <keyword>chronic heart failure</keyword>
  <keyword>type 2 diabetes</keyword>
  <keyword>metformin</keyword>
  <keyword>insulin resistance</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
    <mesh_term>Insulin Resistance</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01690091
org study id: NT13034
nct id: NCT01690091
lead sponsor: 
has dmc: Yes
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.
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).
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: insulin sensitivity
time frame: at baseline and after 3 months
description: change of glucose disposal during clamp
measure: energy expenditure
time frame: at baseline and after 3 months
description: change of energy expenditure measured by indirect calorimetry
measure: endothelial function
time frame: at baseline and after 3 months
description: change in digital pulse amplitude tonometry
measure: heart function
time frame: at baseline and after 3 months
description: change measured by echocardiography and spiroergometry
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
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)
arm group label: Metformin
arm group label: Placebo
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.
arm group label: Metformin
arm group label: Placebo
criteria: 
gender: All
minimum age: 40 Years
maximum age: 70 Years
healthy volunteers: No
last name: Terezie Pelikanova, Prof., MD
role: Principal Investigator
affiliation: Diabetes Center, Institute of Clinical and Experimental Medicine
facility: 
country: Czechia
country: Czech Republic
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.
mesh term: Heart Failure
mesh term: Insulin Resistance
mesh term: Metformin