<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/NCT03298009</url>
  </required_header>
  <id_info>
    <org_study_id>28431754DIA4029</org_study_id>
    <nct_id>NCT03298009</nct_id>
  </id_info>
  <brief_title>Impact of a Short-term Treatment With Canagliflozin (Canacardia-HF)</brief_title>
  <acronym>Canacardia</acronym>
  <official_title>Subclinical Inflammation, Myocardial Function and Fatty Acid Metabolism in Patients With Type 2 Diabetes and Heart Failure: Impact of a Short-term Treatment With Canagliflozin - a Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Université de Sherbrooke</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Janssen Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Université de Sherbrooke</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      It is a mechanistic proof-of-concept study to demonstrate how SGLT-2 inhibitors&#xD;
      (Canagliflozin) may have a beneficial role on cardiac energetic efficiency.&#xD;
&#xD;
      Patients with type 2 diabetes and with HF diagnosed for at least 3 months will be selected.&#xD;
      The participants will be randomized to a double-blind, crossover 2-week placebo vs. Cana 100&#xD;
      mg once daily, an interventional trial with a one-month washout period in between.&#xD;
&#xD;
      At the term of the two-week placebo and canagliflozin treatment periods (visits 2 and 4),&#xD;
      each participant will undergo an identical postprandial metabolic study with positron&#xD;
      emission tomography (PET) and stable isotopic tracer methods.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Non-invasive Positron Emission Tomography (PET) imaging method allows to measure myocardial&#xD;
      uptake and organ-specific partitioning of dietary fatty acids (DFA). It allows to study&#xD;
      kidney, liver, skeletal muscles and adipose tissues DFA utilization, whole body fatty acid&#xD;
      turnover and oxidation rates, myocardial oxidative metabolism and left ventricular (LV)&#xD;
      function that are other likely targets of SGLT-2 inhibitors. Thus, the PET is ideal to verify&#xD;
      the very interesting hypothesis that, increase in liver fatty acid utilization and/or adipose&#xD;
      tissue dietary fatty acid uptake, may lead to reduced cardiac utilization of fatty acids and&#xD;
      improved cardiac energetic efficiency.&#xD;
&#xD;
      .&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    end of contract negociations&#xD;
  </why_stopped>
  <start_date type="Anticipated">November 1, 2017</start_date>
  <completion_date type="Anticipated">January 1, 2019</completion_date>
  <primary_completion_date type="Anticipated">November 1, 2018</primary_completion_date>
  <phase>N/A</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>
    <intervention_model_description>Placebo-controlled, double-blind, randomized crossover 2-week intervention study.</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change to be observed with canagliflozin on myocardial dietary fatty acid uptake</measure>
    <time_frame>3 months</time_frame>
    <description>will be assessed using oral administration of 18-fluoro-thiaheptadecanoic acid ([18F]-FTHA) with sequential dynamic.&#xD;
PET/CT scanning.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change to be observed with canagliflozin on whole-body partitioning.</measure>
    <time_frame>3 months</time_frame>
    <description>will be assessed using oral administration of 18-fluoro-thiaheptadecanoic acid ([18F]-FTHA, with static PET/CT scanning</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>myocardial and liver NEFA uptake</measure>
    <time_frame>3 months</time_frame>
    <description>using PET with [11C]-palmitate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NEFA oxidative rate</measure>
    <time_frame>3 months</time_frame>
    <description>using PET with [11C]-acetate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>plasma NEFA turnover</measure>
    <time_frame>1 year</time_frame>
    <description>using i.v. infusion of [U-13C]-palmitate</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Insulin sensitivity</measure>
    <time_frame>1 year</time_frame>
    <description>will be determined using the HOMA-IR (based on fasting insulin and glucose levels)</description>
  </other_outcome>
  <other_outcome>
    <measure>Insulin secretion rate</measure>
    <time_frame>1 year</time_frame>
    <description>will be assessed using deconvolution of plasma C-peptide with standard Cpeptide kinetic parameters</description>
  </other_outcome>
  <other_outcome>
    <measure>β-cell function</measure>
    <time_frame>1 year</time_frame>
    <description>will be assessed by calculation of the disposition index (DI) that is insulin secretion in response to the ambient insulin</description>
  </other_outcome>
  <other_outcome>
    <measure>hormonal response</measure>
    <time_frame>1 year</time_frame>
    <description>will be determined using a multiplex assay system</description>
  </other_outcome>
