Back to resultsClosed-Loop Glucagon Pump for Treatment of Post-Bariatric Hypoglycemia
Primary Purpose
Post-bariatric Hypoglycemia
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
glucagon
Closed loop glucagon pump
Sponsored by
About this trial
This is an interventional prevention trial for Post-bariatric Hypoglycemia
Eligibility Criteria
Inclusion Criteria:
- Males or females diagnosed with ongoing post-bariatric hypoglycemia with prior episodes of neuroglycopenia, unresponsive to dietary intervention (low glycemic index, controlled carbohydrate portions) and trial of acarbose therapy at the maximally tolerated dose.
- Age 18-65 years of age, inclusive, at screening.
- Willingness to provide informed consent and follow all study procedures, including attending all scheduled visits.
Exclusion Criteria:
- Documented hypoglycemia occurring in the fasting state (> 12 hours fast);
- Chronic kidney disease stage 4 or 5 (including end-stage renal disease);
- Hepatic disease, including serum alanine transaminase (ALT) or aspartate aminotransferase (AST) greater than or equal to 3 times the upper limit of normal; hepatic synthetic insufficiency as defined as serum albumin < 3.0 g/dL; or serum bilirubin > 2.0;
- Congestive heart failure, New York Heart Association (NYHA )class II, III or IV;
- History of myocardial infarction, unstable angina or revascularization within the past 6 months or 2 or more risk factors for coronary artery disease including diabetes, uncontrolled hypertension, uncontrolled hyperlipidemia, and active tobacco use;
- History of cardiac arrhythmia or arrhythmia detected by EKG during the screening visit;
- History of syncope (unrelated to hypoglycemia) or diagnosed cardiac arrhythmia
- Concurrent administration of β-blocker therapy;
- History of a cerebrovascular accident;
- Seizure disorder (other than with suspect or documented hypoglycemia);
- Active treatment with any diabetes medications except for acarbose;
- Active malignancy, except basal cell or squamous cell skin cancers;
- Personal or family history of pheochromocytoma or disorder with increased risk of pheochromocytoma (MEN 2, neurofibromatosis, or Von Hippel-Lindau disease);
- Known insulinoma or glucagonoma;
- Major surgical operation within 30 days prior to screening;
- Hematocrit < 33%;
- Bleeding disorder, treatment with warfarin, or platelet count <50,000;
- Blood donation (1 pint of whole blood) within the past 2 months;
- Active alcohol abuse or substance abuse;
- Current administration of oral or parenteral corticosteroids;
- Pregnancy and/ or Lactation: For women of childbearing potential: there is a requirement for a negative urine pregnancy test and for agreement to use contraception during the study and for at least 1 month after participating in the study. Acceptable contraception includes birth control pill / patch / vaginal ring, Depo-Provera, Norplant, an intrauterine device (IUD), the double barrier method (the woman uses a diaphragm and spermicide and the man uses a condom), or abstinence;
- Use of an investigational drug within 30 days prior to screening;
- Current use of anticholinergic medications;
- Allergy to a component of the study drug.
Sites / Locations
- Joslin Diabetes Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Other
Other
Arm Label
Study drug (glucagon) first, placebo second
Placebo first, study drug (glucagon) second
Arm Description
Each subject will have two mixed meal tolerance tests performed. Each will be randomized to receive either glucagon or matched placebo during the first testing session. A participant could receive 2 doses of the study drug or placebo at each study visit. The opposite treatment will be given during the second testing session after a 1-2 week washout period. Both participants and the study team will be blinded to the intervention being used during each session.
Each subject will have two mixed meal tolerance tests performed. Each will be randomized to receive either glucagon or matched placebo during the first testing session. A participant could receive 2 doses of the study drug or placebo at each study visit. The opposite treatment will be given during the second testing session after a 1-2 week washout period. Both participants and the study team will be blinded to the intervention being used during each session.
Outcomes
Primary Outcome Measures
Number of Participants With Meal-provoked Hypoglycemia, Defined as Sensor Glucose <65 mg/dL
A primary endpoint for this study is the prevention of meal provoked hypoglycemia, defined as sensor glucose levels below <65 mg/dl, comparing study drug to control.
Number of Participants With Meal-provoked Hypoglycemia, Defined as Plasma Glucose <65 mg/dL
A primary endpoint for this study is prevention of meal provoked hypoglycemia, defined as plasma glucose levels below <65 mg/dl, comparing study drug to control
Secondary Outcome Measures
Number of Participants With Meal-provoked Hypoglycemia, Defined as Sensor Glucose <60 mg/dL
Prevention of meal / provoked hypoglycemia, defined as sensor glucose levels below <60 mg/dl, comparing vehicle to control
Number of Participants With Rebound Hyperglycemia (Defined as Glucose Levels Above 180 mg/dl).
Compare outcomes for glucagon versus vehicle infusions for prevention of rebound hyperglycemia (defined as glucose levels above 180 mg/dl).
Number of Participants With Hypoglycemia Rescue Administered
Protocol-specified rescue delivery of IV glucose was performed if plasma glucose <55 mg/dL and/or significant neuroglycopenia developed.
Number of Participants With Meal-provoked Hypoglycemia, Defined as Plasma Glucose <60 mg/dL
Prevention of meal / provoked hypoglycemia, defined as plasma glucose levels below <60 mg/dl, comparing vehicle to control
Number of Participants With Meal-provoked Hypoglycemia, Defined as Plasma Glucose <55 mg/dL
Prevention of meal / provoked hypoglycemia, defined as plasma glucose levels below <55 mg/dl, comparing vehicle to control
Number of Participants With Meal-provoked Hypoglycemia, Defined as Sensor Glucose <55 mg/dL
Prevention of meal / provoked hypoglycemia, defined as sensor glucose levels below <55 mg/dl, comparing vehicle to control
Percent Time Plasma Glucose in Range After the Final Dose of Study Drug or Vehicle, Which Was Either 1 or 2 Doses Depending on Patient Response
Compare outcomes for glucagon versus vehicle infusions for percent time plasma glucose in range (180-65mg/dL) after the final dose, which was either 1 or 2 doses depending on patient response
Percent Time Sensor Glucose in Range After Drug Delivery After the Final Dose of Study Drug or Vehicle, Which Was Either 1 or 2 Doses Depending on Patient Response
Compare outcomes for glucagon versus vehicle infusions for percent time sensor glucose in range (180-65mg/dL) after the final dose, which was either 1 or 2 doses depending on patient response
Meal Provoked Nadir Plasma Glucose
Nadir plasma glucose (mg/dl) during meal testing, comparing vehicle to control
Meal Provoked Nadir Sensor Glucose
Nadir sensor glucose (mg/dl) during meal testing, comparing vehicle to control
Time to Nadir Plasma Glucose After Mixed Meal (Min)
Time to Nadir Sensor Glucose After Mixed Meal (Min)
Time to Alarm During Mixed Meal Testing (Minutes)
Time to alarm represents the time for the first alarm to occur during mixed meal testing. Alarms are triggered by hypoglycemia (sensor glucose < 65 mg/dL), or by the algorithm predicting that hypoglycemia will occur in less than 30 minutes (taking into account current sensor glucose level (between 65-150 mg/dL) and the rate of change of a rapidly falling sensor glucose level). In the latter case, the alarm is activated even if glucose levels are within the normoglycemic range to allow early detection and response. During both glucagon and vehicle treatment visits, all participants received either 300 μg of glucagon or the equivalent volume of vehicle with the first alarm.
Time to Delivery (Min)
Time to delivery (min) of study drug during mixed meal testing
Sensor Glucose at Time of Alarm 1 During Mixed Meal Testing (mg/dL)
This is the sensor glucose at which time the first alarm occurred during the mixed meal testing. Alarms are triggered by hypoglycemia (sensor glucose < 65 mg/dL), or by the algorithm predicting that hypoglycemia will occur in less than 30 minutes (taking into account current sensor glucose level (between 65-150 mg/dL) and the rate of change of a rapidly falling sensor glucose level). In the latter case, the alarm is activated even if glucose levels are within the normoglycemic range to allow early detection and response. During both glucagon and vehicle treatment visits, all participants received either 300 μg of glucagon or the equivalent volume of vehicle with the first alarm.
