Complications of Bariatric Procedures, Hypoglycemia
Conditions
Keywords
hypoglycemia, glucagon, glucose metabolism disorders, hormones, gastrointestinal agents, bariatric surgery, incretins
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.
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.
Interventions
0.15 or 0.3 mg G-Pump™ (glucagon infusion) administered from OmniPod® pump
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Xeris Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Detection/Notification of Hypoglycemia | 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Severe Hypoglycemia | 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. |
| Number of Subjects With Rebound Hyperglycemia | 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. |
| Glucose Time in Range | 0 - 120 minutes following dosing | Time glucose remains in goal range, 60-180 mg/dl, reported in minutes |
Countries
United States
Participant flow
Pre-assignment details
A total of 8 patients were enrolled in the study. One subject withdrew prior to completing study procedures, leaving 7 subjects who were assigned to a treatment arm. Consistent with the number of subjects who started treatment period 1, the number enrolled is given as 7 even though demographics are presented for all 8 qualified/enrolled subjects.
Participants by arm
| Arm | Count |
|---|---|
| G-Pump™ (Glucagon Infusion) 0.15 or 0.3 mg G-Pump™ (glucagon infusion) administered from OmniPod® pump
G-Pump™ (glucagon infusion): 0.15 or 0.3 mg G-Pump™ (glucagon infusion) administered from OmniPod® pump | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | G-Pump™ (Glucagon Infusion) |
|---|---|
| Age, Continuous | 51 years |
| Current BMI | 30.1 kg/m2 |
| Delta BMI | -16.3 kg/m2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Hemoglobin A1c | 5.7 % |
| Months postop at study visit | 116 months |
| Months postop hypoglycemia diagnosed | 41 months |
| Preoperative Body Mass Index (BMI) | 46.4 kg/m2 |
| Prescribed glucose-modifying medications | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Received nutritional counseling | 7 Participants |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 7 |
| other Total, other adverse events | 7 / 7 |
| serious Total, serious adverse events | 0 / 7 |
Outcome results
Primary
Detection/Notification of Hypoglycemia
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.
Time frame: 0 - 120 minutes following dosing
Population: Includes all subjects who completed a study visit, including repeat visits by 2 subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| G-Pump™ (Glucagon Infusion) | Detection/Notification of Hypoglycemia | 9 successful events |
Secondary
Glucose Time in Range
Time glucose remains in goal range, 60-180 mg/dl, reported in minutes
Time frame: 0 - 120 minutes following dosing
Population: Includes all subjects who completed a study visit, including repeat visits by 2 subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| G-Pump™ (Glucagon Infusion) | Glucose Time in Range | 113 Minutes | Standard Deviation 11 |
Secondary
Number of Subjects With Rebound Hyperglycemia
Frequency of rebound hyperglycemia defined as glucose levels above 180 mg/dl. Reported as the number of subjects with rebound hyperglycemia.
Time frame: 0 - 120 minutes following dosing
Population: Includes all subjects who completed a study visit, including repeat visits by 2 subjects.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| G-Pump™ (Glucagon Infusion) | Number of Subjects With Rebound Hyperglycemia | 0 Participants |
Secondary
Number of Subjects With Severe Hypoglycemia
Frequency of severe hypoglycemia defined as glucose levels below 60 mg/dl. Reported as the number of subjects with severe hypoglycemia.
Time frame: 0 - 120 minutes following dosing
Population: Includes all subjects who completed a study visit, including repeat visits by 2 subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| G-Pump™ (Glucagon Infusion) | Number of Subjects With Severe Hypoglycemia | 3 participants |