  <other_outcome>
    <measure>Biomarkers</measure>
    <time_frame>1 year</time_frame>
    <description>Assays will be performed using the BIOPLEX</description>
  </other_outcome>
  <other_outcome>
    <measure>body composition</measure>
    <time_frame>3 months</time_frame>
    <description>DXA</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Type2 Diabetes</condition>
  <condition>Heart Failure</condition>
  <arm_group>
    <arm_group_label>Treatment 1</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>placebo oral capsule will be administered once daily, for 2 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Canagliflozine 100mg once daily, for 2 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Canagliflozin 100mg</intervention_name>
    <description>2-week intervention</description>
    <arm_group_label>Treatment 2</arm_group_label>
    <other_name>Invokana</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo oral capsule</intervention_name>
    <description>2-week intervention</description>
    <arm_group_label>Treatment 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>PET imaging</intervention_name>
    <description>1 day postprandial metabolic protocol at the end of treatment: CT scan followed by dynamic and pancorporel imaging</description>
    <arm_group_label>Treatment 1</arm_group_label>
    <arm_group_label>Treatment 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  HbA1c 7.5 -10.5%;&#xD;
&#xD;
          -  LVEF &lt; 40%;&#xD;
&#xD;
          -  NYHA class 2 or 3;&#xD;
&#xD;
          -  NT pro-BNP level &gt; 600 pg/mL;&#xD;
&#xD;
          -  Being on a stable-dose metformin therapy max 2500 mg/day or other hypoglycemic therapy&#xD;
             and RAAS-blocking agents for at least 8 weeks;&#xD;
&#xD;
          -  Being on optimal and stable-doses of heart failure medication including diuretics for&#xD;
             at least 4 weeks;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  age &lt;18 yo;&#xD;
&#xD;
          -  NYHA class 4;&#xD;
&#xD;
          -  Treatment with a fibrate or thiazolidinedione;&#xD;
&#xD;
          -  Unstable or advanced renal failure;&#xD;
&#xD;
          -  Unstable or new medical or surgical condition within the past 3 months;&#xD;
&#xD;
          -  Heart failure caused by active inflammatory condition such as sarcoidosis or any form&#xD;
             of myocarditis;&#xD;
&#xD;
          -  History of diabetic ketoacidosis;&#xD;
&#xD;
          -  Not on a stable regimen for at least 8 weeks before the screening visit;&#xD;
&#xD;
          -  Female of child-bearing potential who is pregnant, breast feeding or intends to become&#xD;
             pregnant or pre-menopausal female with a positive serum pregnancy test at the time of&#xD;
             enrollment;&#xD;
&#xD;
          -  Patients post bariatric surgery, or on weight loss medication;&#xD;
&#xD;
          -  Contraindications to metformin, including allergy or intolerance;&#xD;
&#xD;
          -  Hospitalization for heart failure within the 60 days prior to enrollment;&#xD;
&#xD;
          -  Admission for an acute coronary syndrome, percutaneous coronary intervention, or&#xD;
             cardiac surgery within the 60 days prior to enrollment;&#xD;
&#xD;
          -  Planned cardiovascular revascularization (percutaneous intervention or surgical) or&#xD;
             major cardiac surgery (coronary artery bypass grafting, valve replacement, ventricular&#xD;
             assist device, cardiac transplantation, or any other surgery requiring thoracotomy)&#xD;
             within the 90 days after enrollment;&#xD;
&#xD;
          -  Patients who are volume depleted based upon physical examination at the time of&#xD;
             enrollment;&#xD;
&#xD;
          -  Chronic disabling illness;&#xD;
&#xD;
          -  History of substance abuse.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>André C. Carpentier</last_name>
    <role>Principal Investigator</role>
    <affiliation>Université de Sherbrooke</affiliation>
  </overall_official>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>September 26, 2017</study_first_submitted>
  <study_first_submitted_qc>September 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 29, 2017</study_first_posted>
  <last_update_submitted>April 15, 2019</last_update_submitted>
  <last_update_submitted_qc>April 15, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 16, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Université de Sherbrooke</investigator_affiliation>
    <investigator_full_name>André Carpentier</investigator_full_name>
    <investigator_title>tenured professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Canagliflozin</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/NCT03298009
org study id: 28431754DIA4029
nct id: NCT03298009
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
It is a mechanistic proof-of-concept study to demonstrate how SGLT-2 inhibitors
      (Canagliflozin) may have a beneficial role on cardiac energetic efficiency.

