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
Overview
- Phase
- Not Applicable
- Intervention
- Placebo oral capsule
- Conditions
- Type2 Diabetes
- Sponsor
- Université de Sherbrooke
- Primary Endpoint
- Change to be observed with canagliflozin on myocardial dietary fatty acid uptake
- Status
- Withdrawn
- Last Updated
- last year
Overview
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.
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. .
Investigators
André Carpentier
tenured professor
Université de Sherbrooke
Eligibility 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;
Arms & Interventions
Treatment 1
placebo oral capsule will be administered once daily, for 2 weeks
Intervention: Placebo oral capsule
Treatment 1
placebo oral capsule will be administered once daily, for 2 weeks
Intervention: PET imaging
Treatment 2
Canagliflozine 100mg once daily, for 2 weeks
Intervention: Canagliflozin 100mg
Treatment 2
Canagliflozine 100mg once daily, for 2 weeks
Intervention: PET imaging
Outcomes
Primary Outcomes
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.
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 Outcomes
- myocardial and liver NEFA uptake(3 months)
- NEFA oxidative rate(3 months)
- plasma NEFA turnover(1 year)