The Use of Mini-dose Glucagon to Prevent Exercise-induced Hypoglycemia in Type 1 Diabetes

February 28, 2020 updated by: Jaeb Center for Health Research
This project focuses on development of new strategy for the prevention of exercise-associated hypoglycemia using mini-dose glucagon.

Study Overview

Detailed Description

The primary objective of the protocol is to determine if the administration of mini-dose glucagon administered subcutaneously just before exercise produces better glucose stability than no adjustments for moderate intensity exercise in patients with Type 1 Diabetes (T1D). It will also be assessed whether mini-dose glucagon before exercise produces better glucose stability than basal insulin reductions or extra carbohydrate consumption.

This is a randomized, 4-way crossover trial. The trial will include 16 participants who complete the study.

Each participant will undergo four aerobic exercise sessions (in random order), with different strategies for glucose regulation:

  • Control Trial: Fasted exercise, no basal insulin reduction
  • Strategy 1: Fasted exercise, basal insulin reduction only (50% reduction in basal rate at 60 minutes before exercise, for the duration of the exercise)
  • Strategy 2: Fasted exercise, no basal adjustment + pre-exercise glucose tabs (buccal route-40 grams in total )
  • Strategy 3: Fasted exercise, no basal adjustment + pre-exercise mini-dose glucagon (sc)

In all 4 sessions, aerobic exercise will be performed in the fasted state (before a standardized meal) for 45 minuets at ~50-55% of the participant's per-determined aerobic capacity. The participant's pump will be blinded during the control trial, strategy 1, and strategy 3 and an injection of saline will be given during the control trial and strategy 1 so that participant is blinded to strategy.

The primary outcome for this study will be the glycemic response during exercise and early recovery.

Study Type

Interventional

Enrollment (Actual)

16

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Joslin Diabetes Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 64 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Clinical diagnosis of presumed autoimmune type 1 diabetes, receiving daily insulin
  2. Age 18-<65 years
  3. Duration of T1D ≥ 2 years
  4. Random C-peptide < 0.6 ng/ml
  5. Using continuous subcutaneous insulin infusion (CSII; insulin pump) for at least 6 months, with no plans to discontinue pump use during the study
  6. Exercises regularly, i.e. ≥30 minutes moderate or more vigorous aerobic activity X ≥3 times/week
  7. Body mass index (BMI) <30 kg/m2
  8. Females must meet one of the following criteria:

    • Of childbearing potential and not currently pregnant or lactating, and agrees to use an accepted contraceptive regimen as described in the study procedure manual throughout the entire duration of the study; or
    • Of non-childbearing potential, defined as a female who has had a hysterectomy or tubal ligation, is clinically considered infertile or is in a menopausal state (at least 1 year without menses)
  9. In good general health with no conditions that could influence the outcome of the trial, and in the judgment of the investigator is a good candidate for the study based on review of available medical history, physical examination and clinical laboratory evaluations
  10. Willing to adhere to the protocol requirements for the duration of the study
  11. Must be enrolled in the T1D Exchange clinic registry or willing to join the registry

Exclusion Criteria:

  1. One or more severe hypoglycemic episodes in the past 12 months (as defined by an episode that required third party assistance for treatment)
  2. Active diabetic retinopathy (proliferative diabetic retinopathy or vitreous hemorrhage in past 6 months) that could potentially be worsened by exercise protocol
  3. Peripheral neuropathy with insensate feet
  4. Cardiovascular autonomic neuropathy with inappropriate heart rate response to exercise
  5. Use of non-insulin anti-diabetic medications
  6. Use of beta-blockers
  7. Use of agents that affect hepatic glucose production such as beta adrenergic agonists, xanthine derivatives
  8. Use of Pramlintide
  9. Currently following a very low calorie or other weight-loss diet
  10. Participation in other studies involving administration of an investigational drug or device within 30 days or 5 half-lives, whichever is longer, before screening for the current study or planning to participate in another such study during participation in the current study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Control
No basal insulin adjustment, no carbohydrate intake (until glucose drops <70 mg/dL).
Active Comparator: Basal insulin reduction
Basal insulin reduction to 50% five minutes before the start of exercise.
Basal insulin reduction to 50% 5 minutes before the start of exercise.
Active Comparator: Glucose Tabs
Dextrose tabs orally (20 grams) five minutes before the start of exercise and at 30 minutes of exercise (total 40 grams).
Dextrose tabs orally (20 grams) 5 minutes before the start of exercise and at 30 minutes of exercise (total 40 grams).
Other Names:
  • over-the-counter oral glucose tablets
Experimental: G-Pen Mini™ (glucagon injection)
Glucagon (150 µg) five minutes before the start of exercise (SQ-abdomen).
Glucagon (150 µg) 5 minutes before the start of exercise (SQ-abdomen).
Other Names:
  • mini-dose glucagon

