Impact of Flash Glucose Monitoring in People With Type 2 Diabetes Using Non-Insulin Antihyperglycemic Therapy

Study Overview
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Brief Summary
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The objective of this study is to evaluate the effectiveness of a flash glucose monitor device in achieving optimal glycemic control among adults with type 2 diabetes inadequately controlled with non-insulin antihyperglycemic therapy.

Detailed Description
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The IMMEDIATE study is a multi-centre, randomized controlled, open-label, two-phase cross-over study evaluating the effectiveness of a flash glucose monitor device to increase the proportion of time spent in target glucose range (3.9 to 10.0 mmol/L) among adults with type 2 diabetes inadequately controlled with non-insulin antihyperglycemic therapy compared to a control group not using a flash glucose monitor device. The study will consist of two phases; each 16 weeks long. In Phase 1, study participants who meet eligibility criteria will be randomized to receive a flash glucose monitor device combined with diabetes self-management education, or diabetes self-management education alone. In Phase 2, participants initially assigned to receive education alone will crossover to receive a flash glucose monitor device while participants initially using the flash glucose monitor will continue using their device. No diabetes self-management education will be provided during Phase 2.

Official Title
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IMpact of Flash Glucose Monitoring in pEople With Type 2 Diabetes Inadequately Controlled With Non-insulin Antihyperglycemic ThErapy - IMMEDIATE Study

Conditions
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Diabetes Mellitus, Type 2, Glucose

Intervention / Treatment
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* Device: FreeStyle Libre Flash Glucose Monitor
* Other: Diabetes self-management education


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible participants must be an adult aged 18 years or older and: A clinical diagnosis of T2D, with diagnosis known for six months or more; An HbA1c of > 7.5%; Using one or more non-insulin antihyperglycemic therapy for a minimum of six months, with dose stability of 3 months; and No previous history of using CGM or FGM devices. Exclusion Criteria: Participants will be excluded from the study if they: Have a history of insulin use > 3 months Are pregnant or breastfeeding Have diabetic retinopathy Have an estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73 m2 Have unstable cardiovascular disease Use other implanted medical devices, such as pacemakers Have had more than one episode of severe hypoglycemia during the past 6 months or evidence of hypoglycemia unawareness Anticipate or require regular magnetic resonance imaging, computed tomography scan, or high-frequency electrical heat (diathermy) treatment

