Mini-Dose Glucagon to Treat Non-Severe Hypoglycemia

NCT ID: NCT02411578

Last Updated: 2020-03-03

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

26 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-09-30

Study Completion Date

2016-05-31

Brief Summary

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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

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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.

Conditions

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Diabetes Mellitus, Type 1

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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G-Pen Mini™ (glucagon injection)

Participants are to check blood glucose (BG) with study meter once their continuous glucose monitor (CGM) reads \<70 mg/dl or they experience symptoms. Participants will be instructed to treat using mini-dose glucagon for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event).

For every event, participant will check BG with meter 3 times and treat according to protocol instructions based on BG measurement.

Group Type EXPERIMENTAL

G-Pen Mini™ (glucagon injection)

Intervention Type DRUG

1st BG check, 1st treatment

1. BG is 50-69 mg/dl, treatment is 150 µg of glucagon
2. BG is 40-49 mg/dl, treatment is 300 µg of glucagon

15 min later, 2nd BG check, 2nd treatment

1. BG is 60-69 mg/dl, no treatment
2. BG is 50-59 mg/dl, treatment is 150 µg of glucagon
3. 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

1. BG is \>=70, no treatment
2. BG is \<70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon

(150 µg of glucagon per syringe)

Glucose Tabs

Participants are to check their blood glucose (BG) with study meter once their continuous glucose meter reads \<70 mg/dl or they experience symptoms. Participants will be instructed to treat using oral glucose tablets for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event).

For every event, participant will check BG with meter 3 times and treat according to protocol instructions based on BG measurement.

Group Type ACTIVE_COMPARATOR

Glucose Tablets

Intervention Type OTHER

1st BG check, 1st treatment

1. BG is 50-69 mg/dl, treatment is 15 grams of carbohydrates
2. BG is 40-49 mg/dl, treatment is 30 grams of carbohydrates

15 min later, 2nd BG check, 2nd treatment

1. BG is 60-69 mg/dl, no treatment
2. BG is 50-59 mg/dl, treatment is 15 grams of carbohydrates
3. 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

1. BG is \>=70, no treatment
2. 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)

Interventions

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G-Pen Mini™ (glucagon injection)

1st BG check, 1st treatment

1. BG is 50-69 mg/dl, treatment is 150 µg of glucagon
2. BG is 40-49 mg/dl, treatment is 300 µg of glucagon

15 min later, 2nd BG check, 2nd treatment

1. BG is 60-69 mg/dl, no treatment
2. BG is 50-59 mg/dl, treatment is 150 µg of glucagon
3. 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

1. BG is \>=70, no treatment
2. BG is \<70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon

(150 µg of glucagon per syringe)

Intervention Type DRUG

Glucose Tablets

1st BG check, 1st treatment

1. BG is 50-69 mg/dl, treatment is 15 grams of carbohydrates
2. BG is 40-49 mg/dl, treatment is 30 grams of carbohydrates

15 min later, 2nd BG check, 2nd treatment

1. BG is 60-69 mg/dl, no treatment
2. BG is 50-59 mg/dl, treatment is 15 grams of carbohydrates
3. 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

1. BG is \>=70, no treatment
2. 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 Type OTHER

Other Intervention Names

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mini-dose glucagon over-the-counter oral glucose tablets; glucose tabs

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

64 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Xeris Pharmaceuticals

INDUSTRY

Sponsor Role collaborator

Jaeb Center for Health Research

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Morey W Haymond, MD

Role: STUDY_CHAIR

Baylor College of Medicine

Stephanie N DuBose, MPH

Role: PRINCIPAL_INVESTIGATOR

Jaeb Center for Health Research

Locations

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University of Colorado/Barbara Davis Center for Diabetes

Aurora, Colorado, United States

Site Status

Yale University of Medicine

New Haven, Connecticut, United States

Site Status

Joslin Diabetes Center

Boston, Massachusetts, United States

Site Status

SUNY Upstate Medical University

Syracuse, New York, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

References

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Cryer PE. The barrier of hypoglycemia in diabetes. Diabetes. 2008 Dec;57(12):3169-76. doi: 10.2337/db08-1084. No abstract available.

Reference Type BACKGROUND
PMID: 19033403 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20723825 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16492699 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19429875 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11315823 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16509909 (View on PubMed)

Hasan KS, Kabbani M. Mini-dose glucagon is effective at diabetes camp. J Pediatr. 2004 Jun;144(6):834. No abstract available.

Reference Type BACKGROUND
PMID: 15212060 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28591776 (View on PubMed)

Related Links

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https://clinicaltrials.gov/ct2/show/NCT02081014?term=Xeris+G-Pen&rank=1

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

Other Identifiers

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T1DX Mini-dose Non-Severe

Identifier Type: -

Identifier Source: org_study_id

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