      Patients with type 2 diabetes and with HF diagnosed for at least 3 months will be selected.
      The participants will be randomized to a double-blind, crossover 2-week placebo vs. Cana 100
      mg once daily, an interventional trial with a one-month washout period in between.

      At the term of the two-week placebo and canagliflozin treatment periods (visits 2 and 4),
      each participant will undergo an identical postprandial metabolic study with positron
      emission tomography (PET) and stable isotopic tracer methods.
Non-invasive Positron Emission Tomography (PET) imaging method allows to measure myocardial
      uptake and organ-specific partitioning of dietary fatty acids (DFA). It allows to study
      kidney, liver, skeletal muscles and adipose tissues DFA utilization, whole body fatty acid
      turnover and oxidation rates, myocardial oxidative metabolism and left ventricular (LV)
      function that are other likely targets of SGLT-2 inhibitors. Thus, the PET is ideal to verify
      the very interesting hypothesis that, increase in liver fatty acid utilization and/or adipose
      tissue dietary fatty acid uptake, may lead to reduced cardiac utilization of fatty acids and
      improved cardiac energetic efficiency.

      .
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Placebo-controlled, double-blind, randomized crossover 2-week intervention study.
primary purpose: Basic Science
masking: Double (Participant, Outcomes Assessor)
measure: Change to be observed with canagliflozin on myocardial dietary fatty acid uptake
time frame: 3 months
description: will be assessed using oral administration of 18-fluoro-thiaheptadecanoic acid ([18F]-FTHA) with sequential dynamic.
PET/CT scanning.
measure: Change to be observed with canagliflozin on whole-body partitioning.
time frame: 3 months
description: will be assessed using oral administration of 18-fluoro-thiaheptadecanoic acid ([18F]-FTHA, with static PET/CT scanning
measure: myocardial and liver NEFA uptake
time frame: 3 months
description: using PET with [11C]-palmitate
measure: NEFA oxidative rate
time frame: 3 months
description: using PET with [11C]-acetate
measure: plasma NEFA turnover
time frame: 1 year
description: using i.v. infusion of [U-13C]-palmitate
measure: Insulin sensitivity
time frame: 1 year
description: will be determined using the HOMA-IR (based on fasting insulin and glucose levels)
measure: Insulin secretion rate
time frame: 1 year
description: will be assessed using deconvolution of plasma C-peptide with standard Cpeptide kinetic parameters
measure: β-cell function
time frame: 1 year
description: will be assessed by calculation of the disposition index (DI) that is insulin secretion in response to the ambient insulin
measure: hormonal response
time frame: 1 year
description: will be determined using a multiplex assay system
measure: Biomarkers
time frame: 1 year
description: Assays will be performed using the BIOPLEX
measure: body composition
time frame: 3 months
description: DXA
arm group label: Treatment 1
arm group type: Placebo Comparator
description: placebo oral capsule will be administered once daily, for 2 weeks
arm group label: Treatment 2
arm group type: Experimental
description: Canagliflozine 100mg once daily, for 2 weeks
intervention type: Drug
intervention name: Canagliflozin 100mg
description: 2-week intervention
arm group label: Treatment 2
other name: Invokana
intervention type: Drug
intervention name: Placebo oral capsule
description: 2-week intervention
arm group label: Treatment 1
intervention type: Radiation
intervention name: PET imaging
description: 1 day postprandial metabolic protocol at the end of treatment: CT scan followed by dynamic and pancorporel imaging
arm group label: Treatment 1
arm group label: Treatment 2
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: André C. Carpentier
role: Principal Investigator
affiliation: Université de Sherbrooke
responsible party type: Principal Investigator
investigator affiliation: Université de Sherbrooke
investigator full name: André Carpentier
investigator title: tenured professor
mesh term: Heart Failure
mesh term: Diabetes Mellitus, Type 2
mesh term: Canagliflozin