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The IMMEDIATE study is a two-phased, cross-over study. In Phase 1, participants will be randomized at a 1:1 ratio, stratified by use of glucagon-like peptide-1 receptor agonist to receive either a flash glucose monitor (FGM) + diabetes self-management education (DSME) (Intervention arm) or to DSME alone (Control arm). Participants randomized to the Intervention arm will receive a FreeStyle Libre FGM System, 1 training session on its proper use, and 6 DSME sessions. Participants randomized to the Control arm will receive 6 DSME sessions matched to time and location of the Intervention group. DSME sessions for both groups will consist of four individual in-clinic sessions and two telephone sessions. After 16-weeks, participants initially assigned to DSME alone will cross-over to receive the intervention FGM device, while those initially randomized to using a FGM will continue using their device for an additional 16 weeks (Phase 2). No DSME will provided during Phase 2.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention (FGM + DSME)<br>Study participants randomized to the intervention arm will be provided with a FreeStyle Libre flash glucose monitor (FGM) system to use for 16 weeks in Phase 1. Study participants will receive one training session on proper use of the FGM and encouraged to test at least 4 times per day: fasting and post-meals. Participants will also receive six diabetes self-management education (DSME) sessions, consisting of four individual in-clinic sessions and two telephone sessions. | Device: FreeStyle Libre Flash Glucose Monitor<br>* The FreeStyle Libre FGM device consists of a skin-worn disposable sensor that automatically measures and continuously stores glucose readings. The sensor is placed by a single-use applicator and is activated by a wireless scan with a handheld reader. It is designed to stay on the body for up to 14 days, and can be worn under clothing. After a 1-hour warm-up period, the sensor takes automatic measurements of glucose every 15 minutes for up to 14 days. The device collects the interstitial glucose values and stores them for subsequent upload at the end of the 14-day wear period. With each scan, users receive their glucose reading; the last eight hours of glucose data; and an arrow illustrating the direction their glucose is heading.<br>Other: Diabetes self-management education<br>* The DSME curriculum is compromised of: Review of weekly glucose report (Trend glucose report from Libreview for intervention group; and weekly glucose report in log book format from their glucose monitoring software for control group) Education modules for both in-person and remote delivery; Handouts to support the curriculum objectives; and Blood glucose monitoring challenges to stimulate behaviour change and reinforce learning.<br>|
| Other: Control (DSME alone)<br>Study participants in the control arm will receive six diabetes self-management education sessions matched to time and location of the intervention group. The sessions will consist of four individual in-clinic sessions and two telephone sessions over 16 weeks. Control participants will be encouraged to self-monitor blood glucose four times daily (fasting and post-meals) as per existing diabetes self-care guidelines | Other: Diabetes self-management education<br>* The DSME curriculum is compromised of: Review of weekly glucose report (Trend glucose report from Libreview for intervention group; and weekly glucose report in log book format from their glucose monitoring software for control group) Education modules for both in-person and remote delivery; Handouts to support the curriculum objectives; and Blood glucose monitoring challenges to stimulate behaviour change and reinforce learning.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time in Range (TIR) | The proportion of time within target glucose range (3.9 to 10.0 mmol/L) among adults with type 2 diabetes (T2D) inadequately controlled with non-insulin antihyperglycemic therapy compared to a control group not using an FGM device measured during the blinded continuous glucose monitor (CGM) period during the final last two-weeks of the Phase 1 | 2-week period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycemic control (a) | Mean HbA1c (blood drawn for laboratory testing) at the end of Phase 1 | 2-week period | 
| Glycemic control (b) | Proportion of participants with HbA1c < 7.0% and with HbA1c > 9.0% at the end of Phase 1 | 2-week period | 
| Glycemic control (c) | Mean glucose based on blinded CGM recordings at the end of Phase 1 | 2-week period | 
| Proportion of time spent in various glycemic ranges based on blinded CGM recordings | Tight glycemic range (3.9 to 7.8 mmol/L) Hypoglycemia range (3.0 to 3.8 mmol/L) Clinically significant (level 2) hypoglycemia range (< 3.0 mmol/L) Hyperglycemia (> 10.0 mmol/L) | 2-week period | 
| Glycemic variability | Standard deviation and % coefficient of variation based on blinded CGM recordings | 2-week period | 
| Number of documented episodes of hypoglycemia episodes | Based on the blinded CGM recording, including: All (hypoglycemic episode occurring at anytime); Nocturnal (hypoglycemic episode occurring between 12 am and 6 am); and Level 2 hypoglycemic (<3.9 mmol/L) | 2-week period | 
| Number of episodes of severe hypoglycemia | A hypoglycemic episode that requires assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions as reported by participant | 16-week period | 
| Adherence to diabetes medications as measured by the Adherence to Refills and Medication-Diabetes (ARMS-D) | The ARMS-D is an 11-item self-reported measure of adherence that assesses one's ability to take and refill medication under different circumstances, and identifies barriers to medication adherence. The ARMS-D demonstrates good internal consistency, reliability (α=0.86), shows good convergent validity with other adherence to medication scales, and independently predicts HbA1c (β=0.16, p<0.01) | 2-week period | 
| Psychological distress as measured by the Diabetes Distress Scale (DDS) | The DDS is a 17-item scale that captures four dimensions of distress: emotional burden, regime distress, interpersonal distress and physician distress. The DDS list potential problem areas that people with diabetes may experience. Respondents are asked to indicate the degree to which each problem may be bothering them in their life on a 6-point Likert Scale from 1 (not a problem) to 6 (a very serious problem). The DDS and its subscales has been shown to have good internal reliability (α > 0.87) and validity. | 2-week period | 
| Device satisfaction as measured by the Glucose Monitoring System Satisfaction Survey (GMSS) | The GMSS is a 15-item self-reported measure of glucose device satisfaction. The GMSS provides a comprehensive profile of key contributors to device satisfaction. The GMSS has shown good criterion validity against the World Health Organization-5 measure of quality of life and the DDS, and the Self-Monitoring Blood Glucose (SMBG) Obstacles scale (all p < 0.001) | 2-week period | 
| Participant self-efficacy as measured by the Skills, Confidence and Preparedness Index (SCPI) | The SCPI is a 23-item scale that includes three subscales: Skills; confidence; and preparedness. Each question contains a 7-point Likert scale response. The SCPI has been demonstrated to have high validity internal consistency and test-retest reliability, with no floor or ceiling effect. Furthermore, SCPI scores are significantly correlated with HbA1c in both type 1 diabetes and T2D populations (p < 0.001) | 2-week period | 
| Change in antihyperglycemic therapies | Change in the mean number of antihyperglycemic therapies from baseline to end of | 2-week period | 
| Change in weight (kg) | Change in weight (kg) from baseline to end of Phase 1 | 16-week period | 
| Change in waist circumference (cm) | Change in waist circumference (cm) from baseline to end of Phase 1 | 16-week period | 
| Diabetes self-management education (DSME) goals setting | Mean number of diabetes self-management education (DSME) goals set per person | 16-week period | 
| Mean DSME goal achievement score during Phase 1 | Each DSME goal set during the trial is be graded on a 6-point rating scale. Goal attainment scores range from 1 (goal not attempted) to 6 (exceeded expectation). | 16-week period | 
| Mean number of glucose checks | Mean number of FGM scans for the intervention group; and mean number of self-monitoring of blood glucose for the control arm | 2-week period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glucose monitoring, Randomized controlled trial, Type 2 diabetes, Flash sensor glucose technology