Long-Term Feedback Effect of FGM in Newly-Diagnosed T2D Patients

Study Overview
=================
Brief Summary
-----------------
This clinical trial aims to evaluate the educational training of 12-weeks using flash glucose monitoring (FGM) FreeStyle Libre2 (FSL2; Abbott Diabetes Care Inc., Alameda, CA, USA) in newly- diagnosed T2D subjects who are treated with metformin in term of sustained improvement in glycemic variability (TIR) after the discontinuation of FGM compared to self-monitoring of blood glucose (SMBG). This clinical trial also aim to explore which frequency of sensor wear at the diagnosis is more effective in achieving a sustained improvement in TIR after the FGM discontinuation over time.

Detailed Description
-----------------
Diabetes self-management represents the cornerstone of successful and cost-effective diabetes care, reducing the occurrence of complications, hospital admissions and readmission as well as estimated lifetime health care costs related to a lower risk for complications. Recent advances in diabetic technology may help to address some of these issues : Flash glucose monitoring (FGM) is a novel system of interstitial glucose monitoring intended to replace the capillary blood glucose measurement which proved to ameliorate glycemic variability and quality of life, beyond the good precision, increased time in range, and ease of wear. However, FGM is not currently used as an educational tool in patients with newly diagnosis of T2D who are not on insulin therapy. Therefore, the rationale for this three-armed parallel group randomized controlled trial is that the continuous flow of data from FGM and the visual display of moment-to-moment glucose levels as a trend could provide real-time feedback also in newly T2D patients, assessing which frequency of sensor is superior in enhancing mindfulness and in ameliorating of glycemic control ,quality of life and well-being perception. The entire study participation will span approximately 6 months and will be performed in the facilities of Fondazione Policlinico Campus Bio-Medico University of Rome enrolling 42 participants. The intervention phase will last 12 weeks followed by more 12 weeks in the follow-up phase. Each participant will have a screening visit ( week -4), a baseline visit ( week -2), a randomization visit (week 0) and three follow up visits at week 12 and 23 and 24 for all the groups. Every group will wear also a blinded device (Free Style Libre Pro IQ) for registration of glicemyc variability at the baseline visit and a the end of the study ; group 1 will wear it also between intervention and follow-up phase ( weeks 11-12). All patients will be asked to fill out a food diary at both the intervention and follow-up phases. A high glycemic index meal will also be administered during the randomization visit ( week 0) in order to record the emotional state of study subjects in response to postprandial glycemic values. Randomization will be performed following a ratio equal to 1:1:1 and blocked for gender. The primary outcome of the study is the difference in the means of time in range (TIR) at weeks 23-24 adjusted for baseline phase values. Secondary endpoints include the difference in TIR assessed at weeks 11-12 among the three groups and within the three groups as well as difference in A1c, HOMA IR, weight, body composition and oxidative stress among the groups. Quality of life/well-being perception/mindfulness will be investigated at week 0, week 12 and week 24 through several questionnaires.

Official Title
-----------------
Long-Term Feedback Effect of Flash Glucose Monitoring (Freestyle Libre2®) in Newly-Diagnosed Type 2 Diabetic Patients: a Randomized Monocentric Parallel-group Clinical Trial

Conditions
-----------------
Type 2 Diabetes

Intervention / Treatment
-----------------
* Device: flash glucose monitoring continuous
* Diagnostic Test: capillary blood test
* Device: flash glucose monitoring intermittent


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosed with type 2 diabetes mellitus ( according to the ADA Guidelines ) within the past 12 months Must be taking only metformin as glucose lowering treatments, Older than 18 years, Body Mass Index equal or greater than 25 Kg/m^2, Must be able to provide written informed consent . Exclusion Criteria: diagnosis of type 1 diabetes; glycated hemoglobin exceeding 8.5% alcohol or drug abuse/dependency antidiabetic therapy other than metformin; pregnancy (on-going or planned during the study); severe illness (physical or mental health); cognitive impairment; high dose steroids; hospitalized more than 2 times in past 12 months previous bariatric intervention or gastrectomy; pace maker use uncorrected vision impairment; already using a continuous glucose monitor or flash glucose monitor; any allergy to the component of the device.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: three-armed parallel group
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: group 2 - FGM continuous<br>Patients will be asked to wear the sensor FreeStyle Libre2 continuously | Device: flash glucose monitoring continuous<br>* Group 2 (FGM continuous): will be asked to wear the sensor FreeStyle Libre2 for the FGM with the following frequency fashion continuously for the first 12 weeks and followed by 12 weeks testing as recommended by their usual provider.<br>|
| Experimental: group 3 - FGM intermittent<br>will be asked to wear the sensor FreeStyle Libre2 intermittently | Device: flash glucose monitoring intermittent<br>* Group 3 (FGM intermittent): will be asked to wear the sensor FreeStyle Libre2 for the FGM with the following frequency fashion 1 week off/2 weeks on for the first 12 weeks and followed by 12 weeks testing as recommended by their usual provider.<br>|
| Active Comparator: group 1- SMBG<br>Patients will be asked to test capillary blood glucose as recommended by subjects' usual provider | Diagnostic Test: capillary blood test<br>* Group 1 (SMBG): will be asked to test capillary blood glucose as recommended by subjects' usual provider for the first 12 weeks and followed by 12 weeks testing as recommended by their usual provider.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time in range | difference in the means of time in range (TIR) registered at the weeks 23-24 phase through blinded device Free style Libre PRO-IQ, among the three groups and adjusted for baseline phase values. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time in range | difference in the means of time in range (TIR) assessed at weeks 11-12 among the three groups,and adjusted for baseline phase values | 3 months | 
| mindfulness | changes in eating mindfulness questionnaire score ( 28 items, each questions from 0 to 4 points) evaluated among the three groups and adjusted for baseline values. Higher scores on the mindful eating questionnaire overal, and on each of the categories ( Awareness , Distraction,Disinhibition,Emotional Response, External Cues)-has been associated with a lower body mass index and long-term weight maintenance | 3-6 months | 
| Body Mass Index (BMI,kg/m^2) | changes in body mass (Kg) divided by the square of the body height (m), and is expressed in units of kg/m^2, resulting from mass in kilograms (kg) and height in metres (m) at weeks 12 and 24. | 6 months | 
| Body Composition | changes in fat mass ( Kg ) and Fat free mass (Kg) assessed with bioelectrical Impedance Analysis adjusted for baseline values. | 6 months | 
| Physical activity | evaluation of the types of intensity of physical activity in the previous 7 days assessed by th International Physical Activity Questionnaire ( IPAQ)- short form at week 24 among the three groups. Total physical activity will be expressed in MET ( Metabolic Equivalent of Task)-min/week and time spent sitting . MET< 700 is indicative of inactive person, MET above 2520 is indicative of very active person | 6 months | 
| d-ROMs derivatives-reactive oxygen metabolites | changes in derivatives-reactive oxygen metabolites (d-ROMs, U.Carr) after the discontinuation of FGM compared with SMBG | 3-6 months | 
| PAT plasma antioxidant capacity | changes in plasma antioxidant capacity ( PAT test, μmol/L ) after the discontinuation of FGM compared with SMBG | 3-6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
time in range, quality of life, bio feedback, flash glucose monitoring