A Novel mHealth Application Guided by an Optimization Algorithm for T1D Sensor-Augmented Insulin Injection Users

Study Overview
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Brief Summary
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The Artificial Pancreas lab at McGill University has developed an optimization algorithm for adults with Type 1 Diabetes (T1D) on Multiple Daily Injection (MDI) therapy with the adjunctive use of glucose sensor technology, collectively known as sensor-augmented MDI therapy. The algorithm is designed to estimate optimal basal-bolus parameters based on the patient's glucose, insulin and meal data over several days. The investigators hope that this algorithm will be better able to improve long-term glycemic targets by reducing HbA1c levels compared to sensor-augmented MDI therapy alone.

Detailed Description
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The changes in eligibility criteria indicated below are from a previously approved amendment but were inadvertently omitted in the previous PRS update made in November of 2020. Therefore, this note serves to clarify the order of updates. Inclusion: HbA1c ≥ 7.5% in the last 2 months (modification) Exclusion: More than 1 slow-acting injection and unwilling to switch to once a day for the study (addition) Severe hypoglycemic episode within one month of admission (addition) In the subsequent amendment, we modified the timeframe for the HbA1c inclusion criterion to obtain a more accurate representation of their current glucose control at the time of enrollment.

Official Title
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An Open-Label, Randomized, Two-Way, Parallel Study to Compare the Effectiveness of Multiple Daily Injection Treatment With an Insulin Dose Optimization Algorithm in Free-Living Outpatient Conditions in Patients With Type 1 Diabetes

Conditions
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Diabetes Mellitus, Diabetes Mellitus, Type 1

Intervention / Treatment
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* Device: Mobile App
* Device: Mobile App + Basal-Bolus Optimization Algorithm


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females ≥ 18 years of age Clinical diagnosis of type 1 diabetes for at least 12 months. The diagnosis of type 1 diabetes is based on the investigator's judgment; C peptide level and antibody determinations are not needed. Undergoing multiple daily injection therapy. Baseline HbA1c value ≥ 7.5% (up to 7 days before or after screening). Exclusion Criteria: Serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator. Failure to comply with the study protocol or with the team's recommendations. Injection of isophane insulin (NPH) or any intermediate-acting insulin More than 1 slow-acting injection and unwilling to switch to once a day for the study Current or ≤ 1-month use of other antihyperglycemic agents (Sodium-Glucose Cotransporter 2 inhibitor (SGLT2), Glucagon-Like Peptide-1 (GLP-1), Metformin, Acarbose, etc.…). Pregnancy Severe hypoglycemic episode within one month of admission. Severe diabetic ketoacidosis episode within one month of admission Clinically significant nephropathy, neuropathy or retinopathy as judged by the investigator Recent (<6 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is an open-label, randomized, controlled, two-way parallel study to compare glucose control between sensor-augmented MDI therapy and our basal-bolus optimizing algorithm over 3 months. Adults with type 1 diabetes who are enrolled in the study will randomly undergo one of the two interventions for the entire study duration.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sensor-Augmented MDI + Mobile App (control)<br>Participants will continue their usual multiple daily injections (MDI) therapy along with the use of Freestyle Libre glucose sensors (Abbott Diabetes Care) and a mobile application that facilitates insulin dose calculations while collecting insulin and meal data. | Device: Mobile App<br>* Participants will use the mobile app to log their daily basal dose and calculate their meal doses by entering their sensor glucose value (and amount of meal carbohydrates if applicable) using the built-in bolus calculator.<br>|
| Experimental: Sensor-Augmented MDI + Mobile App + Basal-Bolus Optimization Algorithm<br>Participants will undergo multiple daily injections (MDI) therapy along with the use of Freestyle Libre glucose sensors (Abbott Diabetes Care) and a mobile application that facilitates insulin dose calculations while collecting insulin and meal data. Every week, participants' insulin doses will be updated by the optimization algorithm's recommendations. | Device: Mobile App + Basal-Bolus Optimization Algorithm<br>* Participants will use the mobile app to log their daily basal dose and calculate their meal doses by entering their sensor glucose value (and amount of meal carbohydrates if applicable) using the built-in bolus calculator. In addition, participants will receive weekly app notifications with personalized recommendations for insulin parameter adjustments made by the optimization algorithm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c levels | Difference in HbA1c levels from the start to the end of the study | Pre-intervention and post-intervention, approximately 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of patients that achieve an HbA1c at the end-of-study visit of: | a. less than or equal to 7.0%; b. less than or equal to 6.5% | Post-intervention, approximately 12 weeks | 
| Percentage of time of sensor glucose levels spent: | a. between 3.9 and 7.8 mmol/L; b.between 3.9 and 10 mmol/L; c. below 3.9 mmol/L; d.below 3.3 mmol/L; e.below 2.8 mmol/L; f. above 7.8 mmol/L; g. above 10 mmol/L; h. above 13.9 mmol/L; i. above 16.7 mmol/L. | 12 weeks | 
| Percentage of overnight time (23:00-7:00) of sensor glucose levels: | a. between 3.9 and 7.8 mmol/L; b. between 3.9 and 10 mmol/L; c.below 3.9 mmol/L; d. below 3.3 mmol/L; e. below 2.8 mmol/L; f. above 7.8 mmol/L; g. above 10 mmol/L; h. above 13.9 mmol/L; i. above 16.7 mmol/L. | 12 weeks | 
| Percentage of daytime (7:00-23:00) of sensor glucose levels: | a. between 3.9 and 7.8 mmol/L; b. between 3.9 and 10 mmol/L; c. below 3.9 mmol/L; d. below 3.3 mmol/L; e. below 2.8 mmol/L; f. above 7.8 mmol/L; g. above 10 mmol/L; h. above 13.9 mmol/L; i. above 16.7 mmol/L. | 12 weeks | 
| Standard deviation of glucose levels. | Standard deviation of glucose levels as a measure of glucose variability. | 12 weeks | 
| Total insulin delivery. | Total insulin delivery | 12 weeks | 
| Mean sensor glucose level during: | a. the overall study period; b. the daytime period; c. overnight period. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Daily Injections,, Type 1 diabetes, Optimization algorithm