Trial Outcomes & Findings for Mechanisms of Hypoglycemia Associated Autonomic Failure (NCT NCT00678145)

Zero (0) Type 1 Diabetes (T1D) patients were enrolled into the study. All study participants were healthy individuals without diabetes who were not on medication and had no history of hypoglycemia or family history of diabetes. One participant in the Naloxone vs Placebo comparator crossover study consented but was not enrolled. As such, 17 participants were enrolled into that study.

Age data was not documented from three (3) participants at baseline for the Naloxone vs Placebo comparator crossover study.

EGP response after antecedent morphine administration was assessed in the Morphine Sulfate vs Matched Placebo study. EGP response is a measure of how the body produces glucose from substrates to maintain blood sugar levels, particularly during fasting. Morphine was administered on Day 1 followed by a stepped hypoglycemia clamp (i.e., euglycemia → 90 mg/dl → 80 mg/dl → 70 mg/dl → 60 mg/dl) on Day 2. EGP response rate is reported in milligrams/kilograms/minute (mg/kg/min) and results are summarized and reported by study arm using basic descriptive statistics. Data from the final hour of the 3rd clamp episode were averaged/reported.

For the Naloxone vs Matched Placebo study, EGP, a measure of the body's production of sugar, was assessed by determining the Glucose Infusion Rate (GIR) an indirect measure of endogenous glucose production, during the first and third hypoglycemic clamp episodes. GIR is reported in cubic centimeters/minute (cc/min) and results are summarized and reported by study arm using basic descriptive statistics.

EGP response after antecedent epinephrine administration was assessed in the Epinephrine vs Matched Epinephrine study. EGP response, a measure of how the body produces glucose from substrates to maintain blood sugar levels, was assessed during the final hypoglycemic clamp episode. EGP at the major nadir at the 60 mg/dL, during the last 10 minutes of the 3rd clamp episode, is reported in milligrams per kilogram per minute (mg/kg/min) and results are summarized and reported by study arm using basic descriptive statistics. Data from the final hour of the 3rd clamp episode were averaged/reported

Counterregulatory response to hypoglycemia was assessed for the Morphine Sulfate study by quantifying peak plasma responses to three episodes of induced hypoglycemia over two days: two, 2-hour episodes of moderate hyper-insulinemic, hypoglycemic clamp studies (target glucose 54 mg/dL), separated by a 2-hour break with a small snack, on Day 1, followed by a third, comparable hypoglycemic episode on Day 2. Group mean results are summarized for the Morphine Sulfate arm and Matched Placebo arm.

Counterregulatory response to hypoglycemia was assessed for the Naloxone study by quantifying peak plasma responses to three episodes of induced hypoglycemia over two days: two, 2-hour episodes of moderate hyper-insulinemic, hypoglycemic clamp studies (target glucose 54 mg/dL), separated by a 2-hour break with a small snack, on Day 1, followed by a third, comparable hypoglycemic episode on Day 2. The second challenge on Day 1 was conducted to assess the impact of the third episode for informational purposes only but was not reported. Group mean results are summarized for the 1st and 3rd episodes in the Naloxone arm and Matched Placebo arm.

Counterregulatory response to hypoglycemia was assessed for the Epinephrine study by quantifying peak plasma epinephrine level responses to three episodes of induced hypoglycemia over two days: two, 2-hour episodes of moderate hyper-insulinemic, hypoglycemic clamp studies (target glucose 60 mg/dL), separated by a 2-hour break with a small snack, on Day 1, followed by a third, comparable hypoglycemic episode on Day 2. Group mean results are summarized for the Epinephrine arm and Matched Placebo arm.

Hypoglycemic Symptom Scores were evaluated using the Edinburgh Hypoglycemia Symptom Scale (EHSS). The EHSS is an instrument to evaluate patients' experiences of symptoms in a typical hypoglycemic episode. It is comprised of 11 symptoms within 3 domains: Neuroglycopenic (i.e., confusion, drowsiness, odd behavior, speech difficulty, and incoordination), Autonomic (i.e., sweating, palpitations, shaking, and hunger), and General Malaise (i.e., headaches, nausea); which are evaluated by a 8-point Likert scale ranging from 0 = "Not at all" to 7 = "Very severely." An overall global mean composite score for the 11 symptoms was summed and averaged for each participant during the 3rd hypoglycemic episode on Day 2. Higher scores are indicative of more EHSS symptoms. Group mean values will be reported using basic descriptive statistics.

Hypoglycemic Symptom Scores were evaluated using the Edinburgh Hypoglycemia Symptom Scale (EHSS). The EHSS is an instrument to evaluate patients' experiences of symptoms in a typical hypoglycemic episode. It is comprised of 11 symptoms within 3 domains: Neuroglycopenic (i.e., confusion, drowsiness, odd behavior, speech difficulty, and incoordination), Autonomic (i.e., sweating, palpitations, shaking, and hunger), and General Malaise (i.e., headaches, nausea); which are evaluated by a 8-point Likert scale ranging from 0 = "Not at all", to 7 = "Very severely." An overall global mean composite score for the 11 symptoms was summed and averaged for each participant during the 3rd hypoglycemic episode on Day 2. Higher scores are indicative of more EHSS symptoms. Group mean values will be reported using basic descriptive statistics.

Hypoglycemic Symptom Scores were evaluated using the Edinburgh Hypoglycemia Symptom Scale (EHSS). The EHSS is an instrument to evaluate patients' experiences of symptoms in a typical hypoglycemic episode. It is comprised of 11 symptoms within 3 domains: Neuroglycopenic (i.e., confusion, drowsiness, odd behavior, speech difficulty, and incoordination), Autonomic (i.e., sweating, palpitations, shaking, and hunger), and General Malaise (i.e., headaches, nausea); which are evaluated by a 7-point Likert scale ranging from 1 = "Not at all", to 7 = "Very severely." An overall global mean composite score for the 11 symptoms was summed and averaged for each participant during the 3rd hypoglycemic episode on Day 2. Higher scores are indicative of more EHSS symptoms. Group mean values will be reported using basic descriptive statistics.