ACCU-CHEK® Aviva Expert Study: Does Use of a Bolus Advisor Improve Glycemic Control in Patients Not Achieving Optimal Control Using Multiple Daily Injections (MDI)?

Study Overview
=================
Brief Summary
-----------------
This clinical, prospective, randomized, multi-center study determined if the use of an insulin bolus advisor improves glycemic control as measured by a change in HbA1c in patients failing multiple daily injection/intensified conventional therapy (MDI/ICT).

Detailed Description
-----------------
Eligible participants were randomized to 24 weeks multiple daily injection therapy using either the Accu-Chek® Aviva Expert blood glucose meter with an integrated bolus advisor or the Accu-Chek® Aviva Nano blood glucose meter and manual bolus calculation.

Official Title
-----------------
A Prospective, Multi-centre Study With Diabetic Patients Randomized to 24 Weeks Treatment Supported by Either Accu-Chek® Aviva Expert Blood Glucose Meter With an Integrated Bolus Advisor or MDI Standard Therapy With Accu-Chek® Aviva Nano Meter (Without Bolus Advisor)

Conditions
-----------------
Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2

Intervention / Treatment
-----------------
* Device: Aviva Expert blood glucose meter
* Device: Aviva Nano blood glucose meter


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Must be 18 years of age or older. Diagnosed with Type 1 or Type 2 diabetes. Recent HbA1c > 7.5% (measured within the last 6 weeks at local laboratory). On multiple daily injection (MDI) therapy for at least 6 months consisting of 1-2 injections per day of long-acting basal insulin (Lantus® or Detemir®) and at least 2 injections per day of regular or rapid-acting analog insulin for meal coverage. Subject adjusts meal insulin doses based on carbohydrate content of meals. Subject with Type 2 diabetes may be on stable metformin therapy (therapy unchanged during 3 months prior to study). Subject has been in Investigator's practice for at least 3 months but may have been seen by another physician in the practice. Subject has completed carbohydrate (CHO) training within the last 2 years. Exclusion Criteria: Subject is on a therapy regimen that conflicts with the study: Neutral protamine Hagedorn (NPH) or pre-mixed insulin; oral anti-diabetic agents, with the exception of metformin; injectable anti-diabetic agents other than long-acting insulin and rapid-acting insulin analogs or regular insulin (eg, fixed dose therapy); use of sliding scale insulin therapy that determines insulin dosages based exclusively on specific blood glucose (bG) results. Subject has participated in another interventional trial within 6 weeks prior to study. Subject has been diagnosed with any clinically significant infectious disease or major organ system disease, such as gastroparesis or renal disease (at Investigator's discretion). Subject has used systemic oral or inhaled steroids for more than 7 days within the last 3 months. Subject is on chemotherapy or radiation therapy (self-reported). Subject is pregnant or lactating or is currently planning a pregnancy.