Capillary Glucose at Time of Alarm 1 During Mixed Meal Testing (mg/dL)
This is the capillary glucose at which time the first alarm occurred during the mixed meal testing. Alarms are triggered by hypoglycemia (sensor glucose < 65 mg/dL), or by the algorithm predicting that hypoglycemia will occur in less than 30 minutes (taking into account current sensor glucose level (between 65-150 mg/dL) and the rate of change of a rapidly falling sensor glucose level). In the latter case, the alarm is activated even if glucose levels are within the normoglycemic range to allow early detection and response. During both glucagon and vehicle treatment visits, all participants received either 300 μg of glucagon or the equivalent volume of vehicle with the first alarm.
Sensor Glucose at Time of Alarm 2 During Mixed Meal Testing (mg/dL)
This is the sensor glucose at which time the second alarm occurred during the mixed meal testing. Alarms are triggered by hypoglycemia (sensor glucose < 65 mg/dL), or by the algorithm predicting that hypoglycemia will occur in less than 30 minutes (taking into account current sensor glucose level (between 65-150 mg/dL) and the rate of change of a rapidly falling sensor glucose level). In the latter case, the alarm is activated even if glucose levels are within the normoglycemic range to allow early detection and response. During both glucagon and vehicle treatment visits, all participants received either 300 μg of glucagon or the equivalent volume of vehicle with the first alarm.
Capillary Glucose at Time of Alarm 2 During Mixed Meal Testing (mg/dL)
This is the capillary glucose at which time the second alarm occurred during the mixed meal testing. Alarms are triggered by hypoglycemia (sensor glucose < 65 mg/dL), or by the algorithm predicting that hypoglycemia will occur in less than 30 minutes (taking into account current sensor glucose level (between 65-150 mg/dL) and the rate of change of a rapidly falling sensor glucose level). In the latter case, the alarm is activated even if glucose levels are within the normoglycemic range to allow early detection and response. During both glucagon and vehicle treatment visits, all participants received either 300 μg of glucagon or the equivalent volume of vehicle with the first alarm.
Pain Score at Time of First Dose Delivery of Study Drug, Versus Pain Score at Time of First Dose Delivery of Placebo (Comparing First Delivery Pain Scores for Visit Where Participant Received Study Drug vs. Visit Where Participant Received Placebo).
Pain score was assessed verbally, 1 is the least pain (none), 10 is the most severe pain. Pain score at the time of the first administration was compared for the visit where the participant received the study drug vs. the visit where the participant received the placebo. A participant could receive 2 doses of the study drug or placebo at each visit. All 12 participants completed both the study drug phase and the placebo phase. The pain scores for the first administration of study drug vs. first administration of placebo for these two visits were compared. Whether the participant was assigned to the study drug glucagon (vs. placebo) at the first or second MMTT was determined by randomization.
Pain Score at Time of Second Dose Delivery of Study Drug, Versus Pain Score at Time of Second Dose Delivery of Placebo (Comparing Second Delivery Pain Scores for Visit Where Participant Received Study Drug vs. Visit Where Participant Received Placebo).
Pain score was assessed verbally, 1 is the least pain (none), 10 is the most severe pain. Pain score at the time of the second administration was compared for the visit where the participant received the study drug vs. the visit where the participant received the placebo. A participant could receive 2 doses of the study drug or placebo at each visit. All 12 participants completed both the study drug phase and the placebo phase. The pain scores from the second administration of study drug vs. second administration of placebo for these two visits were compared. Whether the participant was assigned to the study drug glucagon (vs. placebo) at the first or second MMTT was determined by randomization.
Full Information
NCT ID
NCT03255629
First Posted
August 10, 2017
Last Updated
August 7, 2022
Sponsor
Joslin Diabetes Center
Collaborators
National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Xeris Pharmaceuticals, Harvard University
1. Study Identification
Unique Protocol Identification Number
NCT03255629
Brief Title
Closed-Loop Glucagon Pump for Treatment of Post-Bariatric Hypoglycemia
Official Title
Closed-Loop Glucagon Pump for Treatment of Post-Bariatric Hypoglycemia
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
September 19, 2017 (Actual)
Primary Completion Date
August 22, 2018 (Actual)
Study Completion Date
August 22, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Joslin Diabetes Center
Collaborators
National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Xeris Pharmaceuticals, Harvard University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
To assess the efficacy of a closed loop glucagon system to prevent and treat hypoglycemia occurring in patients with Post-Bariatric Hypoglycemia (PBH) in response to meals and exercise.
Detailed Description
A control system for sensor-guided delivery was previously developed and tested in a Proof-of-Concept (POC) study in a clinical research setting during 9 mixed meal tolerance tests in 8 unique patients with severe hypoglycemia following bariatric surgery. This optimized algorithm will now be implemented to deliver stable glucagon in a closed-loop system.
A randomized, placebo-controlled, masked trial will be conducted to assess the efficacy of the closed loop system to prevent and treat hypoglycemia occurring in patients with PBH in response to meals (part 1). Part 2 will test whether the closed loop system can also prevent and treat hypoglycemia in patients with PBH in response to exercise. A manufacturing program from our collaborating team at Xeris Pharmaceuticals will continue to produce supplies of glucagon for the clinical trial in a current good manufacturing practice (cGMP) facility, with continued shelf-life stability testing.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Post-bariatric Hypoglycemia
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1, Phase 2
Interventional Study Model
Crossover Assignment
Model Description
A randomization scheme will be devised to assign half the subjects to receive glucagon during their first challenge visit and the other half to receive vehicle during their first challenge visit. At their second challenge subjects will be assigned to the product not received during their first challenge. The label will include a subject randomization number and information as to which vial should be administered during the first challenge and which should be administered during the second challenge.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Study medication will be provided in vials which are labeled with randomization information only but not contents of vial.
Allocation
Randomized
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Study drug (glucagon) first, placebo second
Arm Type
Other
Arm Description
Each subject will have two mixed meal tolerance tests performed. Each will be randomized to receive either glucagon or matched placebo during the first testing session. A participant could receive 2 doses of the study drug or placebo at each study visit. The opposite treatment will be given during the second testing session after a 1-2 week washout period. Both participants and the study team will be blinded to the intervention being used during each session.
Arm Title
Placebo first, study drug (glucagon) second
Arm Type
Other
Arm Description
Each subject will have two mixed meal tolerance tests performed. Each will be randomized to receive either glucagon or matched placebo during the first testing session. A participant could receive 2 doses of the study drug or placebo at each study visit. The opposite treatment will be given during the second testing session after a 1-2 week washout period. Both participants and the study team will be blinded to the intervention being used during each session.
Intervention Type
Drug
Intervention Name(s)
glucagon
Intervention Description
novel, stable non-aqueous glucagon formulation provided by Xeris Pharmaceuticals
Intervention Type
Device
Intervention Name(s)
Closed loop glucagon pump
Intervention Description
a novel closed-loop glucagon system (CLG) incorporating a novel, stable non-aqueous glucagon formulation together with an infusion pump system (Omnipod) guided by real-time continuous glucose monitoring (Dexcom) that is triggered by a hypoglycemia alert algorithm.
Primary Outcome Measure Information:
Title
Number of Participants With Meal-provoked Hypoglycemia, Defined as Sensor Glucose <65 mg/dL
Description
A primary endpoint for this study is the prevention of meal provoked hypoglycemia, defined as sensor glucose levels below <65 mg/dl, comparing study drug to control.
Time Frame
Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
Title
Number of Participants With Meal-provoked Hypoglycemia, Defined as Plasma Glucose <65 mg/dL
Description
A primary endpoint for this study is prevention of meal provoked hypoglycemia, defined as plasma glucose levels below <65 mg/dl, comparing study drug to control
Time Frame
Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
Secondary Outcome Measure Information:
Title
Number of Participants With Meal-provoked Hypoglycemia, Defined as Sensor Glucose <60 mg/dL
Description
Prevention of meal / provoked hypoglycemia, defined as sensor glucose levels below <60 mg/dl, comparing vehicle to control
Time Frame
Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
Title
Number of Participants With Rebound Hyperglycemia (Defined as Glucose Levels Above 180 mg/dl).
Description
Compare outcomes for glucagon versus vehicle infusions for prevention of rebound hyperglycemia (defined as glucose levels above 180 mg/dl).
Time Frame
Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge will be conducted within two weeks of the first.
Title
Number of Participants With Hypoglycemia Rescue Administered
Description
Protocol-specified rescue delivery of IV glucose was performed if plasma glucose <55 mg/dL and/or significant neuroglycopenia developed.
Time Frame
Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
Title
Number of Participants With Meal-provoked Hypoglycemia, Defined as Plasma Glucose <60 mg/dL
Description
Prevention of meal / provoked hypoglycemia, defined as plasma glucose levels below <60 mg/dl, comparing vehicle to control
Time Frame
Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
Title
Number of Participants With Meal-provoked Hypoglycemia, Defined as Plasma Glucose <55 mg/dL
Description
Prevention of meal / provoked hypoglycemia, defined as plasma glucose levels below <55 mg/dl, comparing vehicle to control
Time Frame
Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
Title
Number of Participants With Meal-provoked Hypoglycemia, Defined as Sensor Glucose <55 mg/dL
Description
Prevention of meal / provoked hypoglycemia, defined as sensor glucose levels below <55 mg/dl, comparing vehicle to control
Time Frame
Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
Title
Percent Time Plasma Glucose in Range After the Final Dose of Study Drug or Vehicle, Which Was Either 1 or 2 Doses Depending on Patient Response
Description
Compare outcomes for glucagon versus vehicle infusions for percent time plasma glucose in range (180-65mg/dL) after the final dose, which was either 1 or 2 doses depending on patient response
Time Frame
Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
Title
Percent Time Sensor Glucose in Range After Drug Delivery After the Final Dose of Study Drug or Vehicle, Which Was Either 1 or 2 Doses Depending on Patient Response
Description
Compare outcomes for glucagon versus vehicle infusions for percent time sensor glucose in range (180-65mg/dL) after the final dose, which was either 1 or 2 doses depending on patient response
Time Frame
Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
Title
Meal Provoked Nadir Plasma Glucose
Description
Nadir plasma glucose (mg/dl) during meal testing, comparing vehicle to control
Time Frame
Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
Title
Meal Provoked Nadir Sensor Glucose
Description
Nadir sensor glucose (mg/dl) during meal testing, comparing vehicle to control
Time Frame
Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
Title
Time to Nadir Plasma Glucose After Mixed Meal (Min)
Time Frame
Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
Title
Time to Nadir Sensor Glucose After Mixed Meal (Min)
Time Frame
Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
Title
Time to Alarm During Mixed Meal Testing (Minutes)
Description
Time to alarm represents the time for the first alarm to occur during mixed meal testing. Alarms are triggered by hypoglycemia (sensor glucose < 65 mg/dL), or by the algorithm predicting that hypoglycemia will occur in less than 30 minutes (taking into account current sensor glucose level (between 65-150 mg/dL) and the rate of change of a rapidly falling sensor glucose level). In the latter case, the alarm is activated even if glucose levels are within the normoglycemic range to allow early detection and response. During both glucagon and vehicle treatment visits, all participants received either 300 μg of glucagon or the equivalent volume of vehicle with the first alarm.
Time Frame
Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
Title
Time to Delivery (Min)
Description
Time to delivery (min) of study drug during mixed meal testing
Time Frame
Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
Title
Sensor Glucose at Time of Alarm 1 During Mixed Meal Testing (mg/dL)
Description
This is the sensor glucose at which time the first alarm occurred during the mixed meal testing. Alarms are triggered by hypoglycemia (sensor glucose < 65 mg/dL), or by the algorithm predicting that hypoglycemia will occur in less than 30 minutes (taking into account current sensor glucose level (between 65-150 mg/dL) and the rate of change of a rapidly falling sensor glucose level). In the latter case, the alarm is activated even if glucose levels are within the normoglycemic range to allow early detection and response. During both glucagon and vehicle treatment visits, all participants received either 300 μg of glucagon or the equivalent volume of vehicle with the first alarm.
Time Frame
Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
Title
Capillary Glucose at Time of Alarm 1 During Mixed Meal Testing (mg/dL)
Description
This is the capillary glucose at which time the first alarm occurred during the mixed meal testing. Alarms are triggered by hypoglycemia (sensor glucose < 65 mg/dL), or by the algorithm predicting that hypoglycemia will occur in less than 30 minutes (taking into account current sensor glucose level (between 65-150 mg/dL) and the rate of change of a rapidly falling sensor glucose level). In the latter case, the alarm is activated even if glucose levels are within the normoglycemic range to allow early detection and response. During both glucagon and vehicle treatment visits, all participants received either 300 μg of glucagon or the equivalent volume of vehicle with the first alarm.
Time Frame
Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
Title
Sensor Glucose at Time of Alarm 2 During Mixed Meal Testing (mg/dL)
Description
This is the sensor glucose at which time the second alarm occurred during the mixed meal testing. Alarms are triggered by hypoglycemia (sensor glucose < 65 mg/dL), or by the algorithm predicting that hypoglycemia will occur in less than 30 minutes (taking into account current sensor glucose level (between 65-150 mg/dL) and the rate of change of a rapidly falling sensor glucose level). In the latter case, the alarm is activated even if glucose levels are within the normoglycemic range to allow early detection and response. During both glucagon and vehicle treatment visits, all participants received either 300 μg of glucagon or the equivalent volume of vehicle with the first alarm.
Time Frame
Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
Title
Capillary Glucose at Time of Alarm 2 During Mixed Meal Testing (mg/dL)
Description
This is the capillary glucose at which time the second alarm occurred during the mixed meal testing. Alarms are triggered by hypoglycemia (sensor glucose < 65 mg/dL), or by the algorithm predicting that hypoglycemia will occur in less than 30 minutes (taking into account current sensor glucose level (between 65-150 mg/dL) and the rate of change of a rapidly falling sensor glucose level). In the latter case, the alarm is activated even if glucose levels are within the normoglycemic range to allow early detection and response. During both glucagon and vehicle treatment visits, all participants received either 300 μg of glucagon or the equivalent volume of vehicle with the first alarm.
Time Frame
Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
Title
Pain Score at Time of First Dose Delivery of Study Drug, Versus Pain Score at Time of First Dose Delivery of Placebo (Comparing First Delivery Pain Scores for Visit Where Participant Received Study Drug vs. Visit Where Participant Received Placebo).
Description
Pain score was assessed verbally, 1 is the least pain (none), 10 is the most severe pain. Pain score at the time of the first administration was compared for the visit where the participant received the study drug vs. the visit where the participant received the placebo. A participant could receive 2 doses of the study drug or placebo at each visit. All 12 participants completed both the study drug phase and the placebo phase. The pain scores for the first administration of study drug vs. first administration of placebo for these two visits were compared. Whether the participant was assigned to the study drug glucagon (vs. placebo) at the first or second MMTT was determined by randomization.
Time Frame
The two study visits where participants were administered either study drug or placebo took place over 2 weeks (there was a 1 to 2 week washout period between visits).
Title
Pain Score at Time of Second Dose Delivery of Study Drug, Versus Pain Score at Time of Second Dose Delivery of Placebo (Comparing Second Delivery Pain Scores for Visit Where Participant Received Study Drug vs. Visit Where Participant Received Placebo).
Description
Pain score was assessed verbally, 1 is the least pain (none), 10 is the most severe pain. Pain score at the time of the second administration was compared for the visit where the participant received the study drug vs. the visit where the participant received the placebo. A participant could receive 2 doses of the study drug or placebo at each visit. All 12 participants completed both the study drug phase and the placebo phase. The pain scores from the second administration of study drug vs. second administration of placebo for these two visits were compared. Whether the participant was assigned to the study drug glucagon (vs. placebo) at the first or second MMTT was determined by randomization.
Time Frame
The two study visits where participants were administered either study drug or placebo took place over 2 weeks (there was a 1 to 2 week washout period between visits).
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Males or females diagnosed with ongoing post-bariatric hypoglycemia with prior episodes of neuroglycopenia, unresponsive to dietary intervention (low glycemic index, controlled carbohydrate portions) and trial of acarbose therapy at the maximally tolerated dose.
Age 18-65 years of age, inclusive, at screening.
Willingness to provide informed consent and follow all study procedures, including attending all scheduled visits.
Exclusion Criteria:
Documented hypoglycemia occurring in the fasting state (> 12 hours fast);
Chronic kidney disease stage 4 or 5 (including end-stage renal disease);
Hepatic disease, including serum alanine transaminase (ALT) or aspartate aminotransferase (AST) greater than or equal to 3 times the upper limit of normal; hepatic synthetic insufficiency as defined as serum albumin < 3.0 g/dL; or serum bilirubin > 2.0;
Congestive heart failure, New York Heart Association (NYHA )class II, III or IV;
History of myocardial infarction, unstable angina or revascularization within the past 6 months or 2 or more risk factors for coronary artery disease including diabetes, uncontrolled hypertension, uncontrolled hyperlipidemia, and active tobacco use;
History of cardiac arrhythmia or arrhythmia detected by EKG during the screening visit;
History of syncope (unrelated to hypoglycemia) or diagnosed cardiac arrhythmia
Concurrent administration of β-blocker therapy;
History of a cerebrovascular accident;
Seizure disorder (other than with suspect or documented hypoglycemia);
Active treatment with any diabetes medications except for acarbose;
Active malignancy, except basal cell or squamous cell skin cancers;
Personal or family history of pheochromocytoma or disorder with increased risk of pheochromocytoma (MEN 2, neurofibromatosis, or Von Hippel-Lindau disease);
Known insulinoma or glucagonoma;
Major surgical operation within 30 days prior to screening;
Hematocrit < 33%;
Bleeding disorder, treatment with warfarin, or platelet count <50,000;
Blood donation (1 pint of whole blood) within the past 2 months;
Active alcohol abuse or substance abuse;
Current administration of oral or parenteral corticosteroids;
Pregnancy and/ or Lactation: For women of childbearing potential: there is a requirement for a negative urine pregnancy test and for agreement to use contraception during the study and for at least 1 month after participating in the study. Acceptable contraception includes birth control pill / patch / vaginal ring, Depo-Provera, Norplant, an intrauterine device (IUD), the double barrier method (the woman uses a diaphragm and spermicide and the man uses a condom), or abstinence;
Use of an investigational drug within 30 days prior to screening;
Current use of anticholinergic medications;
Allergy to a component of the study drug.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mary E Patti, MD
Organizational Affiliation
Joslin Diabetes Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Joslin Diabetes Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
31714583
Citation
Mulla CM, Zavitsanou S, Laguna Sanz AJ, Pober D, Richardson L, Walcott P, Arora I, Newswanger B, Cummins MJ, Prestrelski SJ, Doyle FJ, Dassau E, Patti ME. A Randomized, Placebo-Controlled Double-Blind Trial of a Closed-Loop Glucagon System for Postbariatric Hypoglycemia. J Clin Endocrinol Metab. 2020 Apr 1;105(4):e1260-71. doi: 10.1210/clinem/dgz197.
Results Reference
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Closed-Loop Glucagon Pump for Treatment of Post-Bariatric Hypoglycemia
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