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

NCT03255629 | Completed Phase 1 Results FDA Drug FDA Device

• 2 other identifiers: 2016-271R44DK107114
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Post-bariatric Hypoglycemia

Outcome Measures

Primary Outcomes (2)

• 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 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 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

  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).

  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

  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

  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

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

Study Arms (2)

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.

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.

Device: Closed loop glucagon pump

Interventions

glucagon DRUG

novel, stable non-aqueous glucagon formulation provided by Xeris Pharmaceuticals

Study drug (glucagon) first, placebo second

Closed loop glucagon pump DEVICE

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.

Placebo first, study drug (glucagon) second; Study drug (glucagon) first, placebo second

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Joslin Diabetes Center: lead
• National Institutes of Health (NIH): collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Xeris Pharmaceuticals: collaborator
• Harvard University: collaborator

Study Sites (1)

Joslin Diabetes Center

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• 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.

  PMID: 31714583 BACKGROUND

MeSH Terms

Interventions

Glucagon

Intervention Hierarchy (Ancestors)

Proglucagon; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Mary Elizabeth Patti, MD
• Organization: Joslin Diabetes Center

MaryElizabeth.Patti@joslin.harvard.edu

(617) 309-2635

Study Officials

• Mary E Patti, MD

  Joslin Diabetes Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study medication will be provided in vials which are labeled with randomization information only but not contents of vial.
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 10, 2017
• First Posted: August 21, 2017
• Study Start: September 19, 2017
• Primary Completion: August 22, 2018
• Study Completion: August 22, 2018
• Last Updated: September 6, 2022
• Results First Posted: July 26, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)