Mini-Dose Glucagon to Treat Non-Severe Hypoglycemia

Diabetes Mellitus, Type 1 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02411578
• Other study ID #: T1DX Mini-dose Non-Severe
• Status: Completed
• Phase: Phase 2
• Start date: September 2015
• Est. completion date: May 2016

Study information

• Verified date: February 2020
• Source: Jaeb Center for Health Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: May 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1
• Hypoglycemia

Intervention

Drug:
• G-Pen Mini™ (glucagon injection)
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)

Other:
• Glucose Tablets
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)

Locations

Country	Name	City	State
United States	University of Colorado/Barbara Davis Center for Diabetes	Aurora	Colorado
United States	Joslin Diabetes Center	Boston	Massachusetts
United States	Yale University of Medicine	New Haven	Connecticut
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	SUNY Upstate Medical University	Syracuse	New York

Sponsors (2)

Lead Sponsor	Collaborator
Jaeb Center for Health Research	Xeris Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (7)

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. Review. — View Citation

Cryer PE. The barrier of hypoglycemia in diabetes. Diabetes. 2008 Dec;57(12):3169-76. doi: 10.2337/db08-1084. Review. — View 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. — View Citation

Hasan KS, Kabbani M. Mini-dose glucagon is effective at diabetes camp. J Pediatr. 2004 Jun;144(6):834. — View 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. — View 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. — View 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. Epub 2006 Feb 21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Hypoglycemic Events =50 mg/dl 15 Minutes AND = 70 mg/dl 30 Minutes After Initial Treatment		30 minutes
Secondary	Continuous Glucose Monitor (CGM) Minimum Glucose, Event Level	Minimum glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first hour after start of hypoglycemic event	60 Minutes
Secondary	CGM Maximum Glucose, Event Level	Maximum glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first hour after start of hypoglycemic event	60 Minutes
Secondary	CGM Mean Glucose, Event Level	Median (IQR) reported for mean glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first hour after start of hypoglycemic event	60 Minutes
Secondary	CGM Time in Range, Event Level	Percentage of time 70-180 mg/dL from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first hour after start of hypoglycemic event	60 Minutes
Secondary	CGM Time Below 70 mg/dL, Event Level	Percentage of time <70 mg/dL from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first hour after start of hypoglycemic event	60 Minutes
Secondary	CGM Minimum Glucose, Event Level	Minimum glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first 2 hours after start of hypoglycemic event	120 Minutes
Secondary	CGM Maximum Glucose, Event Level	Maximum glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first 2 hours after start of hypoglycemic event	120 Minutes
Secondary	CGM Mean Glucose, Event Level	Median (IQR) reported for mean glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first 2 hours after start of hypoglycemic event	120 Minutes
Secondary	CGM Time in Range, Event Level	Percentage of time 70-180 mg/dL from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first 2 hours after start of hypoglycemic event	120 Minutes
Secondary	CGM Time Below 70 mg/dL	Percentage of time <70 mg/dL from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first 2 hours after start of hypoglycemic event	120 Minutes
Secondary	CGM Mean Glucose	Median (IQR) reported for mean glucose from CGM data computed over entire 3 weeks of treatment period	3 weeks
Secondary	CGM Time in Range	Percentage of time 70-180 mg/dL from CGM data computed over entire 3 weeks of treatment period	3 weeks
Secondary	CGM Time Below 70	Percentage of time <70 mg/dL from CGM data computed over entire 3 weeks of treatment period	3 weeks
Secondary	CGM Coefficient of Variation	Coefficient of Variation from CGM data computed over entire 3 weeks of treatment period	3 weeks

External Links

•   Safety and Efficacy Study of Mini-Dose Glucagon (G-Pen Mini) in Patients With Type 1 Diabetes