TRANSITION: Insulin Pump to Multiple Daily Injection Transition Clinical Trial

• Sponsor: University of Colorado, Denver (Other)
• Overall Status: Completed
• CT.gov ID: NCT03987191
• Collaborator: (none)
• Enrollment: 38
• Location: 1
• Arms: 2
• Actual Duration (Months): 8.9
• Patients Per Site Per Month: 4.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Type 1 Diabetes	Drug: Multiple daily ijnection using Insulin Degludec and Insulin Aspart	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 38 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Successful Transition From Insulin Pump to Multiple Daily Injections Using Insulin Degludec in Adults With Type 1 Diabetes
• Actual Study Start Date: Jan 10, 2020
• Actual Primary Completion Date: Oct 8, 2020
• Actual Study Completion Date: Oct 8, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Time Spent With CGM Glucose Levels >180mg/dl Between Two Groups [7 days from the randomization]

   The primary outcome will be time spent in CGM glucose >180 mg/dL (hyperglycemia) during 7days of randomization period between two groups.

Secondary Outcome Measures

1. Time Spent in CGM-measured "Time-in-range"(Glucose Levels ≥70 mg /dl and ≤180 mg/dl) Between Two Groups [7 days from the randomization]

   CGM TIR between two groups

2. Time Spent in CGM-measured Hypoglycemia < 70 mg/dl Between Two Groups [7 days from the randomization]

   CGM time below 70 between two groups

3. 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 [7 days from the randomization]

   Frequency of SH and DKA between two groups

4. Number of Boluses (Correction Boluses) Between Groups During First 72 Hours of Randomization [72 hours from the randomization]

   no of correction boluses between two groups

5. Insulin Delivery Satisfaction (IDSS Survey) Between Two Groups [7 days from the randomization]

   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.

6. Work Productivity and Activity Impairment (WPAI:SHP Version 2 Questionnaire) Between Two Groups [7 days from the randomization]

   PRO between two groups

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Barbara Davis Center for Diabetes	Aurora	Colorado	United States	80045

Sponsors and Collaborators

• University of Colorado, Denver

Investigators

• Principal Investigator: Viral Shah, MD, University of Colorado, Denver

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 31, 2020

More Information

Publications

None provided.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT03987191
• Other Study ID Numbers: 19-0924
• First Posted: Jun 14, 2019
• Last Update Posted: Sep 13, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Diabetes Mellitus, Type 1; Insulin; Insulin Aspart; