Hypoglycemia
Conditions
Keywords
Hypoglycemia, Type 1 diabetes
Brief summary
Insulin treatment often causes the blood glucose levels to fall too low. The body usually responds to low blood glucose levels by releasing hormones which act against the insulin to help correct the low blood glucose levels. However, this hormone response can be altered in people with diabetes. Currently there are no therapeutic agents that can be used to improve the recovery from hypoglycemia (low blood sugar). Naltrexone is a tablet used to help people who are addicted to alcohol or morphine-based drugs to remain drug and alcohol-free but it can also affect the levels of the hormones which are released during hypoglycemia. The aim of this study is to determine whether naltrexone can be used to improve and accelerate the recovery from hypoglycemia in patients with type 1 diabetes.
Interventions
DRUGNaltrexone High Dose
Naltrexone 100mg for two administrations.
DRUGNaltrexone Low Dose
Naltrexone 50mg for two administrations.
Sponsors
National Institutes of Health (NIH)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* type 1 diabetes (well controlled, 2-3 hypoglycemic episodes/wk) age 18-55, BMI 18-35
Exclusion criteria
* pregnancy * significant diabetes complications * liver disease, cirrhosis * cardiac disease * neurological disorder * autonomic neuropathy * kidney disease * lactose intolerance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glucose (mg/dL) | End of study (up to 240 minutes) | Glucose was measured in the blood throughout the hyperinsulinemic-hypoglycemic clamp study. |
| Glucose Infusion Rate (mg/kg.Min) | End of study (up to 240 minutes) | The glucose infusion rate corresponds to the amount of 20% dextrose given during the hyperinsulinemic-hypoglycemic clamp study, necessary to keep blood glucose levels at the target range (50-55 mg/dL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glucagon (pg/mL) | End of study (up to 240 minutes) | Glucagon was measured in the blood throughout the hyperinsulinemic-hypoglycemic clamp study. |
| Cortisol (ug/dL) | End of study (up to 240 minutes) | Cortisol was measured in the blood throughout the hyperinsulinemic-hypoglycemic clamp study. |
| Epinephrine (pg/mL) | End of study (up to 240 minutes) | Epinephrine was measured in the blood throughout the hyperinsulinemic-hypoglycemic clamp study. |
| Norepinephrine (pg/mL) | End of study (up to 240 minutes) | Norepinephrine was measured in the blood throughout the hyperinsulinemic-hypoglycemic clamp study. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Naltrexone (Lower Dose) Naltrexone: Naltrexone 50 mg, 1 tablet given every 12 hours orally | 4 |
| Naltrexone (Higher Dose) Naltrexone: Naltrexone 100mg, 1 tablet given every 12 hours orally | 10 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Second Assignment | Lost to Follow-up | 1 | 0 | 0 | 0 |
| Second Assignment | Protocol Violation | 0 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Naltrexone (Lower Dose) | Naltrexone (Higher Dose) | Total |
|---|---|---|---|
| Age, Continuous | 32.3 years STANDARD_DEVIATION 11 | 32.4 years STANDARD_DEVIATION 12 | 32.4 years STANDARD_DEVIATION 11 |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 6 Participants |
| Sex: Female, Male Male | 2 Participants | 6 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 4 | 0 / 4 | 5 / 10 | 3 / 10 |
| serious Total, serious adverse events | 0 / 4 | 0 / 4 | 0 / 10 | 0 / 10 |
Outcome results
Primary
Glucose Infusion Rate (mg/kg.Min)
The glucose infusion rate corresponds to the amount of 20% dextrose given during the hyperinsulinemic-hypoglycemic clamp study, necessary to keep blood glucose levels at the target range (50-55 mg/dL).
Time frame: End of study (up to 240 minutes)
Population: Subjects' data were pooled and only those that completed both visits are analyzed here.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Naltrexone (Lower Dose) | Glucose Infusion Rate (mg/kg.Min) | Active Drug | 4.6 mg/kg.min | Standard Deviation 2.7 |
| Naltrexone (Lower Dose) | Glucose Infusion Rate (mg/kg.Min) | Placebo | 4.8 mg/kg.min | Standard Deviation 4 |
| Naltrexone (Higher Dose) | Glucose Infusion Rate (mg/kg.Min) | Active Drug | 6.3 mg/kg.min | Standard Deviation 2.4 |
| Naltrexone (Higher Dose) | Glucose Infusion Rate (mg/kg.Min) | Placebo | 5.9 mg/kg.min | Standard Deviation 2.7 |
Primary
Glucose (mg/dL)
Glucose was measured in the blood throughout the hyperinsulinemic-hypoglycemic clamp study.
