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

Mass General Brigham

Status and phase: Completed; Phase 4

Conditions: Type 1 Diabetes Mellitus

Treatments: Drug: Glucagon; Drug: Ethanol

Study type: Interventional

Funder types: Other

Identifiers

NCT02516150

2015P001323

Details and patient eligibility

About

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.

Full 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.

Enrollment: 26 patients

Sex: All

Ages: 21 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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26 participants in 2 patient groups

Glucagon with Ethanol

Experimental group

Description:

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.

Treatment:

Drug: Ethanol

Drug: Glucagon

Glucagon without Ethanol

Active Comparator group

Description:

Volunteers will not receive an infusion of IV ethanol at this visit. 50 micrograms of glucagon will be administered via subcutaneous injection.

Treatment:

Drug: Glucagon