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

Primary Purpose

Type 1 Diabetes Mellitus

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Ethanol

Glucagon

About this trial

This is an interventional treatment trial for Type 1 Diabetes Mellitus focused on measuring Type 1 Diabetes, Bionic Pancreas, Artificial Pancreas, Insulin, Glucagon, Alcohol, Alcohol Clamp

Eligibility Criteria

21 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Massachusetts General Hospital Diabetes Research Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Glucagon with Ethanol

Glucagon without Ethanol

Arm 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.

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

Outcomes

Primary Outcome Measures

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%

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT02516150

First Posted

July 28, 2015

Last Updated

July 31, 2017

Sponsor

Massachusetts General Hospital

1. Study Identification

Unique Protocol Identification Number

NCT02516150

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2017

Overall Recruitment Status

Completed

Study Start Date

March 2016 (Actual)

Primary Completion Date

May 2017 (Actual)

Study Completion Date

June 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Massachusetts General Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 1 Diabetes Mellitus

Keywords

Type 1 Diabetes, Bionic Pancreas, Artificial Pancreas, Insulin, Glucagon, Alcohol, Alcohol Clamp

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

26 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Glucagon with Ethanol

Arm Type

Experimental

Arm Description

Arm Title

Glucagon without Ethanol

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Ethanol

Other Intervention Name(s)

Ethyl Alcohol, Alcohol

Intervention Description

IV infusion of ethanol to stabilize BAC (blood alcohol content) at 0.1%

Intervention Type

Drug

Intervention Name(s)

Glucagon

Intervention Description

injection of 50 micrograms of glucagon

Primary Outcome Measure Information:

Title

AOCGIR (Area Over the Curve for Glucose Infusion Rate)

Description

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%

Time Frame

1 Day Visit (approximately 8 to 11 hours)

Secondary Outcome Measure Information:

Title

Maximum Change in GIR (Glucose Infusion Rate) From Baseline

Description

Time Frame

1 Day Visit (approximately 8 to 11 hours)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Steven J Russell, MD, PhD

Organizational Affiliation

Massachusetts General Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Massachusetts General Hospital Diabetes Research Center

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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

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