Low-dose Glibenclamide in Type 2 Diabetes Mellitus - Part A
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Decrease in fasting plasma glucagon concentration
研究概览
简要总结
Diabetes is a chronic condition that affects 1 in 16 people in the UK, and leads to difficulty controlling blood sugar levels. This is due to an imbalance between two main hormones: insulin, which lowers blood sugar, and glucagon, which causes it to rise. Most current anti-diabetic medications work to improve insulin levels, however research is now shifting to better understand how glucagon levels play a key role in this disease.
Glibenclamide is a type of anti-diabetic medication (sulfonylurea) which is commonly used to increase the amount of insulin released by the pancreatic beta-cells. Studies in mice and human cells from donors with type 2 diabetes have shown that sulfonylureas can also improve glucagon levels when used in very small doses by working on different cells in the pancreas (alpha-cells).
The aim of this study is to find out whether low doses of glibenclamide can improve glucagon levels in patients with type 2 diabetes, and whether in the future this could be used to better control high blood sugar levels, without the risk of causing low blood sugar.
Participants with type 2 diabetes who are diet-controlled or on metformin will be given a liquid containing a low dose of glibenclamide. They will need to attend the OCDEM Clinical Research Unit at the Churchill Hospital, Oxford, for early morning blood tests every 3-4 days over a period of 3 weeks. A continuous glucose monitor will also be fitted during this time.
This study is funded by the NIHR OxBRC.
详细描述
This investigator-initiated clinical trial is a single-centre, open-label, non-randomised, dose-finding study. The am is to investigate whether treatment with low-dose glibenclamide can lead to a decrease in fasting glucagon levels in patients with type 2 diabetes, and whether this has an impact on overall blood glucose control.
It will be conducted in the Clinical Research Unit (CRU) of the Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM) at the Churchill Hospital, Oxford. The aim is to find the dose of glibenclamide that causes a reduction in fasting glucagon levels in patients with T2DM.
Participants will self-administer increasing doses of an oral glibenclamide suspension from 0.3-6mg every 3 or 4 days, over a period of 21 days. They will attend the CRU for fasting pre-dose blood tests for insulin, glucagon, C- peptide and glucose prior to each dose change.
Additionally, participants will have the option of having a continuous glucose monitoring (CGM) sensor attached for the duration of the study, which will be checked and changed at each visit to CRU. This will measure the impact of treatment on overall blood glucose control.
No human trials have used doses of glibenclamide under 5mg previously in the measurement of insulin and glucagon secretion. Our sample size calculations are based on experimental data from isolated human islets from T2DM donors, which were performed in Professor Patrik Rorsman's lab. These suggest that 15 participants (allowing for a 15% dropout) would give the study 80% power to detect a 57% reduction in baseline glucagon levels with an alpha error of 5%.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of T2DM.
- •Age 18 years or over.
- •Diet controlled or on metformin only for diabetic control.
- •Body mass index 40 kg/m2 or less.
- •HbA1c 6.0% to 9.5% (42mmol/mol to 80mmol/mol) inclusive.
排除标准
- •Taking anti-diabetic therapies other than metformin
- •Pregnancy or women of childbearing age without adequate contraception
- •Women who are breastfeeding
- •Major psychiatric disease including diagnosed eating disorders, history of drug or alcohol abuse
- •Known sight-threatening retinopathy
- •Renal impairment (eGFR < 60 ml/min; CKD Stage 3)
- •Abnormal liver function tests (> 1.5 x upper limit of normal range)
- •Known ischaemic heart disease or heart failure
- •Known history of a stroke
- •Known history of porphyria
- •Concomitant use of miconazole or other oral antifungal medication.
- •Known or suspected allergy to trial product or related products
- •Oral steroid treatment 30 days prior to the start or at any time during the trial period.
- •Known malignancy or any other condition or circumstance which, in the opinion of the investigator, would affect the patient's ability to participate in the protocol.
- •Ketoacidosis
- •Felt to be unsuitable to participate in the trial in the opinion of the Chief Investigator.
- •Receipt of any investigational trial drug within 3 month prior to participation in the current trial.
研究组 & 干预措施
Glibenclamide dose titration
Increasing doses of glibenclamide oral suspension from 0.3mg/day to 6mg/day.
干预措施: Glibenclamide (Drug)
结局指标
主要结局
Decrease in fasting plasma glucagon concentration
时间窗: After 3-4 days of treatment at each dose increment
Concentration of plasma glucagon using fasting blood samples prior to each dose change.
次要结局
- Effect on fasting glucose, insulin and C-peptide levels(After 3-4 days of treatment at each dose increment)
- Pre-dose plasma concentration of glibenclamide(After 3-4 days of treatment at each dose increment)
- Overall improvement in glycaemic control throughout the day(After 3-4 days of treatment at each dose increment)