search
Back to results

Naloxone, Hypoglycemia and Exercise

Primary Purpose

Diabetes Mellitus, Type 1

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Naloxone then placebo
Placebo then Naloxone
Sponsored by
University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 1

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • University of Minnesota

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

1

2

Arm Description

Naloxone, then placebo

Placebo, then Naloxone

Outcomes

Primary Outcome Measures

Change in Symptom Score
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
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.

Secondary Outcome Measures

Full Information

First Posted
May 9, 2017
Last Updated
July 26, 2023
Sponsor
University of Minnesota
search

1. Study Identification

Unique Protocol Identification Number
NCT03149770
Brief Title
Naloxone, Hypoglycemia and Exercise
Official Title
Hypoglycemia After Exercise in Type 1 Diabetes: Intranasal Naloxone as a Novel Therapy to Preserve Hypoglycemia Counterregulation
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
September 18, 2017 (Actual)
Primary Completion Date
May 1, 2022 (Actual)
Study Completion Date
April 1, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Minnesota

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
36 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
Naloxone, then placebo
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
Placebo, then Naloxone
Intervention Type
Drug
Intervention Name(s)
Naloxone then placebo
Intervention Description
naloxone intranasal 4mg, then placebo
Intervention Type
Drug
Intervention Name(s)
Placebo then Naloxone
Intervention Description
placebo then naloxone intranasal 4mg
Primary Outcome Measure Information:
Title
Change in Symptom Score
Description
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.
Time Frame
Day 2
Title
Change in Epinephrine Levels
Description
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.
Time Frame
Day 2

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Elizabeth Seaquist, MD
Organizational Affiliation
University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Naloxone, Hypoglycemia and Exercise

We'll reach out to this number within 24 hrs