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: Diagnostic
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aviva Expert blood glucose meter<br>Participants used the Accu-Chek® Aviva Expert blood glucose meter with an integrated bolus advisor to determine the dose of insulin for each injection in their 24 week multiple daily injection therapy. | Device: Aviva Expert blood glucose meter<br> <br> |
| Active Comparator: Aviva Nano blood glucose meter<br>Participants used the Accu-Chek® Aviva Nano blood glucose meter and manual bolus calculation to determine the dose of insulin for each injection in their 24 week multiple daily injection therapy. | Device: Aviva Nano blood glucose meter<br> <br> |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Glycosylated Hemoglobin A1c (HbA1c) From Baseline to Week 24 | HbA1C was measured in blood samples at a central laboratory. | Baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Blood Glucose Measurements Within the Blood Glucose Target Range From Screening to Baseline and From Week 23 to Week 24 | Participants measured their blood glucose at least 3-4 times daily throughout the study. The mean blood glucose level was calculated for each 3-day period from Baseline to Week 24 and the percentage of 3-day blood glucose levels with the target range of 70-180 mg/dL (3.9-10 mmol/L) was calculated for the 2 reporting periods of Screening to Baseline and Week 23 to Week 24. | Screening to Week 24 | 
| Number of Symptomatic Hypoglycemic Episodes Per Subject Year From Screening to Baseline and From Week 23 to Week 24 | A symptomatic hypoglycemic episode was defined as an event with symptoms consistent with hypoglycemia which was confirmed by a blood glucose reading < 70 mg/dL (3.9 mmol/L). Symptoms might include but were not limited to sweating, dizziness, lightheadedness, tremors, nervousness, hunger, headaches, and weakness or tiredness. | Screening to Week 24 | 
| Change in the Mean Amplitude of Glucose Excursion (MAGE) From Baseline to Week 24 | Approximately half of the investigational sites monitored glucose levels in participants enrolled in this study using the DexCom Seven® Plus Continuous Glucose Monitoring device. The device provides glucose measurements every 5 minutes for up to 7 days. The system contains a sensor, transmitter, and receiver. The sensor is a flexible round wire that goes under the skin to read glucose levels. The transmitter snaps into the sensor and wirelessly sends glucose readings to the receiver. Data was obtained from approximately one-third of participants and was used to calculate MAGE. Data were collected in the 3 days prior to Baseline and the Week 24 visit. The standard deviation of the blood glucose measurements in each 3-day period was calculated. For each glucose measurement, the difference from the previous reading was calculated. Absolute differences smaller than the standard deviation were discarded. MAGE is the mean of the remaining difference scores. | 3 days prior to Baseline to Week 24 | 
| Percentage of Bolus Opportunities Where the Accu-Chek® Aviva Expert Blood Glucose Meter Bolus Advisor Was Used During the Study | Participants using the Accu-Chek® Aviva Expert blood glucose meter were encouraged to use the Bolus Advisor utility incorporated into the meter. A bolus opportunity occurs, for example, just before eating a meal. | Baseline to Week 24 | 
| Number of Accu-Chek® Aviva Expert Blood Glucose Meter Bolus Advices Modified Per Day by Participants During the Study | Participants using the Accu-Chek® Aviva Expert blood glucose meter were encouraged to use the Bolus Advisor utility incorporated into the meter. A bolus opportunity occurs, for example, just before eating a meal. | Baseline to Week 24 | 
| Correct and Incorrect Use of Insulin:Carbohydrate Ratio (I:CHO) and Insulin Sensitivity Factor (ISF) Advice by Participants Using the Aviva Nano Blood Glucose Meter During the Study | Participants using the Aviva Nano blood glucose meter received individualized advice in how to use their insulin:carbohydrate ratio (I:CHO) and insulin sensitivity factor (ISF) values to determine their insulin dose. The I:CHO ratio advice was considered to have been used correctly if the meal bolus dose the participant indicated in his/her patient diary was in accordance with the dose which could be calculated based upon the participant's total carbohydrate intake and the I:CHO ratio. The ISF advice was considered to have been correctly used if the correction bolus dose the participant indicated in his/her patient diary was in accordance with the dose which could be calculated based upon the participant's blood glucose target, current blood glucose value, and the ISF. | Baseline to Week 24 | 
| Change in Carbohydrate Counting Accuracy From Baseline to Week 24 | Participants were asked to assess the carbohydrate content (grams) of 10 standardized meals by using a set of Dose Adjustment for Normal Eating (DAFNE) plates, which provide standardized photographs of meals with known carbohydrate values. The mean meal error (MME), an indicator of accuracy, and mean meal absolute error (MMAE), an indicator of variability were calculated from their responses. The MME is defined as the mean of the differences between the estimated carbohydrate content and the actual carbohydrate content over the 10 DAFNE plates. A negative MME indicates an underestimation and a positive MME indicates an overestimation of the actual carbohydrate content. The MMAE is defined as the mean of the absolute value of the differences between the estimated carbohydrate content and the actual carbohydrate content over the 10 DAFNE plates. The MMAE is ≥ 0 with a lower value indicating a better ability to estimate the actual carbohydrate content. | Baseline to Week 24 | 
| Change in the Patient Health Questionnaire Depression Scale (PHQ-8) Score From Baseline to Week 24 | The Patient Health Questionnaire depression scale (PHQ-8) contains 8 items which can be rated from 0='not at all' to 3='nearly every day'. The total PHQ-8 score is the sum of the responses to the 8 items and ranges from 0 to 24. A lower score indicates less depression. A negative change score indicates improvement. | Baseline to Week 24 | 
| Number of Participants With None, Mild, Moderate, Moderately Severe, and Severe Depression at Baseline and Week 24 | The Major Depression Disorder (MDD) scale is derived from the Patient Health Questionnaire depression scale (PHQ-8) and was used to categorize participants in regard to the severity of their depression. There are 5 categories on the MDD scale: None, mild, moderate, moderately severe, and severe. The category for each participant is determined from their PHQ-8 score. A total PHQ-8 score of 0 to 4 represents no significant depressive symptoms. A total PHQ-8 score of 5 to 9 represents mild depressive symptoms; 10 to 14, moderate; 15 to 19, moderately severe; and 20 to 24, severe. A higher score indicates more depression. | Baseline to Week 24 | 
| Change in the Problem Area in Diabetes (PAID) Scale Score From Baseline to Week 24 | The Problem Area in Diabetes (PAID) scale contains 20 items which can be rated from 0='not a problem' to 4='serious problem'. The total PAID scale score ranges from 0 to 80 with a higher score indicating more diabetes-related problems. A negative change score indicates improvement. | Baseline to Week 24 | 
| Change in the Hypoglycemia Fear Survey (HFS-II) Score From Baseline to Week 24 | The Hypoglycemia Fear Survey-II (HFS-II) contains 33 items (15 items regarding behavior and 18 items regarding worry) which can be rated from 0='never' to 4='always'). The total HFS-II score ranges from 0 to 132 with a higher score indicating more fear. A negative change score indicates improvement. | Baseline to Week 24 | 
| The Diabetes Treatment Satisfaction Questionnaire at Baseline (DTSQs) Score and the Diabetes Treatment Satisfaction Questionnaire for Change From Baseline (DTSQc) Score | The Diabetes Treatment Satisfaction Questionnaire at Baseline (DTSQs) contains 6 items which can be scored from 0='very bad' to 6='very good'. The total score is the sum of the scores of the 6 items and ranges from 0 to 36. A higher score indicates more satisfaction. This questionnaire was administered at Baseline only. The Diabetes Treatment Satisfaction Questionnaire for change from Baseline (DTSQc) to study end contains 6 items which can be rated from -3='much worse now' to 3='much better now'). The total score is the sum of the scores of the 6 items and ranges from -18 to 18. A higher score indicates more satisfaction. This questionnaire was administered at the end of the study (Week 24) only. | Baseline to Week 24 |