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
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 主要终点
- Change to be observed with canagliflozin on myocardial dietary fatty acid uptake
研究概览
简要总结
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.
详细描述
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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研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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;
排除标准
- •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.
研究组 & 干预措施
Treatment 1
placebo oral capsule will be administered once daily, for 2 weeks
干预措施: Placebo oral capsule (Drug)
Treatment 1
placebo oral capsule will be administered once daily, for 2 weeks
干预措施: PET imaging (Radiation)
Treatment 2
Canagliflozine 100mg once daily, for 2 weeks
干预措施: Canagliflozin 100mg (Drug)
Treatment 2
Canagliflozine 100mg once daily, for 2 weeks
干预措施: PET imaging (Radiation)
结局指标
主要结局
Change to be observed with canagliflozin on myocardial dietary fatty acid uptake
时间窗: 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.
时间窗: 3 months
will be assessed using oral administration of 18-fluoro-thiaheptadecanoic acid (\[18F\]-FTHA, with static PET/CT scanning
次要结局
- myocardial and liver NEFA uptake(3 months)
- NEFA oxidative rate(3 months)
- plasma NEFA turnover(1 year)
研究者
André Carpentier
tenured professor
Université de Sherbrooke