Insulin Pump to Multiple Daily Injection Transition Clinical Trial (TRANSITION)

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

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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Drug: Multiple daily ijnection using Insulin Degludec and Insulin Aspart

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.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Barbara Davis Center for Diabetes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥18 years and ≤ 65 years
2. Patients with T1D diagnosed for at least 12 months
3. Point-of-care HbA1c levels between ≥6.5% and ≤ 8.5%
4. Patients on CSII (any insulin pump) for at least past 6 months
5. Willing and able to wear a blinded CGM during the time of study period
6. Willing to perform self-monitoring of blood glucose (SMBG) at least 4 times a day
7. Ability to provide informed consent before any trial-related activities
8. Not willing to or plan any travel out of Colorado during the 3 weeks of study period
9. Willing to use insulin degludec in the morning once a day

Exclusion Criteria:

1. Age <18 years and > 65years
2. HbA1c >8.5 % at screening
3. Less than 12 months of insulin treatment
4. Patients on 670G or Tandem Control IQ (Medtronic and Tandem Hybrid Closed-loop systems) and not willing use manual mode during the study period
5. Patients with T1D using any glucose lowering medications other than insulin
6. Pregnancy, breast feeding, and positive pregnancy test during screening
7. Women of childbearing age wanting to become pregnant or not using adequate contraceptive measures
8. Current or recent (< 2 weeks prior to visit 1) use of any steroidal medication, or anticipated steroidal treatment, during the study period
9. eGFR below 45 ml/min/1.73 m^2 using MDRD formula
10. History of severe hypoglycemia in the previous 3 months
11. History of diabetic ketoacidosis (DKA) requiring hospitalization in the past 3 months
12. History of allergy to any form of insulin or its excipients
13. History of allergy to adhesives
14. Unwilling to use blinded CGM during the study period
15. Unwilling to perform SMPG at least 4 times a day
16. Known history of alcohol abuse or illicit drug use within 6 months prior to screening
17. Use of investigational drugs within 5 half-lives prior to screening
18. Participation to other study trials during the study period
19. Elevated liver enzymes (AST and ALT) 3 times the upper limit of normal
20. Hypoglycemia unawareness defined as GOLD score ≥4 [20]
21. Any comorbidities or medical conditions that make a person unfit for the study at the discretion of the investigators
22. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard of Care Transition; 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; Drug: Insulin Degludec and insulin Aspart Pharmaceutical form: Solution for injection Route of administration: Subcutaneous
Experimental: Inverstigational Transition; 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; Drug: Insulin Degludec and insulin Aspart Pharmaceutical form: Solution for injection Route of administration: Subcutaneous

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

Collaborators and Investigators

• Sponsor: University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2020
• Primary Completion (Actual): October 8, 2020
• Study Completion (Actual): October 8, 2020

Study Registration Dates

• First Submitted: June 5, 2019
• First Submitted That Met QC Criteria: June 13, 2019
• First Posted (Actual): June 14, 2019

Study Record Updates

• Last Update Posted (Actual): September 13, 2021
• Last Update Submitted That Met QC Criteria: September 9, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin Aspart; Insulin degludec, insulin aspart drug combination
• Other Study ID Numbers: 19-0924

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Qualified academic researchers may request access to de-identified participant level data related to the study. The request letter with details such as reasons for data request, plan for data analysis, publication and so on should be emailed/mailed to the PI of the study (viral.shah@cuanschutz.edu).
• IPD Sharing Time Frame: The data will be available after the publication. The data sharing details will be provided in the manuscript.
• IPD Sharing Access Criteria: The committee (PI, statistician and Sponsor) will decide on appropriate request for data sharing.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No