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The Late Effects of Ethanol Intake on the Glucose Response to Subcutaneous Glucagon in Type 1 Diabetes (ALCO1)

2017年7月20日 更新者:Ajenthen Ranjan、Hvidovre University Hospital

Objective: Because many people with type 1 diabetes drink ethanol and because glucagon is used to treat mild hypoglycaemia, it is essential to determine whether ethanol will impair the effectiveness of glucagon to increase glucose, which may impair the effectiveness of the dual hormone treatment in preventing hypoglycaemia.

The purpose of this study is to determine, whether ethanol influences the glucose response to subcutaneous glucagon during mild hypoglycaemia.

The investigators hypothesize that prior evening ethanol consumption does not reduce the effect of a glucagon bolus to raise plasma glucose compared with no prior ethanol consumption.

The study aims:

  1. To determine the late effects of ethanol on the efficacy of subcutaneous glucagon to restore plasma glucose after an episode of mild hypoglycemia.
  2. To determine the late effects of ethanol on the counter-regulatory hormones and hypoglycaemia awareness during mild hypoglycaemia

A double-blinded placebo-controlled study will be conducted. Participants will serve as their own controls. Eligible participants will after an informed consent complete two study visits, one with and one without ethanol consumption, in a random order. On each study visit, participants are induced a insulin induced hypoglycemia, seven-eight hours after a meal with or without ethanol. Once plasma glucose is below 3.9 mmol/l, a subcutaneous injection of 100 mcg glucagon is administered. Two hours later a second bolus is administered.

研究概览

研究类型

介入性

注册 (实际的)

12

阶段

  • 第四阶段

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习地点

      • Hvidovre、丹麦、2650
        • Hvidovre University Hospital

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 70年 (成人、年长者)

接受健康志愿者

有资格学习的性别

全部

描述

Inclusion Criteria:

  • Age 18 - 70 years
  • T1D ≥ 3 year
  • BMI 20-28 kg/m2
  • CSII ≥ 1 year
  • Caucasian origin
  • Hypoglycaemia awareness (assessed by Gold, Clarke and Pedersen-Bjergaard methods)
  • Use of carbohydrate counting and the insulin pump bolus calculator for all meals
  • Ethanol exposure once within 1 year consisting of at least 4 drinks (1 drink contains 12 gram ethanol) within four hours

Exclusion Criteria:

  • Allergy or intolerance to lactose or Glucagen®(Novo Nordisk, Bagsværd, DK)
  • Allergy for ethanol or any food ingredients that will be used in the study.
  • Impaired renal function (eGFR < 60 ml/min/1.73m2)
  • Liver disease with ALAT > 2.5 times the upper limit of the reference interval
  • Gastropareses (beat-beat variation < 10 beats per min and/or orthostatic systolic blood pressure > 20 mmHg)
  • Insomnia, sleep apnoea or any troubles with sleeping that according to the investigator's assessment makes the individual unsuitable for study participation.
  • Aldehyde dehydrogenase deficiency as determined by a screening questionnaire
  • Unable to refrain from the consumption of ethanol at least 24 hours prior to study start
  • History of drinking problems or alcoholism, regardless of whether active or in remission.
  • Use of benzodiazepines or barbiturates or opiates or other central nervous system depressant drugs that could act synergistically with ethanol to lower the level of consciousness
  • History of drug abuse
  • Current participation in another diabetes-related clinical trial that, in the judgment of the principle investigator, will compromise the results of the study or the safety of the subject.
  • Use of anti-diabetic medicine (other than insulin), corticosteroids or other drugs affecting glucose metabolism during the study period or within 30 days prior to study start
  • Use of medications that are known to cause QT interval prolongation
  • Presence of pheochromocytoma
  • Other concomitant medical or psychological condition that according to the investigator's assessment makes the individual unsuitable for study participation
  • Females who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods.
  • Females who have different basal insulin pattern depending on their menstrual cycle.
  • Inability to understand the individual information and to give informed consent.

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

  • 主要用途:治疗
  • 分配:随机化
  • 介入模型:交叉作业
  • 屏蔽:双倍的

武器和干预

参与者组/臂
干预/治疗
有源比较器:Ethanol
Drinking a cocktail of ethanol (0.8 g ethanol per kg body weight), diet lemonade and water of 1:1:1 (volume distribution).
其他名称:
  • 鸡尾酒
安慰剂比较:Non-ethanol
Drinking a cocktail of diet lemonade and water of 1:2 (volume distribution).
其他名称:
  • 无酒精鸡尾酒

研究衡量的是什么?

主要结果指标

结果测量
措施说明
大体时间
Increase in plasma glucose
大体时间:0-120 min after the first glucagon injection
The primary endpoint is difference in increase in plasma glucose value after the first injection of 100 µg s.c. glucagon on study nights with ethanol vs. study nights without ethanol consumption.
0-120 min after the first glucagon injection

次要结果测量

结果测量
措施说明
大体时间
Peak plasma glucose
大体时间:0-240 min after the first glucagon injection
Maximal plasma glucose after the first and second glucagon injection
0-240 min after the first glucagon injection
Increase in plasma glucose
大体时间:0-120 min after the second glucagon injection
Increase in plasma glucose caused by the second glucagon injection.
0-120 min after the second glucagon injection
Total AUC(0-120)
大体时间:0-240 min after the first glucagon injection
Total area under the glucose curve from 0-120 minutes after each glucagon injection
0-240 min after the first glucagon injection
PI-AUC(0-120)
大体时间:0-240 min after the first glucagon injection
positive incremental area under the glucose curve from 0-120 minutes after each glucagon injection
0-240 min after the first glucagon injection
Tmax
大体时间:0-240 min after the first glucagon injection
Time-to-peak glucose value after each glucagon injection glucagon injection
0-240 min after the first glucagon injection
Time above 4.0mM
大体时间:0-240 min after the first glucagon injection
Duration of glucose above 4.0 mmol/l after first and second glucagon injection
0-240 min after the first glucagon injection
Time above baseline
大体时间:0-240 min after the first glucagon injection
Duration of glucose above baseline after first and second glucagon injection
0-240 min after the first glucagon injection
Rescue rates
大体时间:0-240 min after the first glucagon injection
Numbers of first and second glucagon injections that raises PG > 4.9 mmol/l
0-240 min after the first glucagon injection
Hyperglycemia rates
大体时间:0-240 min after the first glucagon injection
Number of first and second glucagon injections that raises PG > 7.1 mmol/l
0-240 min after the first glucagon injection
Changes in plasma ketone bodies, measured as area under the curve
大体时间:0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in plasma ketone bodies, measured as incremental peak
大体时间:0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in plasma glucagon, measured as area under the curve
大体时间:0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in plasma glucagon, measured as incremental peak
大体时间:0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in insulin, measured as area under the curve
大体时间:0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in insulin, measured as incremental peak
大体时间:0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in growth hormones, measured as area under the curve
大体时间:0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in growth hormones, measured as incremental peak
大体时间:0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in serum corticole, measured as area under the curve
大体时间:0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in serum corticole, measured as incremental peak
大体时间:0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in plasma ethanol, measured as area under the curve
大体时间:0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in plasma ethanol, measured as incremental peak
大体时间:0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in free fatty acids, measured as area under the curve
大体时间:0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in free fatty acids, measured as incremental peak
大体时间:0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in triglycerides, measured as area under the curve
大体时间:0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in triglycerides, measured as incremental peak
大体时间:0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Average in blood pressure
大体时间:0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Average heart rate
大体时间:0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Intensity of hypoglycemia
大体时间:0-240 min after the first glucagon injection
Average changes in Edinburgh Hypoglycaemia Scale over time during insulin and glucagon phase
0-240 min after the first glucagon injection
Cognitive impairment
大体时间:0-240 min after the first glucagon injection
Average scores in cognitive test 30 min before each glucagon injection.
0-240 min after the first glucagon injection
Side effects
大体时间:0-240 min after the first glucagon injection
Average visual analogue scale score from 0-180 min for nausea and headache after glucagon injection
0-240 min after the first glucagon injection
Incidence of vomiting
大体时间:0-240 min after the first glucagon injection
Incidence of vomiting after 0-4 hours after each glucagon injection.
0-240 min after the first glucagon injection
Meal induced glucose excursion
大体时间:0-3 hours after meal
Total and incremental area under the glucose curve from 0-120 and 0-240 min after eating the mixed meal
0-3 hours after meal
Meal induced hormonal changes
大体时间:0-3 hours after meal
Total and incremental area under the glucose curve from 0-120 and 0-240 min after eating the mixed meal
0-3 hours after meal
Nocturnal changes in plasma glucose
大体时间:0-6 hours after start of sleep
Area under the curve during sleep
0-6 hours after start of sleep
Nocturnal changes in corticol
大体时间:0-6 hours after start of sleep
Area under the curve during sleep
0-6 hours after start of sleep
Nocturnal changes in growth hormone
大体时间:0-6 hours after start of sleep
Area under the curve during sleep
0-6 hours after start of sleep
Nocturnal changes in ketones
大体时间:0-6 hours after start of sleep
Area under the curve during sleep
0-6 hours after start of sleep
Nocturnal changes in ethanol
大体时间:0-6 hours after start of sleep
Area under the curve during sleep
0-6 hours after start of sleep
Nocturnal changes in glucagon
大体时间:0-6 hours after start of sleep
Area under the curve during sleep
0-6 hours after start of sleep
Difference between the first second glucagon injection and between both study visits in peak change plasma glucose
大体时间:0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Difference between glucagon injections on both study visits in positive incremental area under the glucose curve from 0-120 minutes
大体时间:0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Difference between glucagon injections on both study visits in total area under the glucose curve from 0-120 minutes
大体时间:0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Difference between glucagon injections on both study visits in time-to-peak glucose value
大体时间:0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Difference between glucagon injections on both study visits in duration of glucose above 4.0 mmol/l after first and second glucagon injection
大体时间:0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Difference between glucagon injections on both study visits in duration of glucose above baseline after first and second glucagon injection
大体时间:0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Difference in glucose sensor data on study night with alcohol vs. study night without alcohol - Mean absolute relative difference (MARD) values of glucose sensors compared with YSI from 7 PM- 8 AM.
大体时间:0-10 hours after meal
Intentions to treat analysis
0-10 hours after meal
Difference in glucose sensor data on study night with alcohol vs. study night without alcohol - Precision absolute relative difference (PARD) 120 min before and 120 after each glucagon injection.
大体时间:0-10 hours after meal
Intentions to treat analysis
0-10 hours after meal
Difference in glucose sensor data on study night with alcohol vs. study night without alcohol - MARD values between glucose sensors 0-120 minutes after each glucagon injection.
大体时间:0-10 hours after meal
Intentions to treat analysis
0-10 hours after meal
Difference in glucose sensor data within 2 days after study night with alcohol vs. study night without alcohol - Time in range (glucose sensor value =4.0-10.0mmol/l)
大体时间:0-2 days after the first glucagon injection
Intentions to treat analysis
0-2 days after the first glucagon injection
Difference in glucose sensor data within 2 days after study night with alcohol vs. study night without alcohol - Time in hypoglycaemia (glucose sensor value < 4.0 mmol/l)
大体时间:0-2 days after the first glucagon injection
Intentions to treat analysis
0-2 days after the first glucagon injection
Difference in glucose sensor data within 2 days after study night with alcohol vs. study night without alcohol - Time in hyperglycaemia (glucose sensor value >10.0mmol/l)
大体时间:0-2 days after the first glucagon injection
Intentions to treat analysis
0-2 days after the first glucagon injection
Difference in glucose sensor data within 2 days after study night with alcohol vs. study night without alcohol - Number of hypoglycaemia episodes (glucose sensor value < 4.0 mmol/l)
大体时间:0-2 days after the first glucagon injection
Intentions to treat analysis
0-2 days after the first glucagon injection
Difference in glucose sensor data between the study period with and without alcohol - Clarke- Error Grid analysis for both sensors compared with YSI during study visit
大体时间:-2 to 4 days after study visits
Intentions to treat analysis
-2 to 4 days after study visits
Difference in glucose sensor data between the study period with and without alcohol - PARD values from day 1-7
大体时间:-2 to 4 days after study visits
Intentions to treat analysis
-2 to 4 days after study visits
Difference in glucose sensor data between the study period with and without alcohol - PARD values <4.0 mmol/L from day 1-7
大体时间:-2 to 4 days after study visits
Intentions to treat analysis
-2 to 4 days after study visits
Difference in glucose sensor data between the study period with and without alcohol - PARD values 4.0-10.0 mmol/L from day 1-7
大体时间:-2 to 4 days after study visits
Intentions to treat analysis
-2 to 4 days after study visits
Difference in glucose sensor data between the study period with and without alcohol PARD values >10.0 mmol/L from day 1-7
大体时间:-2 to 4 days after study visits
Intentions to treat analysis
-2 to 4 days after study visits
Difference in glucose sensor data between the study period with and without alcohol - Number of hypoglycaemia episodes (glucose sensor value < 4.0 mmol/l)
大体时间:-2 to 4 days after study visits
Intentions to treat analysis
-2 to 4 days after study visits

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

调查人员

  • 首席研究员:Ajenthen Ranjan, MD、Hvidovre University Hospital

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始

2016年8月1日

初级完成 (实际的)

2017年1月26日

研究完成 (实际的)

2017年1月26日

研究注册日期

首次提交

2016年8月11日

首先提交符合 QC 标准的

2016年8月23日

首次发布 (估计)

2016年8月26日

研究记录更新

最后更新发布 (实际的)

2017年7月24日

上次提交的符合 QC 标准的更新

2017年7月20日

最后验证

2017年7月1日

更多信息

与本研究相关的术语

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)?

未定

此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.

安慰剂的临床试验

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