Clinical trial NCT02660242: The Use of Mini-dose Glucagon to Prevent Exercise-induced Hypoglycemia in Type 1 Diabetes
Official title: The Use of Mini-dose Glucagon to Prevent Exercise-induced Hypoglycemia in Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 1
Keywords: T1D
Type 1 Diabetes
Mini-dose Glucagon
Adults
Exercise
Hypoglycemia
Lead sponsor: Jaeb Center for Health Research
Sponsor class: OTHER
Collaborators: name: Xeris Pharmaceuticals
First posted: 2016-01-21
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

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

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.

Eligibility 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

Primary outcomes:
measure: Glycemic Response During Exercise and Early Recovery
timeFrame: 0 to 75 minutes following exercise initiation (0, 5, 10, 15, 25, 35, 45, 50, 55, 60, 75 min)
Secondary outcomes:
measure: Number of Participants With Hypoglycemia (<70 mg/dL) During Exercise and Early Recovery
timeFrame: 0 to 75 minutes following exercise initiation
measure: Number of Participants With Hyperglycemia (≥250 mg/dL) During Exercise and Early Recovery
timeFrame: 0 to 75 minutes following exercise initiation
measure: Continuous Glucose Monitor (CGM) Metrics During Late Recovery - Nadir Glucose
timeFrame: 90 min after the standard meal until 1200 noon the day after each exercise session
measure: CGM Metrics During Late Recovery - Peak Glucose
timeFrame: 90 min after the standard meal until 1200 noon the day after each exercise session
measure: CGM Metrics During Late Recovery - Mean Glucose
timeFrame: 90 min after the standard meal until 1200 noon the day after each exercise session
measure: CGM Metrics During Late Recovery - Coefficient of Variation
timeFrame: 90 min after the standard meal until 1200 noon the day after each exercise session
measure: CGM Metrics During Late Recovery - Time < 54 mg/dL
timeFrame: 90 min after the standard meal until 1200 noon the day after each exercise session
measure: CGM Metrics During Late Recovery - Time < 70 mg/dL
timeFrame: 90 min after the standard meal until 1200 noon the day after each exercise session
measure: CGM Metrics During Late Recovery - Time in Range (70-180 mg/dL)
timeFrame: 90 min after the standard meal until 1200 noon the day after each exercise session
measure: CGM Metrics During Late Recovery - Time > 180 mg/dL
timeFrame: 90 min after the standard meal until 1200 noon the day after each exercise session
measure: CGM Metrics During Late Recovery - Time > 250 mg/dL
timeFrame: 90 min after the standard meal until 1200 noon the day after each exercise session
Other outcomes:
Locations:
city: Boston
country: United States
facility: Joslin Diabetes Center
state: Massachusetts
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: York University
name: Michael Riddell, PhD
role: STUDY_CHAIR
affiliation: University of Pennsylvania
name: Michael Rickels, M.D., M.S.
role: STUDY_CHAIR
affiliation: Joslin Diabetes Center
name: Howard Wolpert, M.D.
role: STUDY_CHAIR
affiliation: Jaeb Center for Health Research
name: Stephanie DuBose, M.P.H
role: PRINCIPAL_INVESTIGATOR
References:
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