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

Diabetes Mellitus, Type 1 Clinical Trial

— ALCO1  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02881060
• Other study ID #: H-16027080
• Status: Completed
• Phase: Phase 4
• First received: August 11, 2016
• Last updated: July 20, 2017
• Start date: August 2016
• Est. completion date: January 26, 2017

Study information

• Verified date: July 2017
• Source: Hvidovre University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: January 26, 2017
• Est. primary completion date: January 26, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Alcohol Drinking
• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Hypoglycemia

Intervention

Dietary Supplement:
• Alcohol

• Placebo

Locations

Country	Name	City	State
Denmark	Hvidovre University Hospital	Hvidovre

Sponsors (3)

Lead Sponsor	Collaborator
Hvidovre University Hospital	Danish Diabetes Academy, University of Copenhagen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Increase in plasma glucose	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
Secondary	Peak plasma glucose	Maximal plasma glucose after the first and second glucagon injection	0-240 min after the first glucagon injection
Secondary	Increase in plasma glucose	Increase in plasma glucose caused by the second glucagon injection.	0-120 min after the second glucagon injection
Secondary	Total AUC(0-120)	Total area under the glucose curve from 0-120 minutes after each glucagon injection	0-240 min after the first glucagon injection
Secondary	PI-AUC(0-120)	positive incremental area under the glucose curve from 0-120 minutes after each glucagon injection	0-240 min after the first glucagon injection
Secondary	Tmax	Time-to-peak glucose value after each glucagon injection glucagon injection	0-240 min after the first glucagon injection
Secondary	Time above 4.0mM	Duration of glucose above 4.0 mmol/l after first and second glucagon injection	0-240 min after the first glucagon injection
Secondary	Time above baseline	Duration of glucose above baseline after first and second glucagon injection	0-240 min after the first glucagon injection
Secondary	Rescue rates	Numbers of first and second glucagon injections that raises PG > 4.9 mmol/l	0-240 min after the first glucagon injection
Secondary	Hyperglycemia rates	Number of first and second glucagon injections that raises PG > 7.1 mmol/l	0-240 min after the first glucagon injection
Secondary	Changes in plasma ketone bodies, measured as area under the curve		0-240 min after the first glucagon injection
Secondary	Changes in plasma ketone bodies, measured as incremental peak		0-240 min after the first glucagon injection
Secondary	Changes in plasma glucagon, measured as area under the curve		0-240 min after the first glucagon injection
Secondary	Changes in plasma glucagon, measured as incremental peak		0-240 min after the first glucagon injection
Secondary	Changes in insulin, measured as area under the curve		0-240 min after the first glucagon injection
Secondary	Changes in insulin, measured as incremental peak		0-240 min after the first glucagon injection
Secondary	Changes in growth hormones, measured as area under the curve		0-240 min after the first glucagon injection
Secondary	Changes in growth hormones, measured as incremental peak		0-240 min after the first glucagon injection
Secondary	Changes in serum corticole, measured as area under the curve		0-240 min after the first glucagon injection
Secondary	Changes in serum corticole, measured as incremental peak		0-240 min after the first glucagon injection
Secondary	Changes in plasma ethanol, measured as area under the curve		0-240 min after the first glucagon injection
Secondary	Changes in plasma ethanol, measured as incremental peak		0-240 min after the first glucagon injection
Secondary	Changes in free fatty acids, measured as area under the curve		0-240 min after the first glucagon injection
Secondary	Changes in free fatty acids, measured as incremental peak		0-240 min after the first glucagon injection
Secondary	Changes in triglycerides, measured as area under the curve		0-240 min after the first glucagon injection
Secondary	Changes in triglycerides, measured as incremental peak		0-240 min after the first glucagon injection
Secondary	Average in blood pressure		0-240 min after the first glucagon injection
Secondary	Average heart rate		0-240 min after the first glucagon injection
Secondary	Intensity of hypoglycemia	Average changes in Edinburgh Hypoglycaemia Scale over time during insulin and glucagon phase	0-240 min after the first glucagon injection
Secondary	Cognitive impairment	Average scores in cognitive test 30 min before each glucagon injection.	0-240 min after the first glucagon injection
Secondary	Side effects	Average visual analogue scale score from 0-180 min for nausea and headache after glucagon injection	0-240 min after the first glucagon injection
Secondary	Incidence of vomiting	Incidence of vomiting after 0-4 hours after each glucagon injection.	0-240 min after the first glucagon injection
Secondary	Meal induced glucose excursion	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
Secondary	Meal induced hormonal changes	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
Secondary	Nocturnal changes in plasma glucose	Area under the curve during sleep	0-6 hours after start of sleep
Secondary	Nocturnal changes in corticol	Area under the curve during sleep	0-6 hours after start of sleep
Secondary	Nocturnal changes in growth hormone	Area under the curve during sleep	0-6 hours after start of sleep
Secondary	Nocturnal changes in ketones	Area under the curve during sleep	0-6 hours after start of sleep
Secondary	Nocturnal changes in ethanol	Area under the curve during sleep	0-6 hours after start of sleep
Secondary	Nocturnal changes in glucagon	Area under the curve during sleep	0-6 hours after start of sleep
Secondary	Difference between the first second glucagon injection and between both study visits in peak change plasma glucose		0-240 min after the first glucagon injection
Secondary	Difference between glucagon injections on both study visits in positive incremental area under the glucose curve from 0-120 minutes		0-240 min after the first glucagon injection
Secondary	Difference between glucagon injections on both study visits in total area under the glucose curve from 0-120 minutes		0-240 min after the first glucagon injection
Secondary	Difference between glucagon injections on both study visits in time-to-peak glucose value		0-240 min after the first glucagon injection
Secondary	Difference between glucagon injections on both study visits in duration of glucose above 4.0 mmol/l after first and second glucagon injection		0-240 min after the first glucagon injection
Secondary	Difference between glucagon injections on both study visits in duration of glucose above baseline after first and second glucagon injection		0-240 min after the first glucagon injection
Secondary	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.	Intentions to treat analysis	0-10 hours after meal
Secondary	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.	Intentions to treat analysis	0-10 hours after meal
Secondary	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.	Intentions to treat analysis	0-10 hours after meal
Secondary	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)	Intentions to treat analysis	0-2 days after the first glucagon injection
Secondary	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)	Intentions to treat analysis	0-2 days after the first glucagon injection
Secondary	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)	Intentions to treat analysis	0-2 days after the first glucagon injection
Secondary	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)	Intentions to treat analysis	0-2 days after the first glucagon injection
Secondary	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	Intentions to treat analysis	-2 to 4 days after study visits
Secondary	Difference in glucose sensor data between the study period with and without alcohol - PARD values from day 1-7	Intentions to treat analysis	-2 to 4 days after study visits
Secondary	Difference in glucose sensor data between the study period with and without alcohol - PARD values <4.0 mmol/L from day 1-7	Intentions to treat analysis	-2 to 4 days after study visits
Secondary	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	Intentions to treat analysis	-2 to 4 days after study visits
Secondary	Difference in glucose sensor data between the study period with and without alcohol PARD values >10.0 mmol/L from day 1-7	Intentions to treat analysis	-2 to 4 days after study visits
Secondary	Difference in glucose sensor data between the study period with and without alcohol - Number of hypoglycaemia episodes (glucose sensor value < 4.0 mmol/l)	Intentions to treat analysis	-2 to 4 days after study visits