Influence of Apelin on Insulin Sensitivity in Type 2 Diabetic Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Delta between Glucose Infusion Rate
研究概览
简要总结
Preclinical studies have demonstrated in mouse models that (PYR1)-apelin-13 exerts a glucose-regulating action in vivo. The (PYR1)-apelin-13 effect on insulin sensitivity in healthy overweighed volunteers has been previously assessed in a phase I clinical trial (APELINS study; NCT02033473). The APELINS-2 clinical trial aims to expand the initial proof of concept to the population targeted by future innovative insulin-sensitizing therapies: patients living with type 2 diabetes.
详细描述
Insulin sensitivity is measured using the hyperinsulinemic euglycemic glucose clamp method. The hypothesis of the investigators is that a continuous (pyr1)-apelin-13 infusion improves insulin sensitivity of type 2 diabetic patients compared to placebo infusion.
This study could bring new elements for understanding the pathophysiology of insulin resistance and type 2 diabetes mellitus in humans and could lead to the development of innovative therapies in type 2 diabetes mellitus.
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, Investigator)
入排标准
- 年龄范围
- 40 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnosis of type2 diabetes
- •Body Mass Index between 27 and 33 kg / cm ²
- •HbA1c < 8.5%
- •Non-pathological Electrocardiogram
- •Heart rate between 50 and 80 beats per minute at rest.
- •Complete Blood Count (CBC) with no significant anomaly in terms of the investigator..
- •Serum electrolytes without clinically significant abnormalities in terms of the investigator.
- •Liver function tests without clinically significant abnormalities in terms of the investigator
- •Renal function tests without clinically significant abnormalities in terms of the investigator
- •Good peripheral vein (forearm and back of the hand).
- •Agreement to participate in the establishment of a serum bank.
- •Ability to sign informed consent.
- •Affiliation to a social security scheme
排除标准
- •Secondary prevention of cardio-vascular disease
- •Insulin therapy or Glucagon Like Peptid 1 (GLP-1) analogs therapy in the 6 months before inclusion.
- •Risk factor, treatment or electrocardiogram as recommended by International Conference on Harmonization (ICH) E14 "Clinical Evaluation of QT / QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs"
- •Repeated a QTc interval> 450 ms measurement
- •Risk factor for torsade de pointes: myocardial infarction, hypokalemia, family history of long QT syndrome
- •Personal history of cancer.
- •Positive HIV serology.
- •Hepatitis B serology positive.
- •Positive hepatitis C serology.
- •Cognitive impairment or mental illness (at the discretion of the investigator).
- •Chronic excessive alcohol consumption (consumption > 30g/day or 210g/week).
- •Person under judicial protection, guardianship.
- •Subject with a resting systolic blood pressure greater than 140 mm Hg and diastolic blood pressure greater than 90 mmHg
- •Smoking more than 10 cigaret per day and can not be interrupted for 24 hours.
研究组 & 干预措施
Apelin then Placebo
First clamp during which an apelin infusion will be administered followed by a wash-out period and then, a second clamp in which a placebo infusion will be administered
干预措施: apelin (Drug)
Apelin then Placebo
First clamp during which an apelin infusion will be administered followed by a wash-out period and then, a second clamp in which a placebo infusion will be administered
干预措施: placebo (Drug)
Placebo then Apelin
First clamp during which a placebo infusion will be administered followed by a wash-out period and then, a second clamp in which an apelin infusion will be administered
干预措施: apelin (Drug)
Placebo then Apelin
First clamp during which a placebo infusion will be administered followed by a wash-out period and then, a second clamp in which an apelin infusion will be administered
干预措施: placebo (Drug)
结局指标
主要结局
Delta between Glucose Infusion Rate
时间窗: 240 minutes
Difference between glucose infusion rate measured during investigational product infusion (mean of values measured at 210, 215, 220, 225, 230, 235 and 240 minutes) and basal glucose infusion rate (mean of values measured at 90, 95, 100, 105, 110, 115 and 120 minutes).
次要结局
- Measure of M-value (a glucose physiological parameter)(240 minutes)
- systolic blood pressure and diastolic blood pressure(240 minutes)
- heart rate(240 minutes)
- Measure of QTc interval with electrocardiogram examination(240 minutes)
- Clinic sign of apelin intolerance(240 minutes)
- Dosage of plasma proteins(240 minutes)
- Clinic sign of apelin allergy(240 minutes)
- Clinic sign of apelin toxicity(240 minutes)