Mini-Dose Glucagon to Treat Non-Severe Hypoglycemia
Condition: Diabetes Mellitus, Type 1
MeSH terms: Hypoglycemia; Diabetes Mellitus, Type 1
Intervention: G-Pen Mini™ (glucagon injection); Glucose Tablets
Intervention description: 1st BG check, 1st treatment
BG is 50-69 mg/dl, treatment is 150 µg of glucagon
BG is 40-49 mg/dl, treatment is 300 µg of glucagon
15 min later, 2nd BG check, 2nd treatment
BG is 60-69 mg/dl, no treatment
BG is 50-59 mg/dl, treatment is 150 µg of glucagon
BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon
30 minutes later, 3rd BG check, 3rd treatment
BG is >=70, no treatment
BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon
(150 µg of glucagon per syringe); 1st BG check, 1st treatment
BG is 50-69 mg/dl, treatment is 15 grams of carbohydrates
BG is 40-49 mg/dl, treatment is 30 grams of carbohydrates
15 min later, 2nd BG check, 2nd treatment
BG is 60-69 mg/dl, no treatment
BG is 50-59 mg/dl, treatment is 15 grams of carbohydrates
BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon
30 minutes later, 3rd BG check, 3rd treatment
BG is >=70, no treatment
BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon
(5 grams of fast-acting carbohydrates (D-Glucose) per tablet)
Intervention MeSH terms: Glucagon; Glucagon-Like Peptide 1
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Maximum age: 64 Years
Healthy volunteers: No
Keywords: T1D; Type 1 diabetes; Mini-dose glucagon; adults; non-severe hypoglycemia

Summary:

      The purpose of this study is to determine if a small dose of glucagon (mini-dose glucagon) is
      effective for the treatment of non-severe hypoglycemia in adults with type 1 diabetes (T1D).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Clinical diagnosis of presumed autoimmune T1D and receiving daily insulin

          2. Age: 18.0 to < 65.0 years

          3. Duration of T1D: ≥2.0 years

          4. Body mass index 20.0 to <35.0 kg/m2 and weight 110 to <250 lbs

          5. HbA1c <8.5% (point of care or local lab, within past month)

          6. Using continuous subcutaneous insulin infusion (CSII) therapy (i.e., insulin pump) for
             at least 3 months, with no plans to discontinue use during the study (and no use of
             active low glucose suspend feature within the last 4 weeks)

          7. Using continuous glucose monitor ≥6 days/week in the last 4 weeks, with no plans to
             discontinue continuous glucose monitor use during the study

          8. Continuous glucose monitor glucose level <70 mg/dl during daytime hours (e.g., 8am -
             10pm) on at least 7 of the past 28 days (a modification can be made for participants
             with non-traditional waking hours) evaluated from downloaded CGM data

          9. Females must meet one of the following criteria:

               -  Of childbearing potential and not currently pregnant (negative pregnancy test) or
                  lactating, and agrees to use an accepted contraceptive regimen as described in
                  the study procedure manual throughout the entire duration of the study (from
                  screening visit until study completion); 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)

         10. 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

         11. Willing to adhere to the protocol requirements for the duration of the study

         12. Participant has a smart phone available and is able to use it daily

         13. Must be enrolled in the T1D Exchange clinic registry or willing to join the clinic
             registry

        Exclusion Criteria:

          1. More than 1 severe hypoglycemic episode in the past 12 months (as defined by an
             episode that required third party assistance for treatment)

          2. More than 1 episode of diabetic ketoacidosis in the past 12 months (as defined by an
             episode diagnosed as diabetic ketoacidosis that required treatment in an emergency
             department or hospitalization)

          3. Presence of cardiovascular, gastrointestinal, liver or kidney disease, or any medical
             condition which, in the judgment of the investigator, could potentiate or predispose
             to undesired effects or could interfere with the absorption, distribution, metabolism,
             or excretion of glucagon or ability to respond appropriately to mild to moderate
             hypoglycemia.

          4. Known presence of hereditary problems of glycogen storage disease, galactose and/or
             lactose intolerance

          5. Males with alcohol use in excess of 3 or more drinks per day, on average and females
             with alcohol use in excess of 2 or more drinks per day, on average

          6. Use of non-insulin anti-diabetic medications

          7. Use of daily systemic beta-blocker

          8. Use of beta-adrenergic agonists, theophylline (or other methylxanthines)

          9. Use of 1st generation anticholinergic drugs (such as Brompheniramine,
             Chlorpheniramine, Dimenhydrinate, Diphenhydramine, and Doxylamine)

         10. Use of systemic corticosteroids

         11. History of hypersensitivity to glucagon or any related product or excipient or severe
             hypersensitivity reactions (such as angioedema) to any drugs

         12. History of epilepsy or seizure disorder

         13. Uncontrolled hypertension, >160 mmHg systolic or >100 mmHg diastolic

         14. Currently a high endurance exerciser or plans to perform high endurance exercise
             during study (from screening visit until study completion)

               -  High endurance exerciser defined as a person who regularly competes in running,
                  cycling, rowing, swimming or any other endurance-based activity for the purpose
                  of competition (>2100 metabolic equivalent of task (MET) minutes per week [i.e. 7
                  METs x 60 minutes x 5 days a week, where 7 METs is equivalent to jogging])

         15. Currently following a very low calorie or other weight-loss diet

         16. 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