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| Name | Class |
|---|---|
| Danish Diabetes Academy | OTHER |
| University of Copenhagen | OTHER |
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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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ethanol | Active Comparator | Drinking a cocktail of ethanol (0.8 g ethanol per kg body weight), diet lemonade and water of 1:1:1 (volume distribution). |
|
| Non-ethanol | Placebo Comparator | Drinking a cocktail of diet lemonade and water of 1:2 (volume distribution). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alcohol | Dietary Supplement |
|
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Peak plasma glucose | Maximal plasma glucose after the first and second glucagon injection | 0-240 min after the first glucagon injection |
| Increase in plasma glucose | Increase in plasma glucose caused by the second glucagon injection. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ajenthen Ranjan, MD | Hvidovre University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hvidovre University Hospital | Hvidovre | 2650 | Denmark |
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| ID | Term |
|---|---|
| D007003 | Hypoglycemia |
| D003922 | Diabetes Mellitus, Type 1 |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D003920 | Diabetes Mellitus |
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| ID | Term |
|---|---|
| D000431 | Ethanol |
| ID | Term |
|---|---|
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
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| Dietary Supplement |
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| 0-120 min after the second glucagon injection |
| 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 |
| 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 |
| Tmax | Time-to-peak glucose value after each glucagon injection glucagon injection | 0-240 min after the first glucagon injection |
| 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 |
| Time above baseline | Duration of glucose above baseline after first and second glucagon injection | 0-240 min after the first glucagon injection |
| Rescue rates | Numbers of first and second glucagon injections that raises PG > 4.9 mmol/l | 0-240 min after the first glucagon injection |
| Hyperglycemia rates | 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 | 0-240 min after the first glucagon injection |
| Changes in plasma ketone bodies, measured as incremental peak | 0-240 min after the first glucagon injection |
| Changes in plasma glucagon, measured as area under the curve | 0-240 min after the first glucagon injection |
| Changes in plasma glucagon, measured as incremental peak | 0-240 min after the first glucagon injection |
| Changes in insulin, measured as area under the curve | 0-240 min after the first glucagon injection |
| Changes in insulin, measured as incremental peak | 0-240 min after the first glucagon injection |
| Changes in growth hormones, measured as area under the curve | 0-240 min after the first glucagon injection |
| Changes in growth hormones, measured as incremental peak | 0-240 min after the first glucagon injection |
| Changes in serum corticole, measured as area under the curve | 0-240 min after the first glucagon injection |
| Changes in serum corticole, measured as incremental peak | 0-240 min after the first glucagon injection |
| Changes in plasma ethanol, measured as area under the curve | 0-240 min after the first glucagon injection |
| Changes in plasma ethanol, measured as incremental peak | 0-240 min after the first glucagon injection |
| Changes in free fatty acids, measured as area under the curve | 0-240 min after the first glucagon injection |
| Changes in free fatty acids, measured as incremental peak | 0-240 min after the first glucagon injection |
| Changes in triglycerides, measured as area under the curve | 0-240 min after the first glucagon injection |
| Changes in triglycerides, measured as incremental peak | 0-240 min after the first glucagon injection |
| Average in blood pressure | 0-240 min after the first glucagon injection |
| Average heart rate | 0-240 min after the first glucagon injection |
| Intensity of hypoglycemia | Average changes in Edinburgh Hypoglycaemia Scale over time during insulin and glucagon phase | 0-240 min after the first glucagon injection |
| Cognitive impairment | Average scores in cognitive test 30 min before each glucagon injection. | 0-240 min after the first glucagon injection |
| 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 |
| Incidence of vomiting | Incidence of vomiting after 0-4 hours after each glucagon injection. | 0-240 min after the first glucagon injection |
| 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 |
| 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 |
| Nocturnal changes in plasma glucose | Area under the curve during sleep | 0-6 hours after start of sleep |
| Nocturnal changes in corticol | Area under the curve during sleep | 0-6 hours after start of sleep |
| Nocturnal changes in growth hormone | Area under the curve during sleep | 0-6 hours after start of sleep |
| Nocturnal changes in ketones | Area under the curve during sleep | 0-6 hours after start of sleep |
| Nocturnal changes in ethanol | Area under the curve during sleep | 0-6 hours after start of sleep |
| Nocturnal changes in glucagon | 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 | 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 | 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 | 0-240 min after the first glucagon injection |
| Difference between glucagon injections on both study visits in time-to-peak glucose value | 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 | 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 | 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. | 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. | 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. | 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) | 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) | 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) | 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) | 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 | 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 | 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 | 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 | 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 | 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) | Intentions to treat analysis | -2 to 4 days after study visits |
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |