Novel Approach for the Prevention of Hypoglycemia Associated Autonomic Failure (HAAF)
Diabetes Mellitus, Type 1, Hypoglycemia, Hypoglycemia Unawareness
About this trial
This is an interventional prevention trial for Diabetes Mellitus, Type 1 focused on measuring diabetes, hypoglycemia, diazoxide, naloxone, healthy subjects, low blood sugar
Eligibility Criteria
Inclusion Criteria:
-Healthy, non-diabetic subjects 21-55 years old
Exclusion Criteria:
- BMI >35kg/m2
- BP >150/90 or <90/60 on repeated measurements and on more than one occasion
- Triglycerides >400 mg/dL and/or total cholesterol >300 mg/dL
- Clinically significant liver dysfunction
- Clinically significant kidney dysfunction
- Clinically significant anemia
- Clinically significant leukocytosis or leukopenia
- Clinically significant thrombocytopenia or thrombocytosis
- Positive drug screen for amphetamines, barbiturates, benzodiazepines, cocaine, methadone, opiates, oxycodone, PCP
- Currently taking beta-blockers or medications that affect counterregulatory response to hypoglycemia
- Urinalysis: clinically significant abnormalities
- Clinically significant electrolyte abnormalities
- Smoking >10 cigarettes/day
- Heavy alcohol use
- History of chronic conditions (eg, chronic liver disease, cardiovascular disease, bleeding disorders, cancer, HIV/AIDS, seizures, systemic rheumatologic conditions)
- Surgeries involving endocrine glands
- Pregnancy
- Enrollment in another medication intervention study less than one month prior, besides those done by our group
- Family history of diabetes or premature cardiac death in first degree relatives
- Allergies to medications given during study
- Uncontrolled psychiatric disorders
Sites / Locations
- Albert Einstein College of Medicine
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
No Intervention
Experimental
Placebo Comparator
Experimental
Active Comparator
Active Comparator
Placebo Comparator
No intervention (Susceptibility to HAAF evaluation)
Naloxone
Placebo (for Naloxone)
Naloxone + diazoxide
Diazoxide + placebo (for naloxone)
Naloxone + placebo (for diazoxide)
Placebo (for naloxone) + placebo (for diazoxide)
Susceptibility to HAAF evaluation: No intervention medication will be given during episodes of hypoglycemia.
Naloxone evaluation: Intranasal naloxone (4 mg NARCAN Nasal Spray) via a nostril twice during the first hypoglycemia episode; once at the start of insulin administration and again after one hour. Intranasal naloxone (4 mg NARCAN Nasal Spray) will again be given via a nostril twice during the second period of hypoglycemia; once at the start of insulin administration and again after one hour.
Naloxone evaluation: Placebo (for naloxone) nasal spray via a nostril twice during the first hypoglycemia episode; once at the start of insulin administration and again after one hour. Placebo (for naloxone) nasal spray will again be given via a nostril twice during the second period of hypoglycemia; once at the start of insulin administration and again after one hour.
Naloxone/Diazoxide evaluation: Up to 7 mg/kg oral diazoxide 3 hours before the first hypoglycemic episode. Intranasal naloxone (4 mg NARCAN Nasal Spray) via a nostril twice during the first hypoglycemia episode; once at the start of insulin administration and again after one hour. Intranasal naloxone (4 mg NARCAN Nasal Spray) will again be given via a nostril twice during the second period of hypoglycemia; once at the start of insulin administration and again after one hour.
Naloxone/Diazoxide evaluation: Up to 7 mg/kg oral diazoxide 3 hours before the first hypoglycemic episode. Placebo (for naloxone) nasal spray via a nostril twice during the first hypoglycemia episode; once at the start of insulin administration and again after one hour. Placebo (for naloxone) nasal spray will again be given via a nostril twice during the second period of hypoglycemia; once at the start of insulin administration and again after one hour.
Naloxone/Diazoxide evaluation: Oral placebo (for diazoxide) 3 hours before the first hypoglycemic episode. Intranasal naloxone (4 mg NARCAN Nasal Spray) via a nostril twice during the first hypoglycemia episode; once at the start of insulin administration and again after one hour. Intranasal naloxone (4 mg NARCAN Nasal Spray) will again be given via a nostril twice during the second period of hypoglycemia; once at the start of insulin administration and again after one hour.
Naloxone/Diazoxide evaluation: Oral placebo (for diazoxide) 3 hours before the first hypoglycemic episode. Placebo (for naloxone) nasal spray via a nostril twice during the first hypoglycemia episode; once at the start of insulin administration and again after one hour. Placebo (for naloxone) nasal spray will again be given via a nostril twice during the second period of hypoglycemia; once at the start of insulin administration and again after one hour.