Effect of Ethanol Intoxication on the Anti-hypoglycemic Action of Glucagon
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Enrollment
- 26
- Locations
- 1
- Primary Endpoint
- AOCGIR (Area Over the Curve for Glucose Infusion Rate)
Study Overview
Brief Summary
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
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 21 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
Glucagon with Ethanol
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.
Intervention: Ethanol (Drug)
Glucagon with Ethanol
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.
Intervention: Glucagon (Drug)
Glucagon without Ethanol
Volunteers will not receive an infusion of IV ethanol at this visit. 50 micrograms of glucagon will be administered via subcutaneous injection.
Intervention: Glucagon (Drug)
Outcomes
Primary Outcomes
AOCGIR (Area Over the Curve for Glucose Infusion Rate)
Time Frame: 1 Day Visit (approximately 8 to 11 hours)
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%
Secondary Outcomes
- Maximum Change in GIR (Glucose Infusion Rate) From Baseline(1 Day Visit (approximately 8 to 11 hours))
Investigators
Steven J. Russell, MD, PhD
Assistant Professor of Medicine
Massachusetts General Hospital