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Impact of a Short-term Treatment With Canagliflozin (Canacardia-HF) (Canacardia)

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ClinicalTrials.gov Identifier: NCT03298009
Recruitment Status : Withdrawn (end of contract negociations)
First Posted : September 29, 2017
Last Update Posted : April 16, 2019
Sponsor:
Collaborator:
Janssen Inc.
Information provided by (Responsible Party):
André Carpentier, Université de Sherbrooke

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Type2 Diabetes Heart Failure Drug: Canagliflozin 100mg Drug: Placebo oral capsule Radiation: PET imaging Not Applicable

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Placebo-controlled, double-blind, randomized crossover 2-week intervention study.
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Basic Science
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
Estimated Study Start Date : November 1, 2017
Estimated Primary Completion Date : November 1, 2018
Estimated Study Completion Date : January 1, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
Placebo Comparator: Treatment 1
placebo oral capsule will be administered once daily, for 2 weeks
Drug: Placebo oral capsule
2-week intervention

Radiation: PET imaging
1 day postprandial metabolic protocol at the end of treatment: CT scan followed by dynamic and pancorporel imaging

Experimental: Treatment 2
Canagliflozine 100mg once daily, for 2 weeks
Drug: Canagliflozin 100mg
2-week intervention
Other Name: Invokana

Radiation: PET imaging
1 day postprandial metabolic protocol at the end of treatment: CT scan followed by dynamic and pancorporel imaging




Primary Outcome Measures :
  1. Change to be observed with canagliflozin on myocardial dietary fatty acid uptake [ Time Frame: 3 months ]

    will be assessed using oral administration of 18-fluoro-thiaheptadecanoic acid ([18F]-FTHA) with sequential dynamic.

    PET/CT scanning.


  2. Change to be observed with canagliflozin on whole-body partitioning. [ Time Frame: 3 months ]
    will be assessed using oral administration of 18-fluoro-thiaheptadecanoic acid ([18F]-FTHA, with static PET/CT scanning


Secondary Outcome Measures :
  1. myocardial and liver NEFA uptake [ Time Frame: 3 months ]
    using PET with [11C]-palmitate

  2. NEFA oxidative rate [ Time Frame: 3 months ]
    using PET with [11C]-acetate

  3. plasma NEFA turnover [ Time Frame: 1 year ]
    using i.v. infusion of [U-13C]-palmitate


Other Outcome Measures:
  1. Insulin sensitivity [ Time Frame: 1 year ]
    will be determined using the HOMA-IR (based on fasting insulin and glucose levels)

  2. Insulin secretion rate [ Time Frame: 1 year ]
    will be assessed using deconvolution of plasma C-peptide with standard Cpeptide kinetic parameters

  3. β-cell function [ Time Frame: 1 year ]
    will be assessed by calculation of the disposition index (DI) that is insulin secretion in response to the ambient insulin

  4. hormonal response [ Time Frame: 1 year ]
    will be determined using a multiplex assay system

  5. Biomarkers [ Time Frame: 1 year ]
    Assays will be performed using the BIOPLEX

  6. body composition [ Time Frame: 3 months ]
    DXA



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HbA1c 7.5 -10.5%;
  • LVEF < 40%;
  • NYHA class 2 or 3;
  • NT pro-BNP level > 600 pg/mL;
  • Being on a stable-dose metformin therapy max 2500 mg/day or other hypoglycemic therapy and RAAS-blocking agents for at least 8 weeks;
  • Being on optimal and stable-doses of heart failure medication including diuretics for at least 4 weeks;

Exclusion Criteria:

  • age <18 yo;
  • NYHA class 4;
  • Treatment with a fibrate or thiazolidinedione;
  • Unstable or advanced renal failure;
  • Unstable or new medical or surgical condition within the past 3 months;
  • Heart failure caused by active inflammatory condition such as sarcoidosis or any form of myocarditis;
  • History of diabetic ketoacidosis;
  • Not on a stable regimen for at least 8 weeks before the screening visit;
  • Female of child-bearing potential who is pregnant, breast feeding or intends to become pregnant or pre-menopausal female with a positive serum pregnancy test at the time of enrollment;
  • Patients post bariatric surgery, or on weight loss medication;
  • Contraindications to metformin, including allergy or intolerance;
  • Hospitalization for heart failure within the 60 days prior to enrollment;
  • Admission for an acute coronary syndrome, percutaneous coronary intervention, or cardiac surgery within the 60 days prior to enrollment;
  • Planned cardiovascular revascularization (percutaneous intervention or surgical) or major cardiac surgery (coronary artery bypass grafting, valve replacement, ventricular assist device, cardiac transplantation, or any other surgery requiring thoracotomy) within the 90 days after enrollment;
  • Patients who are volume depleted based upon physical examination at the time of enrollment;
  • Chronic disabling illness;
  • History of substance abuse.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03298009


Sponsors and Collaborators
Université de Sherbrooke
Janssen Inc.
Investigators
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Principal Investigator: André C. Carpentier Université de Sherbrooke
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Responsible Party: André Carpentier, tenured professor, Université de Sherbrooke
ClinicalTrials.gov Identifier: NCT03298009    
Other Study ID Numbers: 28431754DIA4029
First Posted: September 29, 2017    Key Record Dates
Last Update Posted: April 16, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Heart Failure
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Heart Diseases
Cardiovascular Diseases
Canagliflozin
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs