Clinical trial NCT02411578: Mini-Dose Glucagon to Treat Non-Severe Hypoglycemia
Official title: Mini-Dose Glucagon for Adults With Type 1 Diabetes: A Study to Assess the Efficacy and Safety of Mini-dose Glucagon for Treatment of Non-severe Hypoglycemia in Adults With 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
non-severe hypoglycemia
Lead sponsor: Jaeb Center for Health Research
Sponsor class: OTHER
Collaborators: name: Xeris Pharmaceuticals
First posted: 2015-04-08
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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).

Detailed description: There are three phases included in this study: (1) Pre-crossover Trial Run-in Phase, (2) Randomized Clinical Trial (RCT) Crossover Trial Phase, and (3) Post-Crossover Trial Extension Phase.

1. Run-in Phase:

   Prior to commencing the crossover trial, study enrollment will begin with a 2 week run-in phase to assess hypoglycemia eligibility and compliance.
2. Crossover Trial Phase:

   The Crossover Trial Phase will consist of two (3-week) periods.

   The Crossover Trial Phase will include up to 24 participants who complete these study periods. Participants who do not complete both periods or who do not have at least one event during both periods may be replaced.

   During the Crossover Trial Phase participants will be randomized into two groups: (1) Group A will use mini-dose glucagon in period 1 and oral glucose tablets in period 2 and (2) Group B will use oral glucose tablets in period 1 and mini-dose glucagon in period 2. Each group with follow the applicable treatment arm according to their randomized group.
3. Extension Phase:

The Post-Crossover Trial phase will commence upon completion of the second 3-week period of the Crossover Trial Phase. Participants will have a 3 week phase during which time they will decide whether to use mini-dose glucagon or glucose tablets to treat each non-severe hypoglycemic event or to prevent hypoglycemia.

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

Primary outcomes:
measure: Number of Hypoglycemic Events ≥50 mg/dl 15 Minutes AND ≥ 70 mg/dl 30 Minutes After Initial Treatment
timeFrame: 30 minutes
Secondary outcomes:
measure: Continuous Glucose Monitor (CGM) Minimum Glucose, Event Level
timeFrame: 60 Minutes
measure: CGM Maximum Glucose, Event Level
timeFrame: 60 Minutes
measure: CGM Mean Glucose, Event Level
timeFrame: 60 Minutes
measure: CGM Time in Range, Event Level
timeFrame: 60 Minutes
measure: CGM Time Below 70 mg/dL, Event Level
timeFrame: 60 Minutes
measure: CGM Minimum Glucose, Event Level
timeFrame: 120 Minutes
measure: CGM Maximum Glucose, Event Level
timeFrame: 120 Minutes
measure: CGM Mean Glucose, Event Level
timeFrame: 120 Minutes
measure: CGM Time in Range, Event Level
timeFrame: 120 Minutes
measure: CGM Time Below 70 mg/dL
timeFrame: 120 Minutes
measure: CGM Mean Glucose
timeFrame: 3 weeks
measure: CGM Time in Range
timeFrame: 3 weeks
measure: CGM Time Below 70
timeFrame: 3 weeks
measure: CGM Coefficient of Variation
timeFrame: 3 weeks
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado/Barbara Davis Center for Diabetes
state: Colorado
city: New Haven
country: United States
facility: Yale University of Medicine
state: Connecticut
city: Boston
country: United States
facility: Joslin Diabetes Center
state: Massachusetts
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Baylor College of Medicine
name: Morey W Haymond, MD
role: STUDY_CHAIR
affiliation: Jaeb Center for Health Research
name: Stephanie N DuBose, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cryer PE. The barrier of hypoglycemia in diabetes. Diabetes. 2008 Dec;57(12):3169-76. doi: 10.2337/db08-1084. No abstract available.
citation: Cryer PE. Hypoglycemia in type 1 diabetes mellitus. Endocrinol Metab Clin North Am. 2010 Sep;39(3):641-54. doi: 10.1016/j.ecl.2010.05.003.
citation: Raju B, Arbelaez AM, Breckenridge SM, Cryer PE. Nocturnal hypoglycemia in type 1 diabetes: an assessment of preventive bedtime treatments. J Clin Endocrinol Metab. 2006 Jun;91(6):2087-92. doi: 10.1210/jc.2005-2798. Epub 2006 Feb 21.
citation: Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group; Beck RW, Hirsch IB, Laffel L, Tamborlane WV, Bode BW, Buckingham B, Chase P, Clemons R, Fiallo-Scharer R, Fox LA, Gilliam LK, Huang ES, Kollman C, Kowalski AJ, Lawrence JM, Lee J, Mauras N, O'Grady M, Ruedy KJ, Tansey M, Tsalikian E, Weinzimer SA, Wilson DM, Wolpert H, Wysocki T, Xing D. The effect of continuous glucose monitoring in well-controlled type 1 diabetes. Diabetes Care. 2009 Aug;32(8):1378-83. doi: 10.2337/dc09-0108. Epub 2009 May 8.
citation: Haymond MW, Schreiner B. Mini-dose glucagon rescue for hypoglycemia in children with type 1 diabetes. Diabetes Care. 2001 Apr;24(4):643-5. doi: 10.2337/diacare.24.4.643.
citation: Hartley M, Thomsett MJ, Cotterill AM. Mini-dose glucagon rescue for mild hypoglycaemia in children with type 1 diabetes: the Brisbane experience. J Paediatr Child Health. 2006 Mar;42(3):108-11. doi: 10.1111/j.1440-1754.2006.00807.x.
citation: Hasan KS, Kabbani M. Mini-dose glucagon is effective at diabetes camp. J Pediatr. 2004 Jun;144(6):834. No abstract available.
citation: Haymond MW, DuBose SN, Rickels MR, Wolpert H, Shah VN, Sherr JL, Weinstock RS, Agarwal S, Verdejo AS, Cummins MJ, Newswanger B, Beck RW; T1D Exchange Mini-dose Glucagon Study Group. Efficacy and Safety of Mini-Dose Glucagon for Treatment of Nonsevere Hypoglycemia in Adults With Type 1 Diabetes. J Clin Endocrinol Metab. 2017 Aug 1;102(8):2994-3001. doi: 10.1210/jc.2017-00591.