Time frame: End of study (up to 240 minutes)
Population: Subjects' data were pooled and only those that completed both visits are analyzed here.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Naltrexone (Lower Dose) | Glucose (mg/dL) | Active Drug | 56.5 mg/dL | Standard Deviation 3.7 |
| Naltrexone (Lower Dose) | Glucose (mg/dL) | Placebo | 55.0 mg/dL | Standard Deviation 2.8 |
| Naltrexone (Higher Dose) | Glucose (mg/dL) | Active Drug | 52.8 mg/dL | Standard Deviation 8.6 |
| Naltrexone (Higher Dose) | Glucose (mg/dL) | Placebo | 52.8 mg/dL | Standard Deviation 8.6 |
Secondary
Cortisol (ug/dL)
Cortisol was measured in the blood throughout the hyperinsulinemic-hypoglycemic clamp study.
Time frame: End of study (up to 240 minutes)
Population: Subjects' data were pooled and only those that completed both visits are analyzed here.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Naltrexone (Lower Dose) | Cortisol (ug/dL) | Active Drug | 22.9 ug/dL | Standard Deviation 8.3 |
| Naltrexone (Lower Dose) | Cortisol (ug/dL) | Placebo | 16.0 ug/dL | Standard Deviation 7 |
| Naltrexone (Higher Dose) | Cortisol (ug/dL) | Active Drug | 16.4 ug/dL | Standard Deviation 8.1 |
| Naltrexone (Higher Dose) | Cortisol (ug/dL) | Placebo | 15.2 ug/dL | Standard Deviation 5.2 |
Secondary
Epinephrine (pg/mL)
Epinephrine was measured in the blood throughout the hyperinsulinemic-hypoglycemic clamp study.
Time frame: End of study (up to 240 minutes)
Population: Subjects' data were pooled and only those that completed both visits are analyzed here.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Naltrexone (Lower Dose) | Epinephrine (pg/mL) | Active Drug | 92.75 pg/mL | Standard Deviation 30.6 |
| Naltrexone (Lower Dose) | Epinephrine (pg/mL) | Placebo | 42.75 pg/mL | Standard Deviation 23.1 |
| Naltrexone (Higher Dose) | Epinephrine (pg/mL) | Active Drug | 126.1 pg/mL | Standard Deviation 98 |
| Naltrexone (Higher Dose) | Epinephrine (pg/mL) | Placebo | 77.9 pg/mL | Standard Deviation 65.8 |
Secondary
Glucagon (pg/mL)
Glucagon was measured in the blood throughout the hyperinsulinemic-hypoglycemic clamp study.
Time frame: End of study (up to 240 minutes)
Population: Subjects' data were pooled and only those that completed both visits are analyzed here.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Naltrexone (Lower Dose) | Glucagon (pg/mL) | Active Drug | 44.1 pg/mL | Standard Deviation 17.4 |
| Naltrexone (Lower Dose) | Glucagon (pg/mL) | Placebo | 40.4 pg/mL | Standard Deviation 7.9 |
| Naltrexone (Higher Dose) | Glucagon (pg/mL) | Active Drug | 48.9 pg/mL | Standard Deviation 16.5 |
| Naltrexone (Higher Dose) | Glucagon (pg/mL) | Placebo | 53.6 pg/mL | Standard Deviation 16.4 |
Secondary
Norepinephrine (pg/mL)
Norepinephrine was measured in the blood throughout the hyperinsulinemic-hypoglycemic clamp study.
Time frame: End of study (up to 240 minutes)
Population: Subjects' data were pooled and only those that completed both visits are analyzed here.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Naltrexone (Lower Dose) | Norepinephrine (pg/mL) | Active Drug | 248.3 pg/mL | Standard Deviation 80.2 |
| Naltrexone (Lower Dose) | Norepinephrine (pg/mL) | Placebo | 282.8 pg/mL | Standard Deviation 97.3 |
| Naltrexone (Higher Dose) | Norepinephrine (pg/mL) | Placebo | 217.1 pg/mL | Standard Deviation 91.5 |
| Naltrexone (Higher Dose) | Norepinephrine (pg/mL) | Active Drug | 200.1 pg/mL | Standard Deviation 77.4 |