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

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

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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Drug: Ethanol; Drug: Glucagon

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 Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Diabetes Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

• 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Ethanol; IV infusion of ethanol to stabilize BAC (blood alcohol content) at 0.1%; Other Names: Alcohol; Ethyl Alcohol; Drug: Glucagon; injection of 50 micrograms of glucagon
Active Comparator: 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.	Drug: Glucagon; injection of 50 micrograms of glucagon

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2016
• Primary Completion (Actual): May 1, 2017
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: July 28, 2015
• First Submitted That Met QC Criteria: August 3, 2015
• First Posted (Estimate): August 5, 2015

Study Record Updates

• Last Update Posted (Actual): August 31, 2017
• Last Update Submitted That Met QC Criteria: July 31, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Insulin; Alcohol; Type 1 Diabetes; Artificial Pancreas; Glucagon; Bionic Pancreas; Alcohol Clamp
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Physiological Effects of Drugs; Anti-Infective Agents, Local; Anti-Infective Agents; Central Nervous System Depressants; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Ethanol; Glucagon
• Other Study ID Numbers: 2015P001323

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No