Post-bariatric HypoglycemiaPhase 1/2NCT03255629
Closed-Loop Glucagon Pump for Treatment of Post-Bariatric Hypoglycemia
A Phase 1/2 study testing glucagon and Closed loop glucagon pump in people with Post-bariatric Hypoglycemia, run by Joslin Diabetes Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Post-bariatric Hypoglycemia
- What is being tested?
- glucagon and Closed loop glucagon pump
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Sep 2017to 22 Aug 2018
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
Show all 24Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Post-bariatric Hypoglycemia
- Being tested
- glucagon, Closed loop glucagon pump
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
glucagonDrug
novel, stable non-aqueous glucagon formulation provided by Xeris Pharmaceuticals
Closed loop glucagon pumpDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Study drug (glucagon) first, placebo second | Other | 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. Receives: Drug: glucagon; Device: Closed loop glucagon pump |
| Placebo first, study drug (glucagon) second | Other | 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. Receives: Device: Closed loop glucagon pump |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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
Measured: Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
Secondary outcomes (20)
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
Measured: 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 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).
Measured: 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 Hypoglycemia Rescue Administered
Protocol-specified rescue delivery of IV glucose was performed if plasma glucose <55 mg/dL and/or significant neuroglycopenia developed.
Measured: 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
Prevention of meal / provoked hypoglycemia, defined as plasma glucose levels below <60 mg/dl, comparing vehicle to control
Measured: 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
Prevention of meal / provoked hypoglycemia, defined as plasma glucose levels below <55 mg/dl, comparing vehicle to control
Measured: 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
Prevention of meal / provoked hypoglycemia, defined as sensor glucose levels below <55 mg/dl, comparing vehicle to control
Measured: Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
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
Measured: Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
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
Measured: Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
Meal Provoked Nadir Plasma Glucose
Nadir plasma glucose (mg/dl) during meal testing, comparing vehicle to control
Measured: Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
Meal Provoked Nadir Sensor Glucose
Nadir sensor glucose (mg/dl) during meal testing, comparing vehicle to control
Measured: Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
Time to Nadir Plasma Glucose After Mixed Meal (Min)
Measured: Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
Time to Nadir Sensor Glucose After Mixed Meal (Min)
Measured: Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
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.
Measured: Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
Time to Delivery (Min)
Time to delivery (min) of study drug during mixed meal testing
Measured: Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
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.
Measured: Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
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.
Measured: Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
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.
Measured: Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
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.
Measured: Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
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.
Measured: 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).
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.
Measured: 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).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2017
- Study start19 Sep 2017
- Primary completion22 Aug 2018
- Study completion22 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Post-bariatric HypoglycemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Joslin Diabetes Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Xeris Pharmaceuticals, Harvard University
- Responsible party
- Sponsor
- Investigators
- Mary E Patti, MD, Principal investigator, Joslin Diabetes Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03255629
- Sponsor's protocol ID
- 2016-27
- Other IDs
- 1R44DK107114
- Status last verified
- Aug 2022
- First submitted
- 10 Aug 2017
- Last updated
- 6 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 31714583
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Closed-Loop Glucagon Pump for Treatment of Post-Bariatric Hypoglycemia
- ClinicalTrials.gov ID
- NCT03255629
- Acronym / sponsor ID
- 2016-27
- Conditions
- Post-bariatric Hypoglycemia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Joslin Diabetes CenterUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Xeris Pharmaceuticals, Harvard University
- Study start
- 19 Sep 2017 (actual)
- Primary completion
- 22 Aug 2018 (actual)
- Study completion
- 22 Aug 2018 (actual)
- First posted
- 21 Aug 2017 (actual)
- Results
- Posted 26 Jul 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Study drug (glucagon) first, placebo second | Other | Drug: glucagon, Device: Closed loop glucagon pumpEach 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. |
| Placebo first, study drug (glucagon) second | Other | Device: Closed loop glucagon pumpEach 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (24 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| glucagonnovel, stable non-aqueous glucagon formulation provided by Xeris Pharmaceuticals | Drug | Study drug (glucagon) first, placebo second |
| Closed loop glucagon pumpa 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. | Device | Placebo first, study drug (glucagon) second, Study drug (glucagon) first, placebo second |
Primary outcome
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.
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
Time frame: Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.
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
20 secondary outcomes
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 31714583Mulla 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.
- Individual participant dataSharing planned: No
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Dietary, Medication, and Endoscopic Interventions for Post-Bariatric Hypoglycemia
Post-Bariatric Hypoglycemia
Active, not recruitingPhase 2
Pasireotide s.c. in Patients With Post-Bariatric Hypoglycaemia
Post-Bariatric Hypoglycemia
Not yet recruiting
Continuous Glucose Monitoring in Metabolic Surgery
Obesity (Disorder)
RecruitingPhase 4
Post-Prandial Carbohydrate Metabolism in Individuals With and Without Post-Bariatric Surgery Hypoglycemia (PBH)
Hypoglycemia, Hypoglycemia, Reactive
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mary E Patti, MD principal investigator
Joslin Diabetes Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing glucagon and Closed loop glucagon pump in people with Post-bariatric Hypoglycemia, run by Joslin Diabetes Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Jul 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03255629, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Sep 2022.