Effect of the SGLT-2 Inhibitor Dapagliflozin on Impaired Awareness of Hypoglycemia in Type 1 Diabetes
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 15
- 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 awareness of hypoglycaemia (IAH) that causes a six-fold higher risk of severe, potentially hazardous, hypoglycaemia. IAH is usually the end-result of a process of habituation to recurrent hypoglycaemia that is potentially reversible. Treatment with sodium glucose cotransporter (SGLT)-2 inhibitors (SGLT-2i) 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 SGLT-2 inhibitor, dapagliflozin, added to basal-bolus insulin therapy will improve awareness of hypoglycaemia in patients with type 1 diabetes and IAH. In a randomized doubleblind placebo-controlled cross-over trial, patients will be treated for 8 weeks with dapagliflozin (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 75 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, <75 years
- •BMI 19-40 kg/m^2
- •Insulin treatment according to basal-bolus insulin regimen (injections or insulin pump)
- •Impaired awareness of hypoglycemia 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 SGLT-2 inhibitors
- •Known intolerance to SGLT-2 inhibitors
- •Treatment with loop diuretics or other anti-hypertensive agents
- •Treatment with glucose-modifying (other than insulin) or immune-modifying agents (e.g. prednisolon)
- •Treatment with pioglitazone
- •Use of statins
- •A history of cardiovascular disease (e.g. myocardial infarction, stroke, heart failure) or hypotension
- •A history of galactose-intolerance, lactase deficiency, glucose-galactose malabsorption
- •History of diabetic ketoacidosis requiring medical intervention within 1 month before screening
- •Admission to the hospital for hyperglycemia or hypoglycemia within 1 month before screening
- •Frequent episodes of severe hypoglycemia within 1 month before screening
- •Laser coagulation for proliferative retinopathy (past 6 months)
- •Proliferative retinopathy
- •Diabetic nephropathy as reflected by an albumin-creatinin ratio ˃ 30 mmol/mg or an estimated glomerular filtration rate (by MDRD) ˂60ml/min/1.73m2
- •History of pancreatitis (acute or chronic) or pancreatic cancer
- •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
Dapagliflozin
Dapagliflozin 10 mg capsule once daily for 8 weeks
干预措施: Dapagliflozin (Drug)
Placebo oral capsule
Placebo matched to dapagliflozin 10 mg capsule once daily for 8 weeks
干预措施: Placebo oral capsule (Drug)
结局指标
主要结局
Symptom score in response to insulin-induced hypoglycaemia
时间窗: 45 minutes
Symptom scores (autonomic, neuroglycopenic and general) measured during hyperinsulinemic hypoglycaemic glucose clamps. This questionnaire consists of 18 symptoms, which can be scored between 0 (none) to 6 (severe). Total scores range between 0 and 108, the higher the score, the more symptoms patients have during and after hypoglycemia.
次要结局
- Number of nocturnal hypoglycaemic events during follow-up(16 weeks)
- Counterregulatory hormone responses to insulin-induced hypoglycaemia(45 minutes)
- Time until glycaemic recovery from hypoglycaemia(45 minutes)
- Maximal glucose excursion post-hypoglycaemia(45 minutes)
- Time until glucose peak post-hypoglycaemia(45 minutes)
- Area under the glucose concentration curve post-hypoglycaemia(45 minutes)
- Number of severe hypoglycaemic events during follow-up(16 weeks)
- Number of any hypoglycaemic events during follow-up(16 weeks)
- Time spent under hypoglycaemic conditions measured by glucose sensor monitoring(2 weeks)
- Glucose variability as measured by glucose sensor monitoring(2 weeks)