Effects of 6 Weeks Treatment With a Dipeptidyl Peptidase 4 Inhibitor on Counterregulatory and Incretin Hormones During Acute Hypoglycaemia in Patients With Type 1 Diabetes: a Randomized Double Blind Placebo-controlled Cross-over Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Glucagon Response to Acute Hypoglycaemia
研究概览
简要总结
Hypoglycaemia is a well-known complication of insulin treated diabetes. The counterregulatory response to hypoglycaemia, with glucagon as the most important mediator, is initially diminished within a few years of onset of Type 1 diabetes and subsequently lost and thus increasing the risk of hypoglycaemia. Dipeptidyl Peptidase (DPP)-4 inhibitors augment the glucagon response to insulin-induced hypoglycaemia in type 2 diabetes. The investigators hypothesize that treatment with a DPP-4 inhibitor in patients with type 1 diabetes will recover the alpha cell response to hypoglycaemia.
详细描述
The 16 type 1 patients will be randomised to one of two treatment sequences: DPP-4 inhibitor followed by placebo or placebo followed by a DPP-4 inhibitor. Each treatment period lasts 6 weeks, so all patients will receive treatment for 12 weeks in total. Induction of hypoglycaemia will take place at 0 weeks, 6 weeks and 12 weeks to determine the glucagon response.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Type 1 Diabetes Mellitus 5-20 years duration
- •C-peptide negative
- •Willing and able to give written informed consent
排除标准
- •Impaired awareness of hypoglycaemia
- •BMI > 27 kg/m2
- •Evidence of severe diabetes complications (autonomic neuropathy, macroalbuminuria, proliferative retinopathy)
- •Acute illness within 3 months before the study
- •Significant renal impairment (creatinine clearance < 50ml/min)
- •Use of beta-adrenoreceptor blockers
- •Cardiac history (previous arrhythmia)
- •History of epilepsy
研究组 & 干预措施
Sequence A (sitagliptin→placebo)
Cross-over, both arms reveived the same intervention in different order.
干预措施: Sitagliptin (Drug)
Sequence A (sitagliptin→placebo)
Cross-over, both arms reveived the same intervention in different order.
干预措施: Placebo (Drug)
Sequence B (placebo→sitagliptin)
Cross-over, both arms reveived the same intervention in different order.
干预措施: Sitagliptin (Drug)
Sequence B (placebo→sitagliptin)
Cross-over, both arms reveived the same intervention in different order.
干预措施: Placebo (Drug)
结局指标
主要结局
Glucagon Response to Acute Hypoglycaemia
时间窗: 0, 10, 20 and 40 minutes
Area under the curve (AUC) from onset of the autonomic response to hypoglycaemia to 40 minutes after onset of the autonomic response. AUC values were calculated by the trapezoid method.
次要结局
- Epinephrine Response to Acute Hypoglycaemia(0, 10, 20, 40 minutes)
- Intact and Total Glucagon Like Peptide-1 (GLP-1), Intact and Total Gastric Inhibitory Peptide (GIP) Response to Acute Hypoglycaemia(0, 10, 20, 40 minutes)
- Cortisol Response to Acute Hypoglycaemia(0, 10, 20, 40 minutes)
- Norepinephrine Response to Acute Hypoglycaemia(0, 10, 20, 40 minutes)
- Growth Hormone Response to Acute Hypoglycaemia(0, 10, 20, 40 minutes)
- Symptomatic Hormone Responses to Acute Hypoglycaemia.(Change from baseline symptomatic response at hypoglycaemia and 30 minutes after hypoglycaemia)
研究者
F Holleman
PhD, MD
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)