Intra-nasal Naloxone for Treatment of Impaired Awareness of Hypoglycemia

This is a single center, single-blind randomized cross over design trial that will compare the impact of intra-nasal naloxone vs. intra-nasal saline administration during experimental hypoglycemia on day one on responses to experimental hypoglycemia on day two. Investigators intend to enroll 18 individuals to obtain the complete data sets from 15 participants. Expected duration of subject participation is 10-12 weeks. This study will consist of two 2-day intervention visits separated by approximately 8 weeks.

Study Overview

• Status: Terminated
• Conditions: Type 1 Diabetes; Hypoglycemia Unawareness
• Intervention / Treatment: Drug: Intra-nasal saline; Drug: intra-nasal naloxone

Detailed Description

This is a single center, single-blinded randomized cross over design trial, that will compare the impact of IN naloxone vs. IN saline during experimental hypoglycemia on day one on the responses to experimental hypoglycemia on day two. 18 participants will be studied twice, 8 weeks apart. On each occasion participants will undergo a 2 hour hypoglycemic clamp (target 50 mg/dl) in the morning and in the afternoon on day one and then again on the morning of day 2. During the morning clamps, samples will be collected for later measurement of serum epinephrine, glucagon and cortisol levels and participants will be asked to complete a hypoglycemia symptom questionnaire. 3 intranasal doses (4 mg each) of naloxone hydrochloride or IN saline will be administered to the subject on day 1. Plasma will be collected for measurement of naloxone concentrations on day 1 primary outcome is the difference in peak epinephrine secretion during the morning episodes of hypoglycemia on days one and two, thus each participant will have two observations: one from their naloxone experiment and one from their saline experiment.

Secondary endpoint will be naloxone pharmacokinetics including maximum concentration (Cmax), time to maximum concentration (Tmax) and area under the curve (AUC)

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55446
      • Clinical and Translational Science Institute, University of Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects are capable of giving informed consent.
2. Female subjects must be post-menopausal for at least 1 year, or surgically incapable of bearing children, or practicing at least one or more of the following methods of contraception for three months prior to, and during the study: hormonal, intrauterine device (IUD), or barrier method in combination with a spermicide.
3. Subject should be medication free, other than hormonal birth control, for 48 hours before through 24 hours after study drug administration. If the need for medication is identified during this time period, it will be discussed with and approved by the PI.

Exclusion Criteria:

1. Women who are pregnant.
2. Women who are breastfeeding.
3. Subject has a known hypersensitivity to naloxone.
4. Subject with hypertension
5. Subject has a significant history of cardiac, neurologic, psychiatric, oncologic, endocrine, metabolic, renal or hepatic disease
6. Subject has taken or used any investigational drug or device in the 30 days prior to screening.
7. Subject has taken either prescribed or over the counter medication for 48 hours prior to study drug administration on either of the study days, other than hormonal birth control.
8. History of narcotic or heroin abuse.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 3 doses of intra-nasal saline will be given during controlled hypoglycemic insulin clamps	Drug: Intra-nasal saline; 3 doses of intra-nasal saline will be given during controlled hypoglycemic insulin clamps
Experimental: Treatment with intra-nasal Naloxone; 3 doses of intra-nasal naloxone (4 mg each) will be given during controlled hypoglycemic insulin clamps	Drug: intra-nasal naloxone; 3 doses of intra-nasal naloxone (4 mg each) will be given during controlled hypoglycemic insulin clamps; Other Names: Narcan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Within Person Difference in Peak Epinephrine During Hypoglycemia	Primary endpoint will be the within person difference in peak epinephrine secretion during the morning episodes of hypoglycemia on days one and two; investigators will compare this difference between the two treatment conditions	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Naloxone Pharmacokinetics	maximum concentration (Cmax)	2 year
Naloxone Pharmacokinetics	area under the curve (AUC)	2 year

Collaborators and Investigators

• Sponsor: University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2016
• Primary Completion (Actual): July 1, 2021
• Study Completion (Actual): July 1, 2021

Study Registration Dates

• First Submitted: February 24, 2016
• First Submitted That Met QC Criteria: March 1, 2016
• First Posted (Estimate): March 7, 2016

Study Record Updates

• Last Update Posted (Actual): March 27, 2023
• Last Update Submitted That Met QC Criteria: March 24, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: hypoglycemia; type 1 diabetes; hypoglycemia unawareness
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Nervous System Diseases; Immune System Diseases; Autoimmune Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Endocrine System Diseases; Diabetes Mellitus; Consciousness Disorders; Diabetes Mellitus, Type 1; Hypoglycemia; Unconsciousness; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Naloxone
• Other Study ID Numbers: 1103M96932

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No