Intra-nasal Naloxone for Treatment of Impaired Awareness of Hypoglycemia

• ClinicalTrials.gov Identifier: NCT02700048
• Recruitment Status: Active, not recruiting
• First Posted: March 7, 2016
• Last Update Posted: January 27, 2021
• Sponsor: University of Minnesota
• Information provided by (Responsible Party): University of Minnesota

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Hypoglycemia Unawareness; Type 1 Diabetes	Drug: intra-nasal naloxone; Drug: Intra-nasal saline	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Prevention
• Official Title: Intra-nasal Naloxone for Treatment of Impaired Awareness of Hypoglycemia
• Study Start Date: June 2016
• Estimated Primary Completion Date: November 2021
• Estimated Study Completion Date: December 2021

Arms and Interventions

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 Name: Narcan

Outcome Measures

Primary Outcome Measures :

1. within person difference in peak epinephrine during hypoglycemia [ Time Frame: 2 years ]
   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

Secondary Outcome Measures :

1. naloxone pharmacokinetics [ Time Frame: 2 year ]
   maximum concentration (Cmax)
2. naloxone pharmacokinetics [ Time Frame: 2 year ]
   area under the curve (AUC)

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Minnesota

Clinical and Translational Science Institute, University of Minnesota

Minneapolis, Minnesota, United States, 55446

Sponsors and Collaborators

University of Minnesota

Investigators

• Principal Investigator: Amir Moheet, MD; University of Minnesota

More Information

• Responsible Party: University of Minnesota
• ClinicalTrials.gov Identifier: NCT02700048
• Other Study ID Numbers: 1103M96932
• First Posted: March 7, 2016
• Last Update Posted: January 27, 2021
• Last Verified: January 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Minnesota:

type 1 diabetes; hypoglycemia; hypoglycemia unawareness

Additional relevant MeSH terms:

Unconsciousness; Diabetes Mellitus, Type 1; Hypoglycemia; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Consciousness Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Naloxone; Narcotic Antagonists; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents