Clinical trial NCT04147637: FreeStyle Libre Plus Bluetooth Transmitter Adjunct: Can This Improve Glucose Accuracy and Reduce Burden of Hypoglycaemia
Official title: Crossover Randomized Controlled Trial of FreeStyle Libre Plus Bluetooth Transmitter Compared to FreeStyle Libre Alone in People With Type 1 Diabetes Mellitus. Can This Improve Accuracy and Reduce Burden of Hypoglycaemia
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Type1 Diabetes Mellitus
Keywords: Hytpoglycemia
FreeStyle Libre
Flash Glucose Monitoring
MiaoMiao
Time in Range
Lead sponsor: Dasman Diabetes Institute
Sponsor class: OTHER
First posted: 2019-11-01
Enrollment: 0
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Randomized crossover study
Primary purpose: SUPPORTIVE_CARE

Brief summary: Advanced glucose monitoring systems have revolutionized diabetes care and enabled people with diabetes to achieve better diabetes control with reduced risk of hypoglycaemia. Continuous glucose monitoring (CGM) systems provide real-time glucose monitoring and alarms when glucose approaches extreme readings (hypoglycaemia and hyperglycaemia) or when the change in glucose is rapid. All available CGM systems, except Dexcom G6, require daily calibrations with capillary glucose readings in order to attain accuracy of glucose readings. Decom G6 system is not widely accessible and only available in certain countries. Flash glucose monitoring systems (Flash) provide glucose readings when users actively scan their sensors. FreeStyle Libre (FSL) is the only Flash glucose monitoring system currently available in market. FSL is factory calibrated and sensors are ready to use after placement and initiation. The two main differences between Flash and CGM are user interaction and the alarm facility. While CGM provide real-time glucose readings, Flash is user-dependent for actively scanning and understanding the readings. Moreover, CGM systems provide alarms for low or high glucose and for rapid glucose changes, while Flash does not routinely provide alarms. This is particularly relevant when patients have impaired or lost hypoglycaemia awareness. CGM systems are costlier compared to Flash, which has contributed to the wider adoption of FSL.

Several Bluetooth adjuncts have been introduced to market for FSL. These devices attach to Libre sensor and connect to the user's mobile phone via Bluetooth. This enables continuous and real-time feed of glucose readings from the sensor to patient's mobile phone, which enables a wide range of customizable alarms for high and low glucose levels and for rapid glucose changes. This setup also enables calibration of Libre sensor with capillary glucose which, anecdotally, has been reported to improve sensor accuracy. None of these adjuncts have been validated clinically. FSL with Bluetooth adjunct such as MiaoMiao remain cheaper than current CGM options and could be more accessible in some countries than CGM. However, without robust evidence to support effectiveness and safety of such setup it is not possible to recommend this.

The Objective of this study is to determine whether FSL with Bluetooth Adjunct is superior to FSL alone in accuracy and reduction of hypoglycaemia burden.

Detailed description: Study design:

Open-label, crossover, single center, randomized controlled trial of FreeStyle Libre with MiaoMiao Bluetooth transmitter adjunct with calibrations (FSL-M) compared to FreeStyle Libre alone (FSL-A) in people with T1DM.

Protocol summary:

Following informed written consent, subjects will be randomized to either FSL-M group using FSL with Miaomio and Tomato App premium version, or FSL-A with Libre Link app (stage 1). Subjects will spend 8 weeks in the assigned group followed by 2 weeks washout then subjects will switch over to the other group for further 8 weeks (stage 2).

While in FSL-M, subjects will be asked to calibrate FSL with daily capillary glucose values using Contour Plus, or on days 1, 2, 4, 8, 13 of sensor life. Alarms for low glucose (\<3.9mmol/L, \<70mg/dL) and high glucose (\>13.9mmol/L, 250mg/dL) will be set in Tomato App.

7-point capillary glucose profiles will be carried out by subjects in both groups on days 2/3, 5/6, 9/10, 13/14 of each sensor life to enable paired comparison with sensor values.

Subjects will have routine labs at randomization, end of stage 1, and end of stage 2. All subjects will be asked to complete the following questionnaires: GOLD, Problem Areas in Diabetes (PAID) and Diabetes Quality of Life (DQOL) at randomization, at end of stage1 and end of stage 2. The group randomized to FSL-M at stage 1 will have qualitative interview at randomization, end of stage 1 and end of stage 2.

All adverse events will be collected including, but not limited to, all hypoglycaemia, diabetic ketoacidosis, hospital admissions for any reason, and device related skin reaction for the duration of the study in all subjects in both groups.

Data analysis will be carried out on glucose data retrieved from Libre view web-platform and Tomato App downloads in addition to Contour Plus meter downloads.

Eligibility criteria: Inclusion Criteria:

1. T1DM for 12 months or more
2. Age \>21 years old
3. Established user of FreeStyle Libre for ≥3 months
4. HbA1C \<12% (108mmol/mol)
5. Able to check glucose with finger prick several times a day

Exclusion Criteria:

1. Pregnancy or plans for pregnancy over the duration of the study
2. Breast feeding
3. Renal impairment with eGFR \<30ml/minute/1.73m2
4. Significant anaemia (males Hb\<110g/L, females Hb \<100g/L)
5. Active malignancy
6. Significant vision impairment
7. Any significant illness- decision will be made by the PI or Co-I
8. Not able to attend study visits
9. Not able or not willing to participate in all study components
10. Not able or not willing to give written informed consent

Primary outcomes:
measure: Mean absolute relative difference (MARD)
timeFrame: 9 months
measure: Percentage time below 3.0mmol/L (54mg/dL)
timeFrame: 9 months
measure: Percentage time in range 4-10mmol/L
timeFrame: 9 months
Secondary outcomes:
measure: Percentage time <4mmol/L (72mg/dL)
timeFrame: 9 months
measure: Percentage time >10mmol/L
timeFrame: 9 months
measure: Change in HbA1C
timeFrame: 9 months
measure: Rate of hypoglycaemia
timeFrame: 9 months
measure: Rate of severe hypoglycaemia
timeFrame: 9 months
measure: Rate of device-related complications
timeFrame: 9 months
measure: Change in dose of insulin
timeFrame: 9 months
Other outcomes:
Locations:
city: Kuwait City
country: Kuwait
facility: Ali Aldibbiat
Study officials:
affiliation: Dasman Diabetes Institute
name: Ali Aldibbiat, MD PhD FRCP
role: PRINCIPAL_INVESTIGATOR
References: