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

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

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03353415

Enrollment

Registered

2017-11-27

Start date

2019-02-07

Completion date

2023-04-12

Last updated

2023-08-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hypoglycemia, Hypoglycemia, Reactive

Keywords

Post-bariatric Hypoglycemia;

Brief summary

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

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).

Interventions

DEVICEDexcom CGM unmasked

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).

DEVICEDexcom CGM masked

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).

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Masking description

The proposed study is designed to assess the efficacy of unmasked personal CGM to reduce the frequency of hypoglycemia after gastric surgery. Participants themselves will not be masked to study design. The only masking will be of the device sensor glucose data during the first 2 weeks (Dexcom G4) or 10 days (Dexcom G6) of the study.

Intervention 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.

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Inclusion criteria

1. Males or females diagnosed with ongoing post-bariatric or post-gastric surgery hypoglycemia with prior episodes of neuroglycopenia 2. Age 18-65 years of age, inclusive, at screening 3. Willingness to provide informed consent and follow all study procedures, including attending all scheduled visits.

Exclusion criteria

1. Documented hypoglycemia occurring in the fasting state (\> 12 hours fast); 2. Chronic kidney disease stage 4 or 5 (including end-stage renal disease); 3. 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; 4. Congestive heart failure, New York Heart Association (NYHA) class II, Ill or IV; 5. 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. 6. History of syncope (unrelated to hypoglycemia) or diagnosed cardiac arrhythmia 7. Concurrent administration of beta-blocker therapy; 8. History of a cerebrovascular accident; 9. Seizure disorder (other than with suspect or documented hypoglycemia); 10. Active treatment with any diabetes medications except for acarbose; 11. Active treatment with octreotide or diazoxide; 12. Active malignancy, except basal cell or squamous cell skin cancers; 13. Personal or family history of pheochromocytoma or disorder with increased risk of pheochromocytoma (multiple endocrine neoplasia (MEN) 2, neurofibromatosis, or Von Hippel-Lindau disease); 14. Known insulinoma; 15. Major surgical operation within 30 days prior to screening; 16. Hematocrit\< 33%; 17. Bleeding disorder, treatment with warfarin, or platelet count \<50,000; 18. Blood donation (1 pint of whole blood) within the past 2 months; 19. Active alcohol abuse or substance abuse; 20. Current administration of oral or parenteral corticosteroids; 21. 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. 22. Use of an investigational drug within 30 days prior to screening.

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Time Sensor Glucose <70 mg/dL in the Masked Versus the Unmasked Phase.	28 days for those participants wearing Dexcom G4, and 20 days for participants wearing Dexcom G6.	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.
Percentage of Time Sensor Glucose <60mg/dL in the Masked Versus the Unmasked Phase	28 days for those participants wearing Dexcom G4, and 20 days for participants wearing Dexcom G6.	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.
Percentage of Time Sensor Glucose <54 mg/dL in the Masked Versus the Unmasked Phase	28 days for those participants wearing Dexcom G4, and 20 days for participants wearing Dexcom G6.	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.

Secondary

Measure	Time frame	Description
Sensor Glucose Level Range (Highest Sensor Glucose Minus Lowest Sensor Glucose mg/dL) During Masked Versus Unmasked Period of CGM Wear	28 days for those participants wearing Dexcom G4, and 20 days for participants wearing Dexcom G6.	The sensor glucose level range is derived from the difference between the highest sensor glucose levels minus the lowest sensor glucose level (mg/dL).
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.	—
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.	—
24 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.	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
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	28 days for those participants wearing Dexcom G4, and 20 days for participants wearing Dexcom G6.	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.
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	28 days for those participants wearing Dexcom G4, and 20 days for participants wearing Dexcom G6.	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.
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	28 days for those participants wearing Dexcom G4, and 20 days for participants wearing Dexcom G6.	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.
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.	—
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	28 days for those participants wearing Dexcom G4, and 20 days for participants wearing Dexcom G6.	expressed as median and median standard deviation

Countries

United States

Participant flow

Recruitment details

Patients with post-gastric surgery hypoglycemia were recruited from the Hypoglycemia Clinic at Joslin Diabetes Center, directed by Dr. Patti. The study was explained to potential participants initially in the clinical setting or during a subsequent telephone screening session. Recruitment took place between February of 2019 through December of 2021. The dexcom G4 was available for the first 13 participants. The remaining 10 participants wore the dexcom G6.

Pre-assignment details

After enrollment, 1 participant was withdrawn and did not complete baseline evaluation (visit 1) due to hospitalization. Following baseline evaluation (visit 1), 2 participants were lost to followup and did not complete the masked CGM wear period. One additional participant was excluded due to missing data and therefore could not be included in the analyses.

Participants by arm

Arm	Count
CGM Use Each participant wore the Dexcom continuous glucose monitor (CGM) available at their time of participation. The Dexcom G4 became unavailable during the course of the study and later participants wore the Dexcom G6. During the first two weeks (Dexcom G4) or first 10 days (Dexcom G6), participants were not able to read the sensor glucose levels. In the second two weeks (Dexcom G4) or second 10 days (Dexcom G6), participants were able to read the sensor glucose levels. Frequency of hypoglycemia was compared between the two phases of the study (masked versus unmasked CGM). Dexcom CGM: The CGM monitored sensor glucose levels in all participants. During the first two weeks (Dexcom G4) or first 10 days (Dexcom G6) of the study, participants were masked to the sensor glucose levels and needed to use other methods, such as a blood sample from a finger stick, to check their blood sugar. During the second two weeks (Dexcom G4) or second10 days (Dexcom G6), participants were able to see the sensor glucose levels displayed from the CGM. Participants were instructed to use this information to treat low glucose levels before symptoms or severely low glucose levels developed.	25
Total	25

Arm

Count

CGM Use

Each participant wore the Dexcom continuous glucose monitor (CGM) available at their time of participation. The Dexcom G4 became unavailable during the course of the study and later participants wore the Dexcom G6. During the first two weeks (Dexcom G4) or first 10 days (Dexcom G6), participants were not able to read the sensor glucose levels. In the second two weeks (Dexcom G4) or second 10 days (Dexcom G6), participants were able to read the sensor glucose levels. Frequency of hypoglycemia was compared between the two phases of the study (masked versus unmasked CGM). Dexcom CGM: The CGM monitored sensor glucose levels in all participants. During the first two weeks (Dexcom G4) or first 10 days (Dexcom G6) of the study, participants were masked to the sensor glucose levels and needed to use other methods, such as a blood sample from a finger stick, to check their blood sugar. During the second two weeks (Dexcom G4) or second10 days (Dexcom G6), participants were able to see the sensor glucose levels displayed from the CGM. Participants were instructed to use this information to treat low glucose levels before symptoms or severely low glucose levels developed.

Total

Withdrawals & dropouts

Period	Reason	FG000
Masked CGM Wear	Lost to Follow-up	2
Unmasked CGM Wear	Excluded due to missing data.	1

Baseline characteristics

Characteristic	CGM Use
Age, Continuous	51.1 years STANDARD_DEVIATION 13
Current BMI	30.6 mg/k^2 STANDARD_DEVIATION 6.1
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	20 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Hemoglobin A1c	5.3 percent STANDARD_DEVIATION 0.4
Percentage of participants with a history of level III hypoglycemia (requiring assistance)	84 percentage of participants
Percentage of participants with a history of neuroglycopenia	100 percentage of participants
Pre-operative Body Mass Index (BMI)	47.6 mg/k^2 STANDARD_DEVIATION 6.4
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	1 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	2 Participants
Race (NIH/OMB) White	22 Participants
Region of Enrollment United States	25 Participants
Sex: Female, Male Female	23 Participants
Sex: Female, Male Male	2 Participants
Visit 1 Dumping Symptom Rating Scale (DSRS) Score	23.1 units on a scale (DSRS score) STANDARD_DEVIATION 7.4
Visit 1 Edinburgh Hypoglycemia Symptom Scale (EHSS) Score	49.3 units on a scale (EHSS score) STANDARD_DEVIATION 20.5
Years between bariatric surgery and hypoglycemia onset	4.7 years STANDARD_DEVIATION 6.3
Years post-bariatric surgery	9.6 years STANDARD_DEVIATION 8.1

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 25	0 / 23
other Total, other adverse events	2 / 25	1 / 23
serious Total, serious adverse events	1 / 25	0 / 23

Outcome results

Primary

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.