Delivery of G-Pump™ (Glucagon Infusion) From an OmniPod® to Prevent Hypoglycemia in Post-Bariatric Surgery Patients

• ClinicalTrials.gov Identifier: NCT02733588
• Recruitment Status: Completed
• First Posted: April 11, 2016
• Results First Posted: October 30, 2018
• Last Update Posted: October 30, 2018
• Sponsor: Xeris Pharmaceuticals
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): Xeris Pharmaceuticals

Study Description

Brief Summary:

The primary objective of this study is to test an optimized control system for sensor-guided (physician administered) delivery of glucagon, and test Proof-of-Concept (POC) in a clinical setting in patients with severe hypoglycemia following bariatric surgery.

Condition or disease	Intervention/treatment	Phase
Hypoglycemia; Complications of Bariatric Procedures	Drug: G-Pump™ (glucagon infusion)	Phase 2

Detailed Description:

This is a Phase 2a, single-center, open-label, proof-of-concept study designed to test the ability of the control algorithm to detect and direct timing of G-Pump™ glucagon infused from an OmniPod® pump to prevent hypoglycemia in patients with post-bariatric hypoglycemia syndrome. While the algorithm will provide an alert as to when glucagon should be dosed to prevent hypoglycemia, there will be no automation in this clinical trial and it will ultimately be up to the physician to initiate dosing via the OmniPod® controller.

Participant on continuous glucose monitoring will arrive at the clinic and IV line will be inserted for venous access. Subject will then be asked to drink a liquid mixed meal containing 60 g of carbohydrates, e.g. Boost® Nutritional Drink, over 10 minutes. Blood samples will be collected for glucose and hormone measurement.

The open-loop system will be set to recognize low sensor glucose values, triggering an alert to the physician, who will deliver a bolus of 150 or 300 µg of glucagon via the pump, with the goal of preventing further decline in glucose values. Depending on response, a second bolus dose of 150 or 300 µg of glucagon may be administered. Plasma glucose will be measured after glucagon administration to ensure successful treatment and glucose stability, and glucagon levels will be analyzed concurrently to determine magnitude of increase above baseline. Sensors will be downloaded for subsequent analysis of appropriateness of alert timing and trigger for glucagon bolus delivery.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Proof-of-Concept Study of Sensor-Guided, Clinician-Administered Delivery of G-Pump™ (Glucagon Infusion) From an OmniPod® to Prevent Post-Prandial Hypoglycemia in Post-Bariatric Surgery Patients
• Study Start Date: March 2016
• Actual Primary Completion Date: April 5, 2017
• Actual Study Completion Date: June 1, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: G-Pump™ (glucagon infusion); 0.15 or 0.3 mg G-Pump™ (glucagon infusion) administered from OmniPod® pump	Drug: G-Pump™ (glucagon infusion); 0.15 or 0.3 mg G-Pump™ (glucagon infusion) administered from OmniPod® pump; Other Name: glucagon

Outcome Measures

Primary Outcome Measures :

1. Detection/Notification of Hypoglycemia [ Time Frame: 0 - 120 minutes following dosing ]
   Frequency with which the device controller software correctly identifies impending hypoglycemia (glucose < 75 mg/dl) and notifies the investigator to initiate treatment. Reported as the number of successful identifications.

Secondary Outcome Measures :

1. Number of Subjects With Severe Hypoglycemia [ Time Frame: 0 - 120 minutes following dosing ]
   Frequency of severe hypoglycemia defined as glucose levels below 60 mg/dl. Reported as the number of subjects with severe hypoglycemia.
2. Number of Subjects With Rebound Hyperglycemia [ Time Frame: 0 - 120 minutes following dosing ]
   Frequency of rebound hyperglycemia defined as glucose levels above 180 mg/dl. Reported as the number of subjects with rebound hyperglycemia.
3. Glucose Time in Range [ Time Frame: 0 - 120 minutes following dosing ]
   Time glucose remains in goal range, 60-180 mg/dl, reported in minutes

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 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.
• 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;
• hepatic disease, including serum alanine aminotransferase or aspartate aminotransferase 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 class II, III or IV;
• history of myocardial infarction, unstable angina or revascularization within the past 6 months;
• 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;
• 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.
• use of an investigational drug within 30 days prior to screening.
• there will be no involvement of special vulnerable populations such as pregnant women, prisoners, institutionalized or incarcerated individuals, or others who may be considered vulnerable populations.

Contacts and Locations

Locations

United States, Massachusetts

Joslin Diabetes Center

Boston, Massachusetts, United States, 02215

Sponsors and Collaborators

Xeris Pharmaceuticals

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  Study Documents (Full-Text)

Documents provided by Xeris Pharmaceuticals:

Study Protocol  [PDF] February 13, 2017

Statistical Analysis Plan  [PDF] February 13, 2017

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Laguna Sanz AJ, Mulla CM, Fowler KM, Cloutier E, Goldfine AB, Newswanger B, Cummins M, Deshpande S, Prestrelski SJ, Strange P, Zisser H, Doyle FJ 3rd, Dassau E, Patti ME. Design and Clinical Evaluation of a Novel Low-Glucose Prediction Algorithm with Mini-Dose Stable Glucagon Delivery in Post-Bariatric Hypoglycemia. Diabetes Technol Ther. 2018 Feb;20(2):127-139. doi: 10.1089/dia.2017.0298.

• Responsible Party: Xeris Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02733588
• Other Study ID Numbers: XSGO-PB01; 1R44DK107114-01 ( U.S. NIH Grant/Contract )
• First Posted: April 11, 2016
• Results First Posted: October 30, 2018
• Last Update Posted: October 30, 2018
• Last Verified: October 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Xeris Pharmaceuticals:

hypoglycemia; glucagon; glucose metabolism disorders; hormones; gastrointestinal agents; bariatric surgery; incretins

Additional relevant MeSH terms:

Hypoglycemia; Glucose Metabolism Disorders; Metabolic Diseases; Glucagon; Glucagon-Like Peptide 1; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Incretins