Type 1 Diabetes Mellitus
Conditions
Keywords
Type 1 Diabetes, Bionic Pancreas, Artificial Pancreas, Insulin, Glucagon, Alcohol, Alcohol Clamp
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.
Interventions
DRUGEthanol
IV infusion of ethanol to stabilize BAC (blood alcohol content) at 0.1%
DRUGGlucagon
injection of 50 micrograms of glucagon
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 80 Years
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AOCGIR (Area Over the Curve for Glucose Infusion Rate) | 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
| Measure | Time frame | Description |
|---|---|---|
| Maximum Change in GIR (Glucose Infusion Rate) From Baseline | 1 Day Visit (approximately 8 to 11 hours) | 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. |
Countries
United States
Participant flow
Pre-assignment details
26 subjects were enrolled. 8 subjects were ineligible to participate, 1 subject withdrew consent, and 2 subjects were not able to be scheduled to participate. 15 subjects participated in both visits.
Participants by arm
| Arm | Count |
|---|---|
| All Subjects All subjects enrolled | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | All Subjects |
|---|---|
| Age, Continuous | 39.3 years STANDARD_DEVIATION 17.4 |
| Diabetes Duration | 28.4 years STANDARD_DEVIATION 17.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 3 / 15 | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
Outcome results
Primary
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%
Time frame: 1 Day Visit (approximately 8 to 11 hours)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glucagon With Ethanol | AOCGIR (Area Over the Curve for Glucose Infusion Rate) | 1996 mg*minute/dl | Standard Deviation 1259 |
| Glucagon Without Ethanol | AOCGIR (Area Over the Curve for Glucose Infusion Rate) | 1981 mg*minute/dl | Standard Deviation 938 |
Secondary
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.
Time frame: 1 Day Visit (approximately 8 to 11 hours)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glucagon With Ethanol | Maximum Change in GIR (Glucose Infusion Rate) From Baseline | 83.0 ml/hour | Standard Deviation 35.2 |
| Glucagon Without Ethanol | Maximum Change in GIR (Glucose Infusion Rate) From Baseline | 101.7 ml/hour | Standard Deviation 38.8 |