Effects of Novel Flash Glucose Monitoring System on Glycemic Control in Adult Patients With Type 1 Diabetes Mellitus

Study Overview
=================
Brief Summary
-----------------
This trial is a randomized, multi-center, parallel-group, efficacy and safety study with a 26-weeks follow- up(after 2-week recruitment). The study aims to: 1)compare the effects of novel flash glucose monitoring system (FGMS) and conventional Self Measurement of Blood Glucose (SMBG); and 2) optimize integrated management for glycaemic control in adult patients with type 1 diabetes who are sub-optimally controlled.

Detailed Description
-----------------
Subjects with Type 1 diabetes who meet criteria will be enrolled at up to eight clinical research sites in China. Subjects will be randomized to either flash glucose monitoring system(Freestyle Libre®;Abbott Diabetes Care,Witney, Oxon,UK) or conventional Self Measurement of Blood Glucose (Bayer®)alone at least three times per day. Primary outcome variable is the difference in HbA1c which will be analyzed in a central laboratory between baseline and the 26weeks follow-up. Secondary outcome variables such as time-in-range, frequency and duration of and hyperglycemic episodes etc. will be assessed at baseline (Week 0 to 2), Week 12-14 and Week 24-26 via professional continuous glucose system (Ipro2®; Medtronic). At the same time, demographic factors, clinical data, patient reported outcome (PROs) will be collected. Assessment of Adverse Events will occur via self-reporting at each visit and/or phone call. All patients will receive same ordinary diabetes education.

Official Title
-----------------
Effects of Novel Flash Glucose Monitoring System on Glycemic Control in Adult Patients With Type 1 Diabetes Mellitus

Conditions
-----------------
Diabetes Mellitus, Type 1

Intervention / Treatment
-----------------
* Device: Flash glucose monitoring system
* Device: SMBG


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Aged 18 years and older; Diagnosed with type 1 diabetes with the criteria established by WHO in 1999,with duration more than 1 year; Glycosylated Hemoglobin A1c concentration between 7% and 10%; Self-monitor of blood glucose levels on a regular basis for 2 months previous( at least 3 times per day) and have willing to insist for at least 6 months Using CSII or MDI for at least 3 months, stable diabetes medication regimen for 3 months prior to study entry(change in insulin ≦20%). Willing to wear CGM; Able to speak, read, and write Chinese Exclusion Criteria: Having used CGM 3 months prior to study entry; Had severe diabetic complications such as PDR in diabetic retinopathy and ESRD of diabetic nephropathy, assessed by investigators; Receiving oral steroid therapy for any disorders and continuous use of paracetamol. Had known allergy to medical-grade adhesives or CGM and its affiliated components; Being pregnant or planning pregnancy (as demonstrated by a positive test at study entry); Recent severe diseases like myocardial infarction,stroke,psychiatric diseases(historical/recent),malignant tumor, kidney disease(defined as eGFR<45), dermatosis, decided by investigator. Current participation in another investigational study (must have completed any previous studies at least 30 days prior to being enrolled in this study); Currently abusing illicit drugs, alcohol, or prescription drugs; Any condition that could impact reliability of the HbA1C measurement,（e.g.hemoglobinopathy, hemolytic anemia, chronic liver disease),decided by investigator.

