Naloxone, Hypoglycemia and Exercise

Sponsor

University of Minnesota (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03149770

Collaborator

(none)

Enrollment

Location

Arms

63.4

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The overall objective of this project is to determine if the intranasal administration of naloxone during exercise will be a novel approach to preserve the counterregulatory response to hypoglycemia experienced the next day in patients with type 1 diabetes. Exercise induced autonomic failure contributes to the development of impaired awareness of hypoglycemia. Treatments that blunt the consequences of exercise induced autonomic failure, such as preserving the post-exercise counterregulatory response to hypoglycemia, may improve awareness of hypoglycemia. Naloxone, an opioid antagonist, is an extremely promising agent. In healthy volunteers, intravenous administration of naloxone during exercise preserved the counterregulatory response to hypoglycemia the following day (1). In this study, investigators will extend the clinical applicability by administering intranasal naloxone to individuals with type 1 diabetes. Specifically, the investigators will use a randomized, placebo controlled, crossover design to administer drug or placebo to patients with type 1 diabetes during acute exercise and assess the counterregulatory response to hypoglycemia the following day. The use of intranasal naloxone is a highly innovative aspect of this proposal. Intranasal naloxone translates readily to clinical use and, as demonstrated by the investigators preliminary data, achieves similar plasma drug concentrations as after IV administration.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1	Drug: Naloxone Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

36 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Hypoglycemia After Exercise in Type 1 Diabetes: Intranasal Naloxone as a Novel Therapy to Preserve Hypoglycemia Counterregulation

Actual Study Start Date :

Sep 18, 2017

Actual Primary Completion Date :

May 1, 2022

Anticipated Study Completion Date :

Dec 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Naloxone, intranasal 4mg	Drug: Naloxone naloxone vs placebo
Placebo Comparator: 2 Placebo	Drug: Placebo placebo vs naloxone

Arm

Intervention/Treatment

Experimental: 1

Naloxone, intranasal 4mg

Drug: Naloxone

naloxone vs placebo

Placebo Comparator: 2

Placebo

Drug: Placebo

placebo vs naloxone

Outcome Measures

Primary Outcome Measures

Change in Symptom Score [Day 2]
The primary outcome variable for Aim 1 will be the difference, naloxone vs. saline, in symptom scores collected using a standard questionnaire during the hypoglycemic clamp on Day 2, after administration of intranasal treatment during exercise on Day 1.
Change in Epinephrine Levels [Day 2]
The primary outcome variable for Aim 2 will be the difference, naloxone vs. saline, in peak epinephrine levels measured during the hypoglycemic clamp on Day 2, after administration of treatment during exercise on Day 1.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Type 1 diabetes diagnosed on clinical grounds (history of DKA, use of insulin within 6 months of diagnosis)
Diabetes duration < 30 years (impaired awareness of hypoglycemia increases with duration so it will be more likely that shorter duration participants will have hypoglycemia awareness) but > 2 years (to ensure that they have lost hypoglycemia induced glucagon secretion as is typical in patients who develop impaired awareness of hypoglycemia)
Age 18 - 65 years
Baseline hemoglobin A1C 6.8 - 9.0% (range selected to reduce the risk of hypoglycemia and uncontrolled diabetes in the weeks before the study, both of which may affect the responses to hypoglycemia)
Awareness of hypoglycemia as verified by Cox questionnaire

Exclusion Criteria:

History of stroke, seizures (other than those related to hypoglycemia), arrhythmias, active cardiac disease
History of hypertension or blood pressure > 140/95 mm Hg at screening visit
Pregnancy or plan to become pregnant during the study period
Health related limitations in exercise (including but not limited to: angina, uncontrolled asthma, peripheral arterial disease)
Unwillingness to avoid exercise during the 7 days before each part of the study
Concomitant medical problems that may prevent the participant from successfully completing the protocol
Smoking as defined by 2 or more tobacco cigarettes a week
Daily use of opioids or an opioid antagonist or use in the past two weeks
Unwillingness to wear a continuous glucose monitor for one week before and one week after each part of the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Minnesota	Minneapolis	Minnesota	United States	55455

Sponsors and Collaborators

University of Minnesota

Investigators

Principal Investigator: Elizabeth Seaquist, MD, University of Minnesota

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

University of Minnesota

ClinicalTrials.gov Identifier:

NCT03149770

Other Study ID Numbers:

MED-2017-25555

First Posted:

May 11, 2017

Last Update Posted:

Jun 22, 2022

Last Verified:

Jun 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Hypoglycemia

Diabetes Mellitus, Type 1

Naloxone

Study Results

No Results Posted as of Jun 22, 2022