Acute and Chronic Effects of Oral Ketones in Subjects With HFrEF and Diabetes
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Cardiac Efficiency after chronic dosing (Left-ventricular function)
研究概览
简要总结
This study will provide insight into whether cardiac function changes with oral Ketone Esters (KE) administered to patients with Type 2 Diabetes Mellitus (T2DM) and Heart failure with reduced ejection fraction (HFrEF). Plasma ketones are avidly extracted by cardiac muscle and their uptake is not dependent upon insulin or influenced by insulin resistance.
详细描述
After the screening visit, subject will take two separate doses of oral ketones during visit two. Subjects will have their first dose (400mg/kg) upon completion of the baseline Magnetic Resonance Imaging (MRI), and then a second dose (400mg/kg) approximately 1.5 hours after their consumption of the 1st dose. Approximately 1.5 hours after their second dose (3hr since first dose), the subject will undergo a second cardiac MRI. Baseline Blood samples of Beta-hydroxybutyrate (BOHB), acetoacetate (ACAC), Free Fatty Acids (FFA), insulin, c-peptide, glucagon, and an additional 10ml (for storage and later analysis) will be drawn prior to their first dose, then every 30 minutes after their first dose, until completion of the second MRI, then a final blood draw upon completion of the MRI for a total of 8 blood draws during visit 2. An IV catheter will be placed into one antecubital vein by a study nurse for all blood draws during visit 2.
The subject will then be asked to return to complete a third MRI approximately 24 hours after their second MRI. Blood samples for BOHB, acetoacetate (ACAC), insulin, c-peptide and glucagon, and an additional 10 ml will be drawn prior to their third MRI. An IV catheter will be placed into one antecubital vein by a study nurse for all blood draws during visit 3.
After completion of the third MRI, subjects will be dosed KE 400mg/kg once daily until the visit 4 MRI can be completed.
Blood samples for BOHB, acetoacetate (ACAC), insulin, c-peptide, glucagon, proBNP, and an additional 10 ml will be drawn prior to their fourth MRI. An IV catheter will be placed into one antecubital vein by a study nurse for all blood draws during visit 4. The 4th MRI, based on subject and scanner availability at approximately Day 7
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Subjects must be on a stable dose of guideline-directed medications for Heart Failure (HF).
- •Patients will have an established diagnosis of HF before the screening visit, documented by an acceptable imaging modality in the last 6 months.
- •Age = 18-80 y
- •Body Mass Index (BMI) =23-38 kg/m2
- •Glycated hemoglobin (HbA1c) = 6.0-10.0%
- •Blood Pressure (BP) < 145/85 mmHg
- •Estimated Glomerular Filtration Rate (eGFR) > 30 ml/min•1.73 m2
- •For women of child-bearing age (WOCBA) willingness to use contraception, if applicable.
排除标准
- •Patients treated with Sodium-Glucose Transport Protein (SGLT2i's) or medications that may impair heart function or acutely worsen glycemic control will be excluded.
- •Pregnancy, lactation, or plans to become pregnant. A negative pregnancy test will be performed before each Magnetic resonance imaging (MRI) study to assess current status.
- •Allergy/sensitivity to study drugs or their ingredients.
- •Current drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
- •Inability or unwillingness of individual or legal guardian/representative to give written informed consent.
- •Subjects with a history of cancer (except basal or squamous cell cancer that has been resolved/remission for 5 years)
- •Cardiovascular event within the last 3 months
- •Major organ or metabolic diseases, or physical limitations that will not allow the subject to complete the study.
研究组 & 干预措施
Ketone Ester administration
- Monitored administration of oral Ketone monoester at 400mg/kg dosed twice on visit 2 (cardiac MRI day)
- Self administered oral β-hydroxybutyrate (BOHB) at 400mg/kg/day for a period of 6 days
干预措施: Ketone Monoester (KE) (Drug)
结局指标
主要结局
Cardiac Efficiency after chronic dosing (Left-ventricular function)
时间窗: 1.5 hours to 7 days
Change in cardiac efficiency after chronic (7 day) dosing of KE, measured by change in Left-Ventricular function measured using Cardiac MRI and expressed as a percentage.
Cardiac Efficiency after acute dose (Left-ventricular function)
时间窗: 1.5 hours to 24 hours
Change in cardiac efficiency after acute dosing of KE, measured by change in Left-ventricular function measured using Cardiac MRI and expressed as a percentage.
次要结局
- Insulin/C-peptide(Baseline to 7 days)
- Beta-hydroxybutyrate(Baseline to 7 days)
- Six minute walk test(Baseline to 7 days)
- Free Fatty Acids (FFAs)(Baseline to 7 days)
- Patient Reported Outcomes Measure Information System (PROMIS) - Physical Function(Baseline to 7 days)
- Acetoacetate(Baseline to 7 days)
- Glucose(Baseline to 7 days)
- Glucagon(Baseline to 7 days)