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Flash Glucose Monitoring System<br>People selected to this group will using flash glucose monitoring system continuously on Week 2-14 and Week 14-26. | Device: Flash glucose monitoring system<br>* Using flash glucose monitoring system continuously on Week 2-14 and Week 14-26<br>* Other names: Freestyle Libre®;Abbott Diabetes Care,Witney, Oxon,UK;|
| Active Comparator: SMBG<br>People selected to this group will using SMBG continuously on Week 2-14 and Week 14-26. | Device: SMBG<br>* Performing SMBG at least three times/day on Week 2-14 and Week 14-26<br>* Other names: Capillary blood glucose tested by Bayer;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycosylated Hemoglobin A1c | Difference in HbA1c at week 14 and week26 adjusted for baseline(week 0) | baseline,week14,week26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time in Range | Difference in time in Range (70-180 mg/dL) assessed in week 12-14 and week 24-26 adjusted for baseline(week 0 to 2) | baseline,week12-14,week24-26 | 
| Time in Hypoglycemia | Difference in time in hypoglycaemia (<70mg/dL,<54mg/dL and<40mg/dL) assessed in week 12-14 and week 24-26 adjusted for baseline(week 0 to 2) | baseline,week12-14,week24-26 | 
| Time in Hyperglycaemia | Difference in time in hyperglycaemia (>180mg/dL and>300mg/dL) assessed in week 12-14 and week 24-26 adjusted for baseline(week 0 to 2) | baseline,week12-14,week24-26 | 
| Percentage of HbA1c in Range | Difference in Percentage of HbA1c at week14 and week 26 adjusted for baseline(week 0) | baseline,week14,week26 | 
| Standard deviation of glucose | Difference in standard deviation of glucose assessed in week 12-14 and week 24-26 adjusted for baseline(week 0 to 2) | baseline,week12-14,week24-26 | 
| Mean glucose levels | Difference in mean glucose levels assessed in week 12-14 and week 24-26 adjusted for baseline(week0 to 2) | baseline,week12-14,week24-26 | 
| The area under the curve of hypoglycemia/ hyperglycaemia |  | baseline,week12-14,week24-26 | 
| Frequency in hypoglycemia/ hyperglycaemia |  | baseline,week12-14,week24-26 | 
| Frequency in severe hypoglycaemia |  | baseline,week12-14,week24-26 | 
| Frequency in adverse events about device |  | 26weeks | 
| Frequency in using FGM |  | 24 weeks | 
| Frequency in SMBG |  | 26 weeks | 
| Total daily dose of insulin |  | 26 weeks | 
| The Diabetes Distress Scale (DDS) | The Chinese version of the Diabetes Distress Scale is to evaluate diabetes-related emotional distress in Chinses diabetic patients. The scale consists of 17 items, contains four domains including emotional burden sub-scale, physician-related distress subscale, regimen-related distress subscale, and diabetes-related interpersonal distress. Each item is rated on a 6-point Likert scale from 1(no problem) to 6(serious problem). An average score ≥3 is the cut-off point which is considered to more than moderate problem. Administration time is approximately 10 minutes. | baseline,week 14 and week 26 | 
| Hypoglycaemia Fear Scale(HFS) | The Chinses version of Hypoglycemia Fear Survey II- Worry Scale (CHFSII-WS) is to evaluate psychological status for diabetic patients. Change in Hypoglycemia Fear Scale (HFS) score will be assessed in week 14 and week 26 adjusted for baseline(week0). These validated surveys consist of 18 questions which measure dimensions of anxiety and fear surrounding hypoglycemia. Each item is rated on 5-point Likert scale from 0(never related) to 4(very related). Never relative scores 1, and so on and so forth, and very related scores 4. Patients with higher scores are considered with more anxieties and fear of hypoglycemia. Administration time is approximately 10 minutes. | baseline,week 14 and week 26 | 
| EQ-5D-5L | The Chinese version of the EQ-5D-5L is widely used to evaluate quality of life. The EQ-5D-5L is converted to a single summary index by applying a formula that essentially attaches weights to each of the levels in each dimension. The formula is based on the valuation of EQ-5D health states from general population samples. It contains the health description system and Visual Analogue Score (VAS). The health description system includes 5 dimensions including mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each item is rated on 5 levels from 1(no problems) to 5(extreme problem). And the EQ-VAS is to evaluate the health condition assessed by patients. The top score (100) means the best health conditions and the bottom one (0) means the worst. Administration time is approximately 3minutes. Difference in EQ-5D-5Ls assessed in week 14 and week26 adjusted for baseline(week0-2). | baseline,week 14 and week 26 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
FGMS, Flash glucose monitoring system