Continuous Glucose Monitoring to Reduce Hypoglycemia and Improve Safety After Gastric Surgery

Study Overview
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Brief Summary
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The purpose of this study is to see if the use of a continuous glucose monitor (CGM) by people who experience low blood sugars (hypoglycemia) after gastric surgery can help reduce the number and severity of low blood sugar episodes.

Detailed Description
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The CGM devices used in this study are approved by the Food and Drug Administration (FDA) for monitoring the glucose levels of people with diabetes. The investigators of this study are looking to see if these CGM devices are able to benefit people who have had gastric surgery and experience low blood sugar episodes, which can be asymptomatic and lead to complications, impairing safety. This study involves wearing a CGM sensor/transmitter during first a masked phase (unable to see CGM sensor glucose levels), followed by an unmasked phase (able to see and respond to sensor glucose levels and alarms). Participants are asked to regularly record fingerstick (capillary) blood sugar values and any symptoms experienced, as well as a record of treatments for symptoms and glucose levels. Participants attend three to five study visits: 5 visits for participants who wore the Dexcom G4, and 3 visits for participants who wore the Dexcom G6. The Dexcom G4 became unavailable during the course of the study when the G6 was introduced. (The Dexcom G4 had a 7 day wear period versus a 10 day wear period for the G6. As the G6 has a longer wear period, the frequency of the study visits was able to be decreased). This study also involves the use of a fitness tracker, which will be worn for the duration of the study and returned at the end of the study. Participants wearing the Dexcom G4 device were able to keep the Dexcom G4 CGM receiver and transmitter (this was not possible with the Dexcom G6 system).

Official Title
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Determining the Efficacy of Continuous Glucose Monitoring to Reduce Hypoglycemia and Improve Safety in Patients With Hypoglycemia After Gastric Surgery

Conditions
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Hypoglycemia, Reactive, Hypoglycemia

Intervention / Treatment
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* Device: Dexcom CGM masked
* Device: Dexcom CGM unmasked


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females diagnosed with ongoing post-bariatric or post-gastric surgery hypoglycemia with prior episodes of neuroglycopenia Age 18-65 years of age, inclusive, at screening 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 (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, Ill 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 syncope (unrelated to hypoglycemia) or diagnosed cardiac arrhythmia Concurrent administration of beta-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 treatment with octreotide or diazoxide; Active malignancy, except basal cell or squamous cell skin cancers; Personal or family history of pheochromocytoma or disorder with increased risk of pheochromocytoma (multiple endocrine neoplasia (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. Acceptable contraception includes birth control pill/patch I 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: The proposed study is designed to assess the efficacy of unmasked personal CGM to reduce the frequency of hypoglycemia after gastric surgery. Specifically, we will analyze glycemic patterns during a phase of baseline masked CGM wear (2 weeks for the Dexcom G4 or 10 days for the Dexcom G6), in comparison to a sequential, second phase of unmasked CGM wear (2 weeks for the Dexcom G4 or 10 days for the Dexcom G6). Please note that we have chosen to have a consistent masked monitoring first, as providing unmasked data to participants first could alter their dietary or other patterns and reduce ability of the study to independently assess efficacy of the CGM intervention.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Masked CGM Wear (Phase 1)<br>Each participant will wear the Dexcom CGM for two sequential phases. During the first phase, participants will not be able to read the sensor glucose levels (masked). | Device: Dexcom CGM masked<br>* The CGM will monitor sensor glucose levels in all participants. (Initially the Dexcom G4 was worn by participants (n=13); however, when the G4 became unavailable, the G6 was worn by the subsequent participants (n=10)). The duration of the Dexcom G4 sensor was 7 days (2 sensors placed during each phase of participation) versus the Dexcom G6 whose sensor duration is 10 days (1 sensor placed during each phase of participation).<br>|
| Experimental: Unmasked CGM Wear (Phase 2)<br>In the second phase, participants will be able to read the sensor glucose levels (unmasked). Frequency of hypoglycemia will be compared between the two phases of the study. | Device: Dexcom CGM unmasked<br>* During the second phase (2 weeks for the Dexcom G4 and 10 days for the Dexcom G6), participants are able to see the sensor glucose levels displayed from the CGM. Participants will be instructed to use this information to treat low glucose levels before symptoms or severely low glucose levels develop. The duration of the Dexcom G4 sensor was 7 days (2 sensors placed during each phase of participation) versus the Dexcom G6 whose sensor duration is 10 days (1 sensor placed during each phase of participation).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Time Sensor Glucose <70 mg/dL in the Masked Versus the Unmasked Phase. | The primary outcome will be time spent in hypoglycemic glucose range as measured by percent time sensor glucose is <70 mg/dl, comparing the masked versus the unmasked phases. | 28 days for those participants wearing Dexcom G4, and 20 days for participants wearing Dexcom G6. | 
| Percentage of Time Sensor Glucose <60mg/dL in the Masked Versus the Unmasked Phase | The primary outcome will be time spent in hypoglycemic glucose range as measured by percent time sensor glucose is <60 mg/dl, comparing the masked versus the unmasked phases. | 28 days for those participants wearing Dexcom G4, and 20 days for participants wearing Dexcom G6. | 
| Percentage of Time Sensor Glucose <54 mg/dL in the Masked Versus the Unmasked Phase | The primary outcome will be time spent in hypoglycemic glucose range as measured by percent time sensor glucose is <60 mg/dl, comparing the masked versus the unmasked phases. | 28 days for those participants wearing Dexcom G4, and 20 days for participants wearing Dexcom G6. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Sensor Glucose Level During Masked Versus Unmasked Phases of Wear |  | 28 days for those participants wearing Dexcom G4, and 20 days for participants wearing Dexcom G6. | 
| Mean Sensor Glucose Level During Masked Versus Unmasked Phases of Wear |  | 28 days for those participants wearing Dexcom G4, and 20 days for participants wearing Dexcom G6. | 
| Peak Sensor Glucose Level During Masked Versus Unmasked Period of CGM Wear | expressed as median and median standard deviation | 28 days for those participants wearing Dexcom G4, and 20 days for participants wearing Dexcom G6. | 
| Sensor Glucose Level Range (Highest Sensor Glucose Minus Lowest Sensor Glucose mg/dL) During Masked Versus Unmasked Period of CGM Wear | The sensor glucose level range is derived from the difference between the highest sensor glucose levels minus the lowest sensor glucose level (mg/dL). | 28 days for those participants wearing Dexcom G4, and 20 days for participants wearing Dexcom G6. | 
| Nadir Sensor Glucose Level During Masked Versus Unmasked Period of CGM Wear |  | 28 days for those participants wearing Dexcom G4, and 20 days for participants wearing Dexcom G6. | 
| Percent of Time Sensor Glucose 70-180 mg/dL During Period of CGM Wear, Masked Versus Unmasked Phase |  | 28 days for those participants wearing Dexcom G4, and 20 days for participants wearing Dexcom G6. | 
| Percentage of Time Sensor Glucose Level >180 mg/dL During Period of CGM Wear, Masked Versus Unmasked Phase |  | 28 days for those participants wearing Dexcom G4, and 20 days for participants wearing Dexcom G6. | 
| Percentage of Time Sensor Glucose Level >250 mg/dL During Periods of CGM Wear, Masked Versus Unmasked Phase |  | 28 days for those participants wearing Dexcom G4, and 20 days for participants wearing Dexcom G6. | 
| Glycemic Variability as Measured by the Standard Deviation of Sensor Glucose Level Data During Periods of CGM Wear, Masked Versus Unmasked Phase |  | 28 days for those participants wearing Dexcom G4, and 20 days for participants wearing Dexcom G6. | 
| Mean Coefficient of Variation of Sensor Glucose Data During Period of CGM Wear, Masked Versus Unmasked Phase |  | 28 days for those participants wearing Dexcom G4, and 20 days for participants wearing Dexcom G6. | 
| Mean Amplitude of Glycemic Excursion (MAGE) of Sensor Glucose Levels During Periods of CGM Wear, Masked Versus Unmasked Phase |  | 28 days for those participants wearing Dexcom G4, and 20 days for participants wearing Dexcom G6. | 
| 24 Hour Continuous Overall Net Glycemic Action (CONGA) for Sensor Glucose Data During Periods of CGM Wear, Masked Versus Unmasked Phase | CONGA assesses glucose variability within a predetermined time window - 24 hours in this case. Calculation of this parameter is based on the assessment of the differences between glucose values measured at regular time intervals, then on the standard deviation (SD) of these differences | 28 days for those participants wearing Dexcom G4, and 20 days for participants wearing Dexcom G6. | 
| 1 Hour Continuous Overall Net Glycemic Action (CONGA) for Sensor Glucose Data During Periods of CGM Wear, Masked Versus Unmasked Phase |  | 28 days for those participants wearing Dexcom G4, and 20 days for participants wearing Dexcom G6. | 
| 2 Hours, Continuous Overall Net Glycemic Action (CONGA) for Sensor Glucose Data During Periods of CGM Wear, Masked Versus Unmasked Phase |  | 28 days for those participants wearing Dexcom G4, and 20 days for participants wearing Dexcom G6. | 
| 4 Hours, Continuous Overall Net Glycemic Action (CONGA) for Sensor Glucose Data During Periods of CGM Wear, Masked Versus Unmasked Phase |  | 28 days for those participants wearing Dexcom G4, and 20 days for participants wearing Dexcom G6. | 
| Total Number of Hypoglycemic Events During the Masked Versus the Unmasked Phases of CGM Wear, as Defined by a Sensor Glucose <70 mg/dL, for at Least 15 Minutes | Hypoglycemic events are defined as having glucose <70 mg/dL for at least 15 minutes, ending when glucose > the threshold. Hypoglycemic event values were normalized by dividing the number of events by the number of days of data. | 28 days for those participants wearing Dexcom G4, and 20 days for participants wearing Dexcom G6. | 
| Total Number of Hypoglycemic Events Defined by a Sensor Glucose <60 mg/dL, for at Lease 15 Minutes, During the Masked Versus Unmasked CGM Phase | Hypoglycemic events are defined as having glucose <60 mg/dL for at least 15 minutes, ending when glucose > the threshold. Hypoglycemic event values were normalized by dividing the number of events by the number of days of data. | 28 days for those participants wearing Dexcom G4, and 20 days for participants wearing Dexcom G6. | 
| Total Number of Hypoglycemic Events Defined by a Sensor Glucose <54 mg/dL, for at Least 15 Minutes, During the Masked Versus Unmasked CGM Phase | Hypoglycemic events are defined as having glucose <54 mg/dL for at least 15 minutes, ending when glucose > the threshold. Hypoglycemic event values were normalized by dividing the number of events by the number of days of data. | 28 days for those participants wearing Dexcom G4, and 20 days for participants wearing Dexcom G6. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Post-bariatric Hypoglycemia;