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Glycemic Response During Exercise and Early Recovery
Time Frame: 0 to 75 minutes following exercise initiation (0, 5, 10, 15, 25, 35, 45, 50, 55, 60, 75 min)
Comparison of glycemic response (from blood glucose) during exercise and early recovery between each exercise strategy.
0 to 75 minutes following exercise initiation (0, 5, 10, 15, 25, 35, 45, 50, 55, 60, 75 min)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Hypoglycemia (<70 mg/dL) During Exercise and Early Recovery
Time Frame: 0 to 75 minutes following exercise initiation
Comparison of occurrence of hypoglycemia (<70 mg/dL from blood glucose) during exercise and early recovery between each exercise strategy.
0 to 75 minutes following exercise initiation
Number of Participants With Hyperglycemia (≥250 mg/dL) During Exercise and Early Recovery
Time Frame: 0 to 75 minutes following exercise initiation
Comparison of occurrence of hyperglycemia (≥250 mg/dL from blood glucose) during exercise and early recovery between each exercise strategy.
0 to 75 minutes following exercise initiation
Continuous Glucose Monitor (CGM) Metrics During Late Recovery - Nadir Glucose
Time Frame: 90 min after the standard meal until 1200 noon the day after each exercise session
Comparison of nadir glucose from CGM between the exercise strategies.
90 min after the standard meal until 1200 noon the day after each exercise session
CGM Metrics During Late Recovery - Peak Glucose
Time Frame: 90 min after the standard meal until 1200 noon the day after each exercise session
Comparison of peak glucose from CGM between the exercise strategies.
90 min after the standard meal until 1200 noon the day after each exercise session
CGM Metrics During Late Recovery - Mean Glucose
Time Frame: 90 min after the standard meal until 1200 noon the day after each exercise session
Comparison of mean glucose from CGM between the exercise strategies.
90 min after the standard meal until 1200 noon the day after each exercise session
CGM Metrics During Late Recovery - Coefficient of Variation
Time Frame: 90 min after the standard meal until 1200 noon the day after each exercise session
Comparison of the coefficient of variation from CGM between the exercise strategies.
90 min after the standard meal until 1200 noon the day after each exercise session
CGM Metrics During Late Recovery - Time < 54 mg/dL
Time Frame: 90 min after the standard meal until 1200 noon the day after each exercise session
Comparison of percentage of time < 54 mg/dL from CGM between the exercise strategies.
90 min after the standard meal until 1200 noon the day after each exercise session
CGM Metrics During Late Recovery - Time < 70 mg/dL
Time Frame: 90 min after the standard meal until 1200 noon the day after each exercise session
Comparison of percentage of time < 70 mg/dL from CGM between the exercise strategies.
90 min after the standard meal until 1200 noon the day after each exercise session
CGM Metrics During Late Recovery - Time in Range (70-180 mg/dL)
Time Frame: 90 min after the standard meal until 1200 noon the day after each exercise session
Comparison of percentage of time in range (70-180 mg/dL) from CGM between the exercise strategies.
90 min after the standard meal until 1200 noon the day after each exercise session
CGM Metrics During Late Recovery - Time > 180 mg/dL
Time Frame: 90 min after the standard meal until 1200 noon the day after each exercise session
Comparison of percentage of time > 180 mg/dL from CGM between the exercise strategies.
90 min after the standard meal until 1200 noon the day after each exercise session
CGM Metrics During Late Recovery - Time > 250 mg/dL
Time Frame: 90 min after the standard meal until 1200 noon the day after each exercise session
Comparison of percentage of time > 250 mg/dL from CGM between the exercise strategies.
90 min after the standard meal until 1200 noon the day after each exercise session

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Study Chair: Michael Riddell, PhD, York University
  • Study Chair: Michael Rickels, M.D., M.S., University of Pennsylvania
  • Study Chair: Howard Wolpert, M.D., Joslin Diabetes Center
  • Principal Investigator: Stephanie DuBose, M.P.H, Jaeb Center for Health Research

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2016

Primary Completion (Actual)

February 15, 2017

Study Completion (Actual)

February 15, 2017

Study Registration Dates

First Submitted

January 6, 2016

First Submitted That Met QC Criteria

January 18, 2016

First Posted (Estimate)

January 21, 2016

Study Record Updates

Last Update Posted (Actual)

March 3, 2020

Last Update Submitted That Met QC Criteria

February 28, 2020

Last Verified

February 1, 2020

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Diabetes Mellitus, Type 1

Clinical Trials on Basal Insulin Reduction

3
Subscribe