Development of Orally Administered Sodium Propionate to Treat and Prevent Diabetes
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 6
- 主要终点
- Propionate CMax
研究概览
简要总结
The aim of these studies is to firstly determine the pharmacokinetic profile of orally administered enteric coated sodium propionate. Subsequently, the most efficacious dose at improving glucose tolerance following an oral glucose challenge will be determined. The investigators will then determine the mechanism of action of propionate, whether it acts by altering beta cell function directly or by augmenting the incretin effect or both
详细描述
The NHS spends £1M per hour, 10% of its yearly budget, treating diabetes. In the UK cases of diabetes are expected to top 4 million by 2025. There is an urgent need for new therapies. The short chain fatty acid propionate is a natural substance produced by digestion of fermentable carbohydrates. Preclinical and early human data demonstrate it improves pancreatic function and glucose control. The investigators aim to conduct proof of principle studies to determine if oral delivery of propionate improves glucose control in patients at risk of developing diabetes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Study 1: Healthy men and women aged between 18 and 70 years with BMI between 20-25 kg/m2 and with normal fasting blood glucose (below5.5mmol/l and HbA1C less than 5.7% will be eligible to volunteer.
- •Study 2: As for Study
- •Study 3: Cohort 1: Volunteers aged between 30 to 70 with a BMI between 25-35 kg/m2 who do not have impaired fasting glucose and have HbA1c below 5.7%.
- •Cohort 2: Volunteers aged between 30 to 70 years with a BMI between 25-35 kg/m2 who have impaired fasting glucose (between 5.5-7mmol/l) and HbA1C between 5.7% and 6.5%,
排除标准
- •Type 1 or Type 2 Diabetes
- •Gained or lost ≥ 3kg weight in the past three months
- •Taken prescription medicines having an impact on metabolism, appetite regulation, glucose homeostasis and hormonal regulation
- •Taken any dietary supplements in the last 6 months
- •Any chronic illness
- •Cardiovascular disease
- •Excess alcohol intake
- •Current smokers
- •Any gastrointestinal disorder e.g. Crohn's disease, coeliac disease or irritable bowel syndrome
- •A history of drug or alcohol abuse in the last 2 years
- •Pregnancy (all women of child bearing age will undergo a pregnancy test).
- •Pancreatitis
- •Use of medications likely to interfere with glucose metabolism, appetite regulation, hormonal balance.
研究组 & 干预措施
Sodium chloride pill
Study 1: pharmacokinetics Study2: Oral glucose tolerance test Study 3: intravenous glucose tolerance test
干预措施: Oral glucose tolerance test (Procedure)
Sodium chloride pill
Study 1: pharmacokinetics Study2: Oral glucose tolerance test Study 3: intravenous glucose tolerance test
干预措施: Intravenous glucose tolerance test. (Procedure)
Sodium propionate pill
Study 1: pharmacokinetics Study2: Oral glucose tolerance test Study 3: intravenous glucose tolerance test
干预措施: Intravenous glucose tolerance test. (Procedure)
Sodium propionate pill
Study 1: pharmacokinetics Study2: Oral glucose tolerance test Study 3: intravenous glucose tolerance test
干预措施: Oral glucose tolerance test (Procedure)
Sodium chloride pill
Study 1: pharmacokinetics Study2: Oral glucose tolerance test Study 3: intravenous glucose tolerance test
干预措施: Sodium Chloride (Dietary Supplement)
Sodium propionate pill
Study 1: pharmacokinetics Study2: Oral glucose tolerance test Study 3: intravenous glucose tolerance test
干预措施: Sodium propionate (Dietary Supplement)
结局指标
主要结局
Propionate CMax
时间窗: hours (up to 8hrs)
Study 1: Peak plasma concentration of propionate. Dose ranging and pharmacokinetic profile of propionate by Mass spectrometry has been measured at -10, 0, 15, 30, 60, 90, 120, 150, 180, 4h, 6h, 8h (the mean below was estimated first per patient (across all the above time points) and then per arm across the 6 patients)
次要结局
- Total Amount of Insulin Stimulated by Propionate Per Unit Time (Incremental Area Under the Curve)(10 minutes)
- Insulinogenic Index (Change in Insulin Divided by the Change in Glucose Over the First 30 Minutes of the Test)(30mins)
- Insulin Levels in Response to the Absorption of Proprionate (Total Insulin Across All Time Points)(hours (up to 8 hours))