Insulin Pump to Multiple Daily Injection Transition Clinical Trial

Study Overview
=================
Brief Summary
-----------------
This randomized controlled, two arms, investigator initiated, intervention study is aimed to examine an investigational approach in contrast to the clinical standard of 1:1 dose basal insulin conversion in an attempt to lower the incidence and/or duration of hyperglycemia after transition from insulin pump to multiple daily injections in adults with type 1 diabetes.

Detailed Description
-----------------
Second generation long acting insulin, insulin degludec, has been shown to improve glycemic control and reduce hypoglycemia in patients with type 1 diabetes and insulin treated type 2 diabetes. However, it takes about 48 hours before glycemic benefits are noticeable. Therefore, transition from insulin pump to multiple daily injection using insulin degludec is associated with hyperglycemia during first 48 hours of transition. Considering this, this study proposes to evaluate an investigational strategy to improve glycemic control during transition from insulin pump to multiple daily injections using insulin degludec and insulin aspart.

Official Title
-----------------
Successful Transition From Insulin Pump to Multiple Daily Injections Using Insulin Degludec in Adults With Type 1 Diabetes

Conditions
-----------------
Type 1 Diabetes

Intervention / Treatment
-----------------
* Drug: Multiple daily ijnection using Insulin Degludec and Insulin Aspart


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥18 years and ≤ 65 years Patients with T1D diagnosed for at least 12 months Point-of-care HbA1c levels between ≥6.5% and ≤ 8.5% Patients on CSII (any insulin pump) for at least past 6 months Willing and able to wear a blinded CGM during the time of study period Willing to perform self-monitoring of blood glucose (SMBG) at least 4 times a day Ability to provide informed consent before any trial-related activities Not willing to or plan any travel out of Colorado during the 3 weeks of study period Willing to use insulin degludec in the morning once a day Exclusion Criteria: Age <18 years and > 65years HbA1c >8.5 % at screening Less than 12 months of insulin treatment Patients on 670G or Tandem Control IQ (Medtronic and Tandem Hybrid Closed-loop systems) and not willing use manual mode during the study period Patients with T1D using any glucose lowering medications other than insulin Pregnancy, breast feeding, and positive pregnancy test during screening Women of childbearing age wanting to become pregnant or not using adequate contraceptive measures Current or recent (< 2 weeks prior to visit 1) use of any steroidal medication, or anticipated steroidal treatment, during the study period eGFR below 45 ml/min/1.73 m^2 using MDRD formula History of severe hypoglycemia in the previous 3 months History of diabetic ketoacidosis (DKA) requiring hospitalization in the past 3 months History of allergy to any form of insulin or its excipients History of allergy to adhesives Unwilling to use blinded CGM during the study period Unwilling to perform SMPG at least 4 times a day Known history of alcohol abuse or illicit drug use within 6 months prior to screening Use of investigational drugs within 5 half-lives prior to screening Participation to other study trials during the study period Elevated liver enzymes (AST and ALT) 3 times the upper limit of normal Hypoglycemia unawareness defined as GOLD score ≥4 [20] Any comorbidities or medical conditions that make a person unfit for the study at the discretion of the investigators Anticipated travel across different time zones (difference greater than 4 hours) or anticipated change in physical activities or diet at the discretion of the investigators.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard of Care Transition<br>Stopping of insulin pump on the day of randomization and starting insulin degludec in 1:1 ratio (same units as total basal insulin on pump) and insulin Aspart for meals and corrections | Drug: Multiple daily ijnection using Insulin Degludec and Insulin Aspart<br>* Drug: Insulin Degludec and insulin Aspart Pharmaceutical form: Solution for injection Route of administration: Subcutaneous<br>|
| Experimental: Inverstigational Transition<br>Administration of insulin degludec in 1:1 ratio (same units as total basal insulin on pump) on the day of randomization AND concomitant use of the insulin pump for 48 hours from transition, where insulin pump basal rate will be reduced by 50% during the first 24 hours from transition and by 75% during 24 to 48 hours from transition. Insulin pump will be disconnected after 48 hours from transition | Drug: Multiple daily ijnection using Insulin Degludec and Insulin Aspart<br>* Drug: Insulin Degludec and insulin Aspart Pharmaceutical form: Solution for injection Route of administration: Subcutaneous<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time Spent With CGM Glucose Levels >180mg/dl Between Two Groups | The primary outcome will be time spent in CGM glucose >180 mg/dL (hyperglycemia) during 7days of randomization period between two groups. | 7 days from the randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time Spent in CGM-measured Time-in-range(Glucose Levels ≥70 mg /dl and ≤180 mg/dl) Between Two Groups | CGM TIR between two groups | 7 days from the randomization | 
| Time Spent in CGM-measured Hypoglycemia < 70 mg/dl Between Two Groups | CGM time below 70 between two groups | 7 days from the randomization | 
| Number of Participants With Severe Hypoglycemia as Defined by the ADA (Severe Cognitive Impairment Requiring External Assistance for Recovery) and Severe Hyperglycemia (BG≥250 Needing Hospitalization) Between Two Groups | Frequency of SH and DKA between two groups | 7 days from the randomization | 
| Number of Boluses (Correction Boluses) Between Groups During First 72 Hours of Randomization | no of correction boluses between two groups | 72 hours from the randomization | 
| Insulin Delivery Satisfaction (IDSS Survey) Between Two Groups | PRO between two groups. The Insulin delivery satisfaction survey (IDSS) measures diabetes patients' satisfaction with their insulin delivery system. Possible scores range from 1-5, with higher scores indicating higher satisfaction and a better outcome. | 7 days from the randomization | 
| Work Productivity and Activity Impairment (WPAI:SHP Version 2 Questionnaire) Between Two Groups | PRO between two groups | 7 days from the randomization |