Pioglitazone, Lipotoxicity, and Heart Failure With Preserved Ejection Fraction (HFpEF)
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 78
- 试验地点
- 1
- 主要终点
- Change in Systolic function
研究概览
简要总结
Our goal of the study is to learn the effects of the diabetes medication named Pioglitazone, in type-2 diabetic obese participants with Heart failure. The main question it aims to answer are:
- To demonstrate that impaired mitochondrial function leading to reduced ATP generation plays a key pathophysiologic role in the development of heart failure with preserved ejection fraction (HFpEF) in obese type 2 diabetic (T2D) individuals.
- To demonstrate that pioglitazone, improves diastolic (as well as systolic) function by improving myocardial insulin sensitivity and by reducing both myocardial and epicardial fat content.
详细描述
Either Pioglitazone or Placebo Pioglitazone will be administered during this study in this Type 2 Diabetic population with Heart Failure to examine if there are any beneficial effects on diastolic and systolic function.
Myocardial blood flow (MBF) is measured using a PET scan, then participants will be randomized to pioglitazone or a placebo to examine the effects of the study drug on the effects on the systolic and diastolic function of the heart. In addition, myocardial insulin sensitivity change will be measured as well as myocardial fat content. The ratio of ATP: PCr will also be measured.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Neither the participant nor the investigator knows what treatment is given
入排标准
- 年龄范围
- 30 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Provision of signed and dated informed consent form
- •Stated willingness to comply with all study procedures and availability for the duration of the study
- •Male or female, aged 30-70 years
- •Body Mass Index (BMI) of 27.5-40kg/m²
- •HbA1c of 6.5 to 10%
- •Blood pressure of less than or equal to 145/65mmHg
- •eGFR greater than 45 ml/min/1.73m²
- •Subject must have HFpEF (EF > 50% by ECHO screening)
- •NYHA class II-III heart failure
- •Only T2D patients treated with diet/exercise, metformin, sulfonylurea, metformin/SU, DPP4i or insulin will be studied.
- •For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional [4 weeks] after the end of study participation.
- •For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner.
排除标准
- •Subjects with history of osteoporosis or proliferative diabetic retinopathy
- •Subjects with Heart failure due to restrictive or infiltrative cardiomyopathy, active myocarditis, constrictive pericarditis, severe valvular heart disease, etc. will be excluded
- •Patients with symptomatic coronary artery disease.
- •Subjects with significant change in diuretic management during the month prior to screening (defined by doubling of diuretic dose, or addition of another HF medication).
- •Subjects treated with a GLP-1 RA or thiazolidinedione.
- •Subjects treated with a SGLT2i
- •Pregnancy or lactation
- •Known allergic reactions to components of the study interventions.
- •Any metal plates, parts, screws, shrapnel, pins in body, or cardiac (heart) pacemaker
研究组 & 干预措施
Pioglitazone Administration Group
Pioglitazone 15mg/day titrated to 30 mg/day at week 2 and to 45 mg/day at week 4
干预措施: Pioglitazone (Drug)
Placebo/Control Group
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Systolic function
时间窗: Baseline and 6-months post treatment (approximately 24 weeks)
Measurement of change in systolic function of the heart using cardiac MRI
Change in Diastolic function
时间窗: Baseline and 6-months post treatment (approximately 24 weeks)
Measurement of change in diastolic function of the heart using cardiac MRI
次要结局
- Myocardial fat content(Baseline and 6-months post treatment (approximately 24 weeks))
- PCr:ATP ratio(Baseline and 6-months post treatment (approximately 24 weeks))
- Myocardial insulin sensitivity(Baseline and 6-months post treatment (approximately 24 weeks))