Mini-Dose Glucagon to Treat Non-Severe Hypoglycemia

NCT02411578 | Completed Phase 2 Results

• 1 other identifier: T1DX Mini-dose Non-Severe
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 5

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).

Conditions

Diabetes Mellitus, Type 1

Keywords

T1D; Type 1 diabetes; Mini-dose glucagon; adults; non-severe hypoglycemia

Outcome Measures

Primary Outcomes (1)

• Number of Hypoglycemic Events ≥50 mg/dl 15 Minutes AND ≥ 70 mg/dl 30 Minutes After Initial Treatment

  30 minutes

Secondary Outcomes (14)

• Continuous Glucose Monitor (CGM) Minimum Glucose, Event Level

  60 Minutes

• CGM Maximum Glucose, Event Level

  60 Minutes

• CGM Mean Glucose, Event Level

  60 Minutes

• CGM Time in Range, Event Level

  60 Minutes

• CGM Time Below 70 mg/dL, Event Level

  60 Minutes

Study Arms (2)

G-Pen Mini™ (glucagon injection)

EXPERIMENTAL

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.

Drug: G-Pen Mini™ (glucagon injection)

Glucose Tabs

ACTIVE COMPARATOR

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.

Other: Glucose Tablets

Interventions

G-Pen Mini™ (glucagon injection) 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)

Also known as: mini-dose glucagon

G-Pen Mini™ (glucagon injection)

Glucose Tablets 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)

Also known as: over-the-counter oral glucose tablets; glucose tabs

Glucose Tabs

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Clinical diagnosis of presumed autoimmune T1D and receiving daily insulin
• Age: 18.0 to \< 65.0 years
• Duration of T1D: ≥2.0 years
• Body mass index 20.0 to \<35.0 kg/m2 and weight 110 to \<250 lbs
• HbA1c \<8.5% (point of care or local lab, within past month)
• 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)
• Using continuous glucose monitor ≥6 days/week in the last 4 weeks, with no plans to discontinue continuous glucose monitor use during the study
• 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
• 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)
• 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
• Willing to adhere to the protocol requirements for the duration of the study
• Participant has a smart phone available and is able to use it daily
• Must be enrolled in the T1D Exchange clinic registry or willing to join the clinic registry

You may not qualify if:

• More than 1 severe hypoglycemic episode in the past 12 months (as defined by an episode that required third party assistance for treatment)
• 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)
• 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.
• Known presence of hereditary problems of glycogen storage disease, galactose and/or lactose intolerance
• 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
• Use of non-insulin anti-diabetic medications
• Use of daily systemic beta-blocker
• Use of beta-adrenergic agonists, theophylline (or other methylxanthines)
• Use of 1st generation anticholinergic drugs (such as Brompheniramine, Chlorpheniramine, Dimenhydrinate, Diphenhydramine, and Doxylamine)
• Use of systemic corticosteroids
• History of hypersensitivity to glucagon or any related product or excipient or severe hypersensitivity reactions (such as angioedema) to any drugs
• History of epilepsy or seizure disorder
• Uncontrolled hypertension, \>160 mmHg systolic or \>100 mmHg diastolic
• 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 \[i.e. 7 METs x 60 minutes x 5 days a week, where 7 METs is equivalent to jogging\])

Sponsors & Collaborators

• Jaeb Center for Health Research: lead
• Xeris Pharmaceuticals: collaborator

Study Sites (5)

University of Colorado/Barbara Davis Center for Diabetes

Aurora, Colorado, 80045, United States

Location

Yale University of Medicine

New Haven, Connecticut, 06510, United States

Location

Joslin Diabetes Center

Boston, Massachusetts, 02215, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (8)

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

  PMID: 19033403 BACKGROUND

• 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.

  PMID: 20723825 BACKGROUND

• 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.

  PMID: 16492699 BACKGROUND

• 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.

  PMID: 19429875 BACKGROUND

• 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.

  PMID: 11315823 BACKGROUND

• 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.

  PMID: 16509909 BACKGROUND

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

  PMID: 15212060 BACKGROUND

• 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.

  PMID: 28591776 DERIVED

Related Links

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

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Glucagon; Glucose

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Proglucagon; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Hexoses; Monosaccharides; Sugars; Carbohydrates

Results Point of Contact

• Title: Stephanie DuBose
• Organization: Jaeb Center for Health Research

t1dstats2@jaeb.org

813-975-8690

Study Officials

• Morey W Haymond, MD

  Baylor College of Medicine

  STUDY CHAIR

• Stephanie N DuBose, MPH

  Jaeb Center for Health Research

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2015
• First Posted: April 8, 2015
• Study Start: September 1, 2015
• Primary Completion: April 1, 2016
• Study Completion: May 1, 2016
• Last Updated: March 3, 2020
• Results First Posted: October 23, 2017

Record last verified: 2020-02

Locations

US (5)