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

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ClinicalTrials.gov Identifier: NCT02660242
Recruitment Status : Completed
First Posted : January 21, 2016
Results First Posted : August 7, 2018
Last Update Posted : August 7, 2018
Sponsor:
Collaborator:
Xeris Pharmaceuticals
Information provided by (Responsible Party):
Jaeb Center for Health Research

Brief Summary:
This project focuses on development of new strategy for the prevention of exercise-associated hypoglycemia using mini-dose glucagon.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 1 Drug: G-Pen Mini™ (glucagon injection) Other: Glucose Tabs Other: Basal Insulin Reduction Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Primary Purpose: Prevention
Official Title: The Use of Mini-dose Glucagon to Prevent Exercise-induced Hypoglycemia in Type 1 Diabetes
Study Start Date : January 2016
Actual Primary Completion Date : February 15, 2017
Actual Study Completion Date : February 15, 2017

Resource links provided by the National Library of Medicine


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.
Other: Basal Insulin Reduction
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).
Other: Glucose Tabs
Dextrose tabs orally (20 grams) 5 minutes before the start of exercise and at 30 minutes of exercise (total 40 grams).
Other Name: over-the-counter oral glucose tablets

Experimental: G-Pen Mini™ (glucagon injection)
Glucagon (150 µg) five minutes before the start of exercise (SQ-abdomen).
Drug: G-Pen Mini™ (glucagon injection)
Glucagon (150 µg) 5 minutes before the start of exercise (SQ-abdomen).
Other Name: mini-dose glucagon




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.



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Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02660242


Locations
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United States, Massachusetts
Joslin Diabetes Center
Boston, Massachusetts, United States, 02215
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Jaeb Center for Health Research
Xeris Pharmaceuticals
Investigators
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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
  Study Documents (Full-Text)

Documents provided by Jaeb Center for Health Research:
Study Protocol  [PDF] April 14, 2016
Statistical Analysis Plan  [PDF] February 24, 2017


Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Jaeb Center for Health Research
ClinicalTrials.gov Identifier: NCT02660242     History of Changes
Other Study ID Numbers: T1DX Mini-dose Exercise
First Posted: January 21, 2016    Key Record Dates
Results First Posted: August 7, 2018
Last Update Posted: August 7, 2018
Last Verified: July 2018

Keywords provided by Jaeb Center for Health Research:
T1D
Type 1 Diabetes
Mini-dose Glucagon
Adults
Exercise
Hypoglycemia

Additional relevant MeSH terms:
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Diabetes Mellitus, Type 1
Hypoglycemia
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin
Insulin, Globin Zinc
Glucagon
Glucagon-Like Peptide 1
Hypoglycemic Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Incretins