Effect of the GLP-1 Receptor Agonist Exenatide on Impaired Hypoglycaemic Awareness in Type 1 Diabetes
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Symptom score in response to insulin-induced hypoglycaemia
研究概览
简要总结
Approximately 25% of patients with type 1 diabetes have lost the capacity to timely detect hypoglycaemia, a condition referred to as impaired hypoglycaemic awareness (IHA) that causes a six-fold higher risk of severe, potentially hazardous, hypoglycaemia. IHA is usually the end-result of a process of habituation to recurrent hypoglycemia that is potentially reversible. Treatment with glucagon-like peptide (GLP)-1 Receptor Agonists (1RAs) in addition to insulin therapy may decrease the incidence of hypoglycaemia in patients with type 1 diabetes. This study will test the hypothesis that treatment with the GLP-1RA, exenatide, added to basal-bolus insulin therapy will improve awareness of hypoglycaemia in patients with type 1 diabetes and IHA. In a randomized doubleblind placebo-controlled cross-over trial, patients will be treated for 6 weeks with exenatide (or placebo), after which hypoglycemic symptoms and counterregulatory hormone responses will be examined during a hyperinsulinemic hypoglycemic glucose clamp study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, 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
- 否
入选标准
- •Type 1 diabetes, disease duration >1 year
- •Age >18 years, <70 years
- •Insulin treatment according to basal-bolus insulin regimen (injections or insulin pump)
- •Impaired hypoglycaemic awareness as assessed by a score of 3 or more on the modified Dutch translation of the Clarke questionnaire
- •Glycated haemoglobin (HbA1c) ≥42 mmol/mol (6%) and ≤75 mmol/mol (9.0%)
- •Ability to provide informed consent
排除标准
- •Treatment with incretin-based therapy
- •Known intolerance to GLP-1RAs (including allergy)
- •Treatment with glucose-modifying or immune-modifying agents, e.g. prednisolon
- •Recent history of myocardial infarction or stroke (past year) or laser coagulation for proliferative retinopathy (past 6 months)
- •Proliferative retinopathy
- •Symptomatic diabetic neuropathy
- •Diabetic nephropathy as reflected by albumin-creatinin ratio >30 mmol/mg or estimated Glomerular Filtration Rate (eGFR) <60 ml/min/1.73 m2
- •Known heart failure
- •History of pancreatitis (acute or chronic) or pancreatic cancer
- •Body-mass index >40 kg/m2
- •Use of premixed insulin or of long-acting insulin alone
- •Total daily insulin dose requirements <20 units unless on pump treatment
- •Pregnancy or unwillingness to undertake measures for birth control
研究组 & 干预措施
EXENATIDE
Exenatide
- week 1-2: 5 µg twice daily
- week 3-6: 10 µg twice daily (if tolerated)
干预措施: Exenatide (Drug)
PLACEBO
Placebo matched to exenatide
- week 1-2: 5 µg twice daily
- week 3-6: 10 µg twice daily (if tolerated)
干预措施: Placebo (Drug)
结局指标
主要结局
Symptom score in response to insulin-induced hypoglycaemia
时间窗: 30 minutes
Measured during hyperinsulinemic hypoglycaemic glucose clamps
次要结局
- Adrenaline response to insulin-induced hypoglycaemia(30 minutes)
- Glucagon response to insulin-induced hypoglycaemia(30 minutes)
- Time until glycaemic recovery from hypoglycaemia(1 hour)
- Maximal glucose excursion post-hypoglycaemia(1 hour)
- Time until glucose peak post-hypoglycaemia(1 hour)
- Area under the glucose concentration curve post-hypoglycaemia(1 hour)
- Hunger score post-hypoglycaemia(1 hour)
- Carbohydrate requirement after recovery from hypoglycaemia(1 hour)
- Number of severe hypoglycaemic events during follow-up(16 weeks)
- Number of nocturnal hypoglycaemic events during follow-up(16 weeks)
- Number of any hypoglycaemic events during follow-up(16 weeks)
- Number of hypoglycaemic events measured by glucose sensor monitoring(1 week)
- Time spent under hypoglycaemic conditions measured by glucose sensor monitoring(1 week)
- Glucose variability as measured by glucose sensor monitoring(1 week)