Effect of Ethanol Intoxication on the Anti-Hypoglycemic Action of Glucagon

Study Overview
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Brief Summary
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This study will test the hypothesis that a BAC (blood alcohol content) of 0.1% will not significantly alter the anti-hypoglycemic effect of mico-dose glucagon in individuals with type 1 diabetes.

Detailed Description
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This study will test the hypothesis that a BAC (blood alcohol content) of 0.1% will not significantly alter the anti-hypoglycemic effect of mico-dose glucagon in individuals with type 1 diabetes. The study will aim to quantify the effect of a blood alcohol content on the anti-hypoglycemic efficacy of glucagon using a hyperinsulinemic -normoglycemic clamp technique in volunteers with type 1 diabetes in a randomized crossover trial.

Official Title
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Effect of Ethanol Intoxication on the Anti-hypoglycemic Action of Glucagon

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: Ethanol
* Drug: Glucagon


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 21 to 80 years old with type 1 diabetes for at least one year. Diabetes managed using an insulin infusion pump using rapid-acting insulin such as insulin aspart (NovoLog), insulin lispro (Humalog), or insulin glulisine (Apidra) for at least one week prior to enrollment. Alcohol exposure on at least one occasion in the last year consisting of at least 4 drinks in one sitting. Exclusion Criteria: Unable to provide informed consent. Unable to comply with study procedures. Unable to refrain from the consumption of alcohol at least 24 hours prior to study start. Current participation in another diabetes-related clinical trial that, in the judgment of the principle investigator, will compromise the results of the clamp study or the safety of the subject. Pregnancy (positive urine HCG), breast feeding, plan to become pregnant in the immediate future, or sexually active without use of contraception. Aldehyde dehydrogenase deficiency as determined by a screening questionnaire End stage renal disease on dialysis (hemodialysis or peritoneal dialysis). History of pheochromocytoma (because glucagon has been reported to precipitate hypertensive crisis in the setting of pheochromocytoma). Fractionated metanephrines will be tested in patients with a history increasing the risk for a catecholamine secreting tumor: Paroxysms of tachycardia, pallor, or headache. Personal or family history of MEN 2A, MEN 2B, neurofibromatosis, or von Hippel-Lindau disease, Episodic or treatment of refractory (requiring 4 or more medications to achieve normotension) hypertension. History of adverse reaction to glucagon (including allergy) besides nausea, vomiting, or headache. Inadequate venous access as determined by study nurse or physician at time of screening. Liver failure or cirrhosis Hemoglobin < 12 gm/dl. History of problem drinking 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 Any other factors that, in the judgment of the principal investigator, would interfere with the safe completion of the study procedures.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glucagon with Ethanol<br>Volunteers will receive an infusion of IV ethanol that will increase their BAC (blood alcohol content) to 0.1. Once their BAC has stabilized at 0.1%, 50 micrograms of glucagon will be administered via subcutaneous injection. | Drug: Ethanol<br>* IV infusion of ethanol to stabilize BAC (blood alcohol content) at 0.1%<br>* Other names: Alcohol;Drug: Glucagon<br>* injection of 50 micrograms of glucagon<br>|
| Active Comparator: Glucagon without Ethanol<br>Volunteers will not receive an infusion of IV ethanol at this visit. 50 micrograms of glucagon will be administered via subcutaneous injection. | Drug: Glucagon<br>* injection of 50 micrograms of glucagon<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AOCGIR (Area Over the Curve for Glucose Infusion Rate) | Area over the curve for the glucose infusion rate in the hour following a subcutaneous glucagon dose with a blood alcohol content of 0 vs 0.1% | 1 Day Visit (approximately 8 to 11 hours) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Change in GIR (Glucose Infusion Rate) From Baseline | This outcome is measuring the maximum change in the glucose infusion rate from the GIR at the time of the injection through the 90 minutes after the glucagon injection in the presence and absence of ethanol. The glucose infusion rate is adjusted up to every two minutes throughout the clamp, and for 90 minutes total after the glucagon injection. | 1 Day Visit (approximately 8 to 11 hours) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 1 Diabetes, Bionic Pancreas, Artificial Pancreas, Insulin, Glucagon, Alcohol, Alcohol Clamp