Adapting Diabetes Treatment Expert Systems to Patient in Type 1 Diabetes

Study Overview
=================
Brief Summary
-----------------
This study is evaluate the superior efficacy of a Continuous Glucose Monitor (CGM)-based advisory system in Type 1 Diabetes Mellitus (T1DM), as compared to Sensor Augmented Mode (SAM) therapy, and with characterizing the impact of psycho-behavioral factors on system performance, which will enable system individualization and lead to automated adaptation of advice delivery to optimize glycemic control and reduce the system's psychological impact.

Detailed Description
-----------------
Four cohorts of about 25 participants each (expected retention 20 per cohort). Each cohort will continue for  7 months. Following recruitment, screening, and a run-in period of SAM, participants will be randomized into one of two groups: escalation vs. de-escalation of devices and function. Each treatment modality (SAM - Sensor-Augmented Mode, PF - Personalized Feedback, DSS - Decision Support Systems) will continue for about 8 weeks, with the last 4 weeks used to assess glucose variability (GV) from CGM data.

Official Title
-----------------
Adapting Diabetes Treatment Expert Systems to Patient's Expectations and Psychobehavioral Characteristics in Type 1 Diabetes

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

Intervention / Treatment
-----------------
* Device: Personalized Feedback
* Device: Decision Support System
* Device: Sensor Augmented Mode


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18 years and older Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least one year and using insulin for at least one year HbA1c 6.0-11.0%, inclusive Demonstration of proper mental status and cognition for the study If on a non-insulin hyperglycemic therapy, stability on that therapy for the prior 3 months and willingness not to alter the therapy for the study duration. For females, not currently known to be pregnant If female and sexually active, must agree to use a highly effective form of contraception to prevent pregnancy while a participant in the study. A negative serum or urine pregnancy test will be required for all premenopausal women who are not surgically sterile. Subjects who become pregnant will be discontinued from the study. Also, subjects who during the study develop and express the intention to become pregnant within the timespan of the study will be discontinued. Subjects must have Internet access and a computer system that meets the requirements for uploading the study equipment and ability to participate in video conferencing. Investigator has confidence that the subject can successfully operate all study devices and is capable of adhering to the protocol Exclusion Criteria: NPH (neutral protamine hagedorn) insulin Use of any medication that at the discretion of the investigator is deemed to interfere with the trial. Current treatment of a primary seizure disorder Coronary artery disease or heart failure, unless written clearance is received from a cardiologist. Hemophilia or any other bleeding disorder A known medical condition, which in the opinion of the investigator or designee, would put the participant or study at risk such as the following examples: Inpatient psychiatric treatment in the past 6 months Presence of a known adrenal disorder Abnormal liver function test results (Transaminase >3 times the upper limit of normal) Abnormal renal function test results (calculated GFR <60 mL/min/1.73m2). Active gastroparesis requiring medical therapy Uncontrolled thyroid disease (TSH undetectable or >10 mlU/L). Abuse of alcohol or recreational drugs Infectious process not anticipated to be resolved prior to study procedures (e.g. meningitis, pneumonia, osteomyelitis, deep tissue infection). Uncontrolled arterial hypertension (Resting diastolic blood pressure >100 mmHg and/or systolic blood pressure >180 mmHg). Uncontrolled microvascular complications such as current active proliferative diabetic retinopathy defined as proliferative retinopathy requiring treatment (e.g. laser therapy or VEGF inhibitor injections) in the past 12 months. A recent injury to body or limb, muscular disorder, use of any medication, any carcinogenic disease, or other significant medical disorder if that injury, medication or disease in the judgment of the investigator will affect the completion of the protocol. Not familiar with smart phone technology Current use of the following drugs and supplements: Oral steroids Any other medication that the investigator believes is a contraindication to the subject's participation Participation in another pharmaceutical or device trial at the time of enrollment or during the study.

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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: De-escalation<br>Subjects randomized to this arm will proceed from DSS to PF to SAM | Device: Personalized Feedback<br>* Provides tailored information to the user about what glycemic risk they may be facing as well as how glycemic control and system use looked in the past week. Treatment decision and therapy changes are entirely left to the decision of the user.<br>Device: Decision Support System<br>* CGM-based system that includes Personalized Feedback (PF) and further assists with treatment recommendations for common metabolic challenges<br>Device: Sensor Augmented Mode<br>* A mode in Diabetes Assistant (DiAs) that combines Diabetes Assistant, Insulin pump or Multiple Daily Injections, CGM, ketone meters, and glycemic treatment guidelines together to manage diabetes.<br>|
| Experimental: Escalation<br>Subjects randomized to this arm will proceed from SAM to PF to DSS | Device: Personalized Feedback<br>* Provides tailored information to the user about what glycemic risk they may be facing as well as how glycemic control and system use looked in the past week. Treatment decision and therapy changes are entirely left to the decision of the user.<br>Device: Decision Support System<br>* CGM-based system that includes Personalized Feedback (PF) and further assists with treatment recommendations for common metabolic challenges<br>Device: Sensor Augmented Mode<br>* A mode in Diabetes Assistant (DiAs) that combines Diabetes Assistant, Insulin pump or Multiple Daily Injections, CGM, ketone meters, and glycemic treatment guidelines together to manage diabetes.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycemic Outcomes | Glucose Variability (GV) as measured by CGM-based Coefficient of Variation (CV), as recommended by the International Consensus on Use of Continuous Glucose Monitoring. | 7 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| percent time in clinical hypoglycemia | percent time spent below 54mg/dL as per CGM | 7 months | 
| percent time below recommended threshold | percent time spent below 70mg/dL as per CGM | 7 months | 
| percent time in target range | percent time spent between 70mg/dL and 180mg/dL as per CGM | 7 months | 
| percent time above range | percent time spent above 180mg/dL as per CGM | 7 months | 
| percent time above 250 mg/dL | percent time spent above 250mg/dL as per CGM | 7 months | 
| average glycemia | average of CGM values | 7 months | 
| Low Blood Glucose Index | average of hypoglycemia risk value per Kovatchev et al 1998 as per CGM | 7 months | 
| High Blood Glucose Index | average of hyperglycemia risk value per Kovatchev et al 1998 as per CGM | 7 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Behavior, Continuous Glucose Monitor (CGM), Insulin Pump, Decision Support System (DSS), Personalized Feedback (PF), Sensor Augmented Pump therapy (SAP), Multiple Daily Injections (MDI), Sensor Augmented Mode (SAM), Continuous Subcutaneous Insulin Infusion (CSII)