Effect of a DPP-IV Inhibitor Treatment on the Secretion of Glucagon in Patients Presenting With Type 1 Diabetes Mellitus With or Without Autonomic Neuropathy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- plasma glucagon concentration
研究概览
简要总结
The purpose of this study is to compare the effect of a single administration of a DPP-IV inhibitor (vildagliptin: Galvus ®) versus no treatment over two populations of diabetic patients: without diabetic autonomic neuropathy (NA, i.e. the control group) and with diabetic autonomic neuropathy (i.e. the neuropathy group). The investigators hypothesize that the therapeutic efficacy of DPP-IV inhibitors is partly mediated by the autonomic nervous system. This hypothesis will be validated if a lower glycemic response to DPP-IV inhibitor treatment is observed for the neuropathy group compared to control.
详细描述
Recently published work has demonstrated in animals that the control of pancreatic hormone secretion is due, at least in part, to the action of GLP-1 on the via the autonomic nervous system. Therefore, rhe investigators hypothesized that altered autonomic nervous system could explain, at least in part, the altered therapeutic efficacy of DPP-IV inhibitors observed in some patients. Our aim is to validate this concept in humans.
The objective of this physiopathological, monocentric, comparative, open, parallel study is to compare the effect of a single administration of a DPP-IV (vildagliptin: Galvus ®) over two populations of type 1 diabetic patients: a control group of 12 patients without diabetic autonomic neuropathy (NA) and a group of 12 patients with NA.
This proof of concept study will enrol type 1 diabetic patients to avoid confounding factors related to endogen insulin secretion and frequent polymedication of type 2 diabetic patients. The response will be evaluated for each patient by the relative difference between pre-and post-glucagon concentrations following a test meal, measured in the absence and presence of treatment with DPP4 inhibitor. Expected results: the DPP-4 inhibitor should lead to a reduction of about 20 to 30% of the glucagon level in patients without NA and a smaller or no decrease in patients with NA.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
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 mellitus
- •multiple daily insulin injections therapy or continuous insulin infusion (insulin pomp) therapy
- •recent (<1 year) written diagnosis of autonomic neuropathy available
- •ewing score > 2 for patients to be included in the "neuropathy" group
- •ewing score <= 0.5 for patients to be included in the '"control" group
- •HbA1C <= 10% at the screening visit and stable (+/- 1%)between the autonomous neuropathy diagnosis and the inclusion visit
排除标准
- •severe chronic renal insufficiency defined by an estimated GFR<30 ml/min calculated by MDRD formula)
- •proliferative retinopathy needing panphotocoagulation
- •hepatic enzymes (ALAT, ASAT) greater than 3 times the upper limit
- •congestive heart failure of NYHA functional class III-IV
- •clinical signs of gastroparesis
- •ongoing gastric emptying therapy
- •history of bariatric surgery
- •galvus therapy contra indications: known allergy or hypersensitivity of princeps or excipients, galactose intolerance, lapp lactase deficiency, glucose - galactose malabsorption
- •ongoing systemic corticoids therapy
- •metformin therapy during the day before each study visit
- •haemoglobin alteration
- •pregnancy or pregnancy willing
- •lactation
- •ongoing clinical study participation
研究组 & 干预措施
neuropathy
patients with autonomic neuropathy
干预措施: Vildagliptin (Drug)
control
patients without autonomic neuropathy (ewing score <= 0.5)
干预措施: Vildagliptin (Drug)
结局指标
主要结局
plasma glucagon concentration
时间窗: 120 min post stantardized meal
次要结局
- GLP-1(T-30, 0, 15, 30, 60, 90, 120, 180 min post standardized meal)
- GIP(T-30,0, 15, 30, 60, 90, 120, 180 min post standardized meal)