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

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Glucose
• Intervention / Treatment: Device: FreeStyle Libre Flash Glucose Monitor; Other: Diabetes self-management education

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 116
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Brampton, Ontario, Canada, L6S 0C6
      • LMC Brampton
    • Etobicoke, Ontario, Canada, M9R 4E1
      • LMC Etobicoke
    • Oakville, Ontario, Canada, L6M 1M1
      • LMC Oakville
    • Ottawa, Ontario, Canada, K2J 0V2
      • LMC Ottawa
    • Toronto, Ontario, Canada, M4G 3E8
      • LMC Midtown
    • Vaughan, Ontario, Canada, L4K 4M2
      • LMC Vaughan/Thornhill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention (FGM + DSME); 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; 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.; Other: Diabetes self-management education; 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.
Other: Control (DSME alone); 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; 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory analysis 1a: Glucose control - Targeted glucose range	Within group change in the proportion of time spent in targeted glucose range based on FGM metrics from the first 2-week and final 2-week periods of Phase 2	16-week period
Exploratory analysis 1b: Glucose control - hypoglycemia	Within group change in the proportion of time spent in hypoglycemia (<3.8 mmol/L) ranged based on FGM metrics from the first 2-week and the final 2-week periods of Phase 2	16-week period
Exploratory analysis 1c: Glucose control - hyperglycemia	Within group change in the proportion of time spent in hyperglycemia (>10 mmol/L) range based on FGM metrics from the first 2-weeks and final 2-week periods of Phase 2	16-week period
Exploratory analysis 1d: Glucose control - HbA1c	Within group change in HbA1c based on blood drawn for laboratory testing from the first 2-week and the final 2-week periods of Phase 2	16-week period
Exploratory analysis 1e: Glucose control - Mean glucose	Within group change in mean glucose based on FGM metrics from the first 2-week and final 2-week periods of Phase 2	16-week period
Exploratory analysis 1f: Glucose control - Glycemic variability	Within group change in standard deviation and % coefficient of variation based on FGM metrics from the first 2-week and final 2-week periods of Phase 2	16-week period
Exploratory analysis 1g: Glucose control - Hypoglycemia	Within group change in the frequency of hypoglycemia based on FGM metrics from the first 2-week and final 2-week periods of Phase 2	16-week period
Exploratory analysis 1h: Glucose control - Severe hypoglycemia	Within group change in the frequency of severe hypoglycemia, defined as a hypoglycemic episode that required assistance of another person to actively administer carbohydrate, glucagon or other resuscitative actions, based on FGM metrics from the first 2-week and final 2-week periods of Phase 2	16-week period
Exploratory analysis 2a: Patient reported outcome - Adherence	Within group change in the Adherence to Refills and Medication-Diabetes (ARMS-D) from the beginning to the end of Phase 2	16-week period
Exploratory analysis 2b: Patient reported outcome - Psychological distress	Within group change in the Diabetes Distress Scale from the beginning to the end of Phase 2.	16-week period
Exploratory analysis 2c: Patient reported outcome - Device satisfaction	Within group change in the Glucose Monitoring System Satisfaction Survey from the	16-week period
Exploratory analysis 2d: Patient reported outcome - Participant self-efficacy	Within group change in the Skills, Confidence and Preparedness Index (SCPI) from the beginning to the end of Phase 2.	16-week period
Exploratory analysis 3a: Effect of DSME goal achievement	The effect of DSME goal achievement, independent of glucose monitoring system used, on the change in proportion of time spent in targeted glucose range in the final 2-week CGM period of Phase 1 vs baseline	16-week period
Exploratory analysis 3b: Effect of DSME goal achievement	The effect of DSME goal achievement, independent of glucose monitoring system used, on the frequency of FGM-measured hypoglycemia in the final 2-week CGM period of Phase 1 vs baseline	16-week period
Exploratory analysis 3c: Effect of DSME goal achievement	The effect of DSME goal achievement, independent of glucose monitoring system used, on the association between the daily frequency of FGM scanning/self-monitored blood glucose and TIR.	16-week period
Exploratory analysis 4: Frequency of glucose testing	The optimal frequency of glucose testing for greatest impact on glycemic control (TIR)	16-week period

Collaborators and Investigators

• Sponsor: LMC Diabetes & Endocrinology Ltd.
• Collaborators: Abbott Diabetes Care
• Investigators: Principal Investigator: Ronnie Aronson, MD, LMC Diabetes

Publications and helpful links

General Publications

• Polonsky WH, Fisher L, Earles J, Dudl RJ, Lees J, Mullan J, Jackson RA. Assessing psychosocial distress in diabetes: development of the diabetes distress scale. Diabetes Care. 2005 Mar;28(3):626-31. doi: 10.2337/diacare.28.3.626.
• Mayberry LS, Gonzalez JS, Wallston KA, Kripalani S, Osborn CY. The ARMS-D out performs the SDSCA, but both are reliable, valid, and predict glycemic control. Diabetes Res Clin Pract. 2013 Nov;102(2):96-104. doi: 10.1016/j.diabres.2013.09.010. Epub 2013 Sep 26.
• Polonsky WH, Fisher L, Hessler D, Edelman SV. Development of a New Measure for Assessing Glucose Monitoring Device-Related Treatment Satisfaction and Quality of Life. Diabetes Technol Ther. 2015 Sep;17(9):657-63. doi: 10.1089/dia.2014.0417. Epub 2015 Apr 29.
• Aronson R, Li A, Brown RE, Walker A, Lyons A, Orzech N. Optimizing Diabetes Self-management Using the Novel Skills, Confidence, and Preparedness Index (SCPI). Diabetes Care. 2019 Oct;42(10):1873-1878. doi: 10.2337/dc19-0699. Epub 2019 Aug 9.

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2020
• Primary Completion (Actual): September 6, 2022
• Study Completion (Actual): September 6, 2022

Study Registration Dates

• First Submitted: September 1, 2020
• First Submitted That Met QC Criteria: September 18, 2020
• First Posted (Actual): September 24, 2020

Study Record Updates

• Last Update Posted (Estimated): November 8, 2023
• Last Update Submitted That Met QC Criteria: November 6, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Randomized controlled trial; Type 2 diabetes; Glucose monitoring; Flash sensor glucose technology
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: IMMEDIATE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes