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Trial · Interventional

CompletedPhase 1/2Results postedRegistry data

Closed-Loop Glucagon Pump for Treatment of Post-Bariatric Hypoglycemia

NCTNCT03255629 (opens ClinicalTrials.gov in a new tab)Other id2016-27Other id1R44DK107114
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 1/2
Enrollment
18 participants (actual)
Sponsor
Joslin Diabetes Center · Other
Design
Randomized · Quadruple masking
Countries
1 country

United States

Start
19 Sept 2017
Primary completion
22 Aug 2018
Completion
22 Aug 2018
First posted
21 Aug 2017
Last update posted
6 Sept 2022
Conditions
Post-bariatric Hypoglycemia

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
201720182019
  1. Ph 1/2

    Closed-Loop Glucagon Pump for Treatment of Post-Bariatric Hypoglycemia

    NCT03255629

    19 Sept 2017 to 22 Aug 2018

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • glucagonDrug
  • Closed loop glucagon pumpDevice

Arms2

  • Other

    Study drug (glucagon) first, placebo second

    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.

  • Other

    Placebo first, study drug (glucagon) second

    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.

Primary outcomes2

Outcomes the sponsor listed as primary.

  1. Number of Participants With Meal-provoked Hypoglycemia, Defined as Sensor Glucose <65 mg/dL

    Time frame · Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

    Registry 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.

  2. Number of Participants With Meal-provoked Hypoglycemia, Defined as Plasma Glucose <65 mg/dL

    Time frame · Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

    Registry 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

Secondary outcomes(20)

  1. Number of Participants With Meal-provoked Hypoglycemia, Defined as Sensor Glucose <60 mg/dL

    Time frame · Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

    Registry description

    Prevention of meal / provoked hypoglycemia, defined as sensor glucose levels below \<60 mg/dl, comparing vehicle to control

  2. Number of Participants With 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.

    Registry description

    Compare outcomes for glucagon versus vehicle infusions for prevention of rebound hyperglycemia (defined as glucose levels above 180 mg/dl).

  3. Number of Participants With Hypoglycemia Rescue Administered

    Time frame · Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

    Registry description

    Protocol-specified rescue delivery of IV glucose was performed if plasma glucose \<55 mg/dL and/or significant neuroglycopenia developed.

  4. Number of Participants With Meal-provoked Hypoglycemia, Defined as Plasma Glucose <60 mg/dL

    Time frame · Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

    Registry description

    Prevention of meal / provoked hypoglycemia, defined as plasma glucose levels below \<60 mg/dl, comparing vehicle to control

  5. Number of Participants With Meal-provoked Hypoglycemia, Defined as Plasma Glucose <55 mg/dL

    Time frame · Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

    Registry description

    Prevention of meal / provoked hypoglycemia, defined as plasma glucose levels below \<55 mg/dl, comparing vehicle to control

  6. Number of Participants With Meal-provoked Hypoglycemia, Defined as Sensor Glucose <55 mg/dL

    Time frame · Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

    Registry description

    Prevention of meal / provoked hypoglycemia, defined as sensor glucose levels below \<55 mg/dl, comparing vehicle to control

  7. 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

    Time frame · Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

    Registry 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

  8. 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

    Time frame · Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

    Registry 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

  9. Meal Provoked Nadir Plasma Glucose

    Time frame · Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

    Registry description

    Nadir plasma glucose (mg/dl) during meal testing, comparing vehicle to control

  10. Meal Provoked Nadir Sensor Glucose

    Time frame · Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

    Registry description

    Nadir sensor glucose (mg/dl) during meal testing, comparing vehicle to control

  11. 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.

  12. 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.

  13. Time to Alarm During Mixed Meal Testing (Minutes)

    Time frame · Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

    Registry 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.

  14. Time to Delivery (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.

    Registry description

    Time to delivery (min) of study drug during mixed meal testing

  15. Sensor Glucose at Time of Alarm 1 During Mixed Meal Testing (mg/dL)

    Time frame · Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

    Registry 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.

  16. Capillary Glucose at Time of Alarm 1 During Mixed Meal Testing (mg/dL)

    Time frame · Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

    Registry 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.

  17. Sensor Glucose at Time of Alarm 2 During Mixed Meal Testing (mg/dL)

    Time frame · Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

    Registry 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.

  18. Capillary Glucose at Time of Alarm 2 During Mixed Meal Testing (mg/dL)

    Time frame · Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

    Registry 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.

  19. 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).

    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).

    Registry 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.

  20. 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).

    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).

    Registry 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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeNumber· Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

Number of Participants With Meal-provoked Hypoglycemia, Defined as Sensor Glucose <65 mg/dL

GroupValue (participants)
Study Drug (Glucagon) Phase1
Placebo / Control Phase5
Primary outcomeCount of participants· Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

Number of Participants With Meal-provoked Hypoglycemia, Defined as Plasma Glucose <65 mg/dL

GroupValue (Participants)
Study Drug (Glucagon) Phase1
Placebo / Control Phase4
Secondary and other outcome results(6)
Secondary outcomeCount of participants· Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

Number of Participants With Meal-provoked Hypoglycemia, Defined as Sensor Glucose <60 mg/dL

GroupValue (Participants)
Study Drug (Glucagon) Phase1
Placebo / Control Phase3
Secondary outcomeCount of participants· Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge will be conducted within two weeks of the first.

Number of Participants With Rebound Hyperglycemia (Defined as Glucose Levels Above 180 mg/dl).

GroupValue (Participants)
Study Drug (Glucagon) Phase0
Placebo / Control Phase0
Secondary outcomeCount of participants· Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

Number of Participants With Hypoglycemia Rescue Administered

GroupValue (Participants)
Study Drug (Glucagon) Phase0
Placebo / Control Phase7
Secondary outcomeCount of participants· Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

Number of Participants With Meal-provoked Hypoglycemia, Defined as Plasma Glucose <60 mg/dL

GroupValue (Participants)
Study Drug (Glucagon) Phase0
Placebo / Control Phase3
Secondary outcomeCount of participants· Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

Number of Participants With Meal-provoked Hypoglycemia, Defined as Plasma Glucose <55 mg/dL

GroupValue (Participants)
Study Drug (Glucagon) Phase0
Placebo / Control Phase5
Secondary outcomeCount of participants· Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

Number of Participants With Meal-provoked Hypoglycemia, Defined as Sensor Glucose <55 mg/dL

GroupValue (Participants)
Study Drug (Glucagon) Phase0
Placebo / Control Phase0

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Treatment Arm and Control Arm (Randomized, Double-Blind, Placebo-Controlled Crossover Design)Each subject had two mixed meal tolerance tests performed. Each was randomized to receive either glucagon or matched placebo during the first testing session. The opposite treatment was given during the second testing session. Both participants and the study team were blinded to the intervention being used during each session. glucagon: novel, stable non-aqueous glucagon formulation provided by Xeris Pharmaceuticals Closed loop glucagon pump: 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.0 / 181 / 1816 / 18

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years up to 65 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: 1. 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. 2. Age 18-65 years of age, inclusive, at screening. 3. Willingness to provide informed consent and follow all study procedures, including attending all scheduled visits. Exclusion Criteria: 1. Documented hypoglycemia occurring in the fasting state (\> 12 hours fast); 2. Chronic kidney disease stage 4 or 5 (including end-stage renal disease); 3. 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; 4. Congestive heart failure, New York Heart Association (NYHA )class II, III or IV; 5. 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; 6. History of cardiac arrhythmia or arrhythmia detected by EKG during the screening visit; 7. History of syncope (unrelated to hypoglycemia) or diagnosed cardiac arrhythmia 8. Concurrent administration of β-blocker therapy; 9. History of a cerebrovascular accident; 10. Seizure disorder (other than with suspect or documented hypoglycemia); 11. Active treatment with any diabetes medications except for acarbose; 12. Active malignancy, except basal cell or squamous cell skin cancers; 13. Personal or family history of pheochromocytoma or disorder with increased risk of pheochromocytoma (MEN 2, neurofibromatosis, or Von Hippel-Lindau disease); 14. Known insulinoma or glucagonoma; 15. Major surgical operation within 30 days prior to screening; 16. Hematocrit \< 33%; 17. Bleeding disorder, treatment with warfarin, or platelet count \<50,000; 18. Blood donation (1 pint of whole blood) within the past 2 months; 19. Active alcohol abuse or substance abuse; 20. Current administration of oral or parenteral corticosteroids; 21. 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; 22. Use of an investigational drug within 30 days prior to screening; 23. Current use of anticholinergic medications; 24. Allergy to a component of the study drug.

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