Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Mini-Dose Glucagon to Treat Non-Severe Hypoglycemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02411578
Recruitment Status : Completed
First Posted : April 8, 2015
Results First Posted : October 23, 2017
Last Update Posted : March 3, 2020
Sponsor:
Collaborator:
Xeris Pharmaceuticals
Information provided by (Responsible Party):
Jaeb Center for Health Research

Tracking Information
First Submitted Date  ICMJE March 27, 2015
First Posted Date  ICMJE April 8, 2015
Results First Submitted Date  ICMJE August 3, 2017
Results First Posted Date  ICMJE October 23, 2017
Last Update Posted Date March 3, 2020
Study Start Date  ICMJE September 2015
Actual Primary Completion Date April 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 20, 2017)
Number of Hypoglycemic Events ≥50 mg/dl 15 Minutes AND ≥ 70 mg/dl 30 Minutes After Initial Treatment [ Time Frame: 30 minutes ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 3, 2015)
Proportion of events ≥50 mg/dl 15 minutes AND ≥ 70 mg/dl 30 minutes after the start of each non-severe hypoglycemic event (with starting blood glucose 50-69 mg/dl) [ Time Frame: the two 3 week periods (6 weeks total) of the Randomized Clinical Trial (RCT) Crossover Trial Phase ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 20, 2017)
  • Continuous Glucose Monitor (CGM) Minimum Glucose, Event Level [ Time Frame: 60 Minutes ]
    Minimum glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first hour after start of hypoglycemic event
  • CGM Maximum Glucose, Event Level [ Time Frame: 60 Minutes ]
    Maximum glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first hour after start of hypoglycemic event
  • CGM Mean Glucose, Event Level [ Time Frame: 60 Minutes ]
    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
  • CGM Time in Range, Event Level [ Time Frame: 60 Minutes ]
    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
  • CGM Time Below 70 mg/dL, Event Level [ Time Frame: 60 Minutes ]
    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
  • CGM Minimum Glucose, Event Level [ Time Frame: 120 Minutes ]
    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
  • CGM Maximum Glucose, Event Level [ Time Frame: 120 Minutes ]
    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
  • CGM Mean Glucose, Event Level [ Time Frame: 120 Minutes ]
    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
  • CGM Time in Range, Event Level [ Time Frame: 120 Minutes ]
    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
  • CGM Time Below 70 mg/dL [ Time Frame: 120 Minutes ]
    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
  • CGM Mean Glucose [ Time Frame: 3 weeks ]
    Median (IQR) reported for mean glucose from CGM data computed over entire 3 weeks of treatment period
  • CGM Time in Range [ Time Frame: 3 weeks ]
    Percentage of time 70-180 mg/dL from CGM data computed over entire 3 weeks of treatment period
  • CGM Time Below 70 [ Time Frame: 3 weeks ]
    Percentage of time <70 mg/dL from CGM data computed over entire 3 weeks of treatment period
  • CGM Coefficient of Variation [ Time Frame: 3 weeks ]
    Coefficient of Variation from CGM data computed over entire 3 weeks of treatment period
Original Secondary Outcome Measures  ICMJE
 (submitted: April 3, 2015)
  • Proportion of events ≥50 mg/dl 15 minutes AND ≥ 70 mg/dl 30 minutes after the start of each non-severe hypoglycemic event (with starting blood glucose 40-49 mg/dl) [ Time Frame: the two 3 week periods (6 weeks total) of the Randomized Clinical Trial (RCT) Crossover Trial Phase ]
  • Overall continuous glucose monitor (CGM) metric: Mean glucose [ Time Frame: the two 3 week periods (6 weeks) of the Randomized Clinical Trial (RCT) Crossover Trial Phase ]
    CGM data will be used to compute mean glucose by treatment period for participants who complete both periods
  • Overall continuous glucose monitor (CGM) metric: Time in range of 70 to 180 mg/dl [ Time Frame: the two 3 week periods (6 weeks) of the Randomized Clinical Trial (RCT) Crossover Trial Phase ]
    CGM data will be used to compute the time participants were in range of 70 to 180 mg/dl by treatment period for participants who complete both periods
  • Overall continuous glucose monitor (CGM) metric: Glucose variability (coefficient of variation) [ Time Frame: the two 3 week periods (6 weeks) of the Randomized Clinical Trial (RCT) Crossover Trial Phase ]
    CGM data will be used to compute glucose variability by treatment period for participants who complete both periods
  • CGM Metric: Maximum glucose level [ Time Frame: 0-11 weeks (duration of study) ]
    Maximum glucose level will be computed for treated hypoglycemic events in which blood glucoses at time 0 was 40-49 or 50-69 md/dl, in a time period following treatment (1 hour or until receipt of next insulin dose or meal)
  • CGM Metric: Minimum glucose level [ Time Frame: 0-11 weeks (duration of study) ]
    Minimum glucose level will be computed for treated hypoglycemic events in which blood glucoses at time 0 was 40-49 or 50-69 md/dl, in a time period following treatment (1 hour or until receipt of next insulin dose or meal)
  • CGM Metric:Mean Glucose level [ Time Frame: 0-11 weeks (duration of study) ]
    Mean glucose level will be computed for treated hypoglycemic events in which blood glucoses at time 0 was 40-49 or 50-69 md/dl, in a time period following treatment (1 hour or until receipt of next insulin dose or meal)
  • CGM Metric: Time in range of 70 to 180 mg/dl [ Time Frame: 0-11 weeks (duration of study) ]
    Time in range of 70 to 180 mg/dl will be computed for treated hypoglycemic events in which blood glucoses at time 0 was 40-49 or 50-69 md/dl, in a time period following treatment (1 hour or until receipt of next insulin dose or meal)
  • CGM Metric:Time to increase of glucose level to 100 mg/dl or by 30 mg/dl [ Time Frame: 0-11 weeks (duration of study) ]
    Time to increase of glucose level to 100 mg/dl or by 30 mg/dl will be computed for treated hypoglycemic events in which blood glucoses at time 0 was 40-49 or 50-69 md/dl, in a time period following treatment (1 hour or until receipt of next insulin dose or meal)
  • CGM Metric: Frequency of CGM glucose levels below 70 after treatment of initial event [ Time Frame: 0-11 weeks (duration of study) ]
    Frequency of CGM glucose levels below 70 after treatment of initial event will be computed for treated hypoglycemic events in which blood glucoses at time 0 was 40-49 or 50-69 md/dl, in a time period following treatment (1 hour or until receipt of next insulin dose or meal)
  • Symptoms associated with non-severe hypoglycemic events [ Time Frame: 0-11 weeks (duration of study) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: April 3, 2015)
  • Number of severe hypoglycemia events as defined in the description. [ Time Frame: 0-11 weeks (duration of study) ]
    Definition: an event required assistance of another person due to altered consciousness, and required another person to actively administer carbohydrate, glucagon, or other resuscitative actions. This means that the participant was impaired cognitively to the point that he/she was unable to treat himself/herself, was unable to verbalize his/ her needs, was incoherent, disoriented, and/or combative, or experienced seizure or coma. These episodes may be associated with sufficient neuroglycopenia to induce seizure or coma. If plasma glucose measurements are not available during such an event, neurological recovery attributable to the restoration of plasma glucose to normal is considered sufficient evidence that the event was induced by a low plasma glucose concentration. Severe hypoglycemia events will be tabulated by treatment group.
  • Number of hyperglycemia (DKA) events as defined in the description [ Time Frame: 0-11 weeks (duration of study) ]
    Definition: the Diabetes Control and Complications Trial (DCCT) and described below, or in the absence of DKA if evaluation or treatment was obtained from a health care provider or an acute event involving hyperglycemia or ketosis. Hyperglycemic events are classified as DKA if all of the following are present:
    • Symptoms such as polyuria, polydipsia, nausea, or vomiting
    • Serum ketones >1.5 mmol/L or large/moderate urine ketones
    • Either arterial blood pH <7.30 or venous pH <7.24 or serum bicarbonate <15
    • Treatment provided in a health care facility
    Hyperglycemia events will be tabulated by treatment group.
 
Descriptive Information
Brief Title  ICMJE Mini-Dose Glucagon to Treat Non-Severe Hypoglycemia
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Diabetes Mellitus, Type 1
Intervention  ICMJE
  • Drug: 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)

    Other Name: mini-dose glucagon
  • Other: 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)

    Other Name: over-the-counter oral glucose tablets; glucose tabs
Study Arms  ICMJE
  • Experimental: 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.

    Intervention: Drug: G-Pen Mini™ (glucagon injection)
  • Active Comparator: 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.

    Intervention: Other: Glucose Tablets
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 24, 2016)
26
Original Estimated Enrollment  ICMJE
 (submitted: April 3, 2015)
48
Actual Study Completion Date  ICMJE May 2016
Actual Primary Completion Date April 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 64 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02411578
Other Study ID Numbers  ICMJE T1DX Mini-dose Non-Severe
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jaeb Center for Health Research
Study Sponsor  ICMJE Jaeb Center for Health Research
Collaborators  ICMJE Xeris Pharmaceuticals
Investigators  ICMJE
Study Chair: Morey W Haymond, MD Baylor College of Medicine
Principal Investigator: Stephanie N DuBose, MPH Jaeb Center for Health Research
PRS Account Jaeb Center for Health Research
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP