Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors, Ketones, and Cardiovascular Benefit Research Plan
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Change in Phosphocreatine
研究概览
简要总结
The study team will examine the effects of SGLT2i (and SGLT2i-induced increases in plasma ketone concentrations) on skeletal muscle and cardiac ketone uptake, skeletal muscle bioenergetics, cardiopulmonary exercise capacity, and patient-reported functional outcomes.
详细描述
The study team will examine effects of elevated plasma ketones caused by 12-week treatment with an SGLT2i (empagliflozin) treatment in participants with T2DM and HF. The study team will focus on three possible mechanisms of action for these effects and test the following:
(i) Skeletal muscle bioenergetics. Using 31P-MRS, the team will quantitate phosphocreatine [PCr], ATP, inorganic phosphate, phosphodiester, and intracellular pH. With 1H-MRS, and will measure intramyocellular lipid content at rest and ATPmax production after exercise. The team will examine the relationships between phosphorous metabolite concentrations, intramyocellular lipid content, and ATP generation before and after 12 weeks of SGLT2 inhibition.
(ii) Cardiopulmonary functional capacity.
(iii) Improvements in Patient-Reported Outcomes (PRO). The Patient-Reported Outcomes Measure Information System (PROMIS) Item Bank v2.0 - Physical Function - Short Form 20a will be used to evaluate self-reported physical function and well-being. This tool is a well-developed and validated method to obtain patient self-reported parameters of health in adults.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
盲法说明
Participants and investigators will be blinded to the randomization.
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Type 2 Diabetes Mellitus
- •Class II-III New York Heart Association (NYHA) heart failure and reduced ejection fraction (EF) <50%
- •Age 18-80 years
- •BMI 23-38 kg/m2
- •Glycated hemoglobin (HbA1c) 5.5-10%
- •Blood Pressure (BP) ≤ 145/85 mmHg
- •Estimated glomerular filtration rate (eGFR) ≥30 ml/min•1.73 m2
- •Stable dose of guideline-directed medications for heart failure and Diabetes
- •Stable body weight (±4 pounds) over the last 3 months
- •Does not suffer from severe claustrophobia
- •No contraindication for MRI (metal plates, screws, shrapnel, pins, or cardiac pacemaker)
排除标准
- •Subjects treated with an SGLT2 inhibitor, a glucagon-like peptide-1 receptor agonist (GLP-1 RA) or pioglitazone
- •Pregnancy, lactation or plans to become pregnant
- •Allergy/sensitivity to study drugs or their ingredients
- •Current drug or alcohol use or dependence
- •Inability or unwillingness of individual or legal guardian/representative to give written informed consent
研究组 & 干预措施
Placebo group
Subjects will be randomized to receive the empagliflozin placebo for 3 months
干预措施: Placebo (Drug)
Empagliflozin Group
Subjects will be randomized 2:1 to receive empagliflozin, 25mg/day for 3 months
干预措施: Empagliflozin 25 MG (Drug)
结局指标
主要结局
Change in Phosphocreatine
时间窗: Baseline to 3 months
A measure of phosphocreatine change from baseline to study end
ATPmax production
时间窗: Baseline to 3 months
Exercise induced ATPmax production change
Change in Adenosine Triphosphate (ATP)
时间窗: Baseline to 3 months
A measure of ATP change from baseline to study end
Change in Inorganic Phosphate
时间窗: Baseline to 3 months
A measure of inorganic phosphate change from baseline to study end
Change in Phosphodiester
时间窗: Baseline to 3 months
A measure of phosphodiester change from baseline to study end
次要结局
- Plasma Beta-hydroxybutyrate (β-OH-B)(Baseline to 3 months)
- Acetoacetate concentrations(Baseline to 3 months)
- Cardiopulmonary Function(Baseline to 3 months)
- 6 minute walk test(Baseline to 3 months)
- Patient-Reported Outcomes Measure Information System (PROMIS)(Baseline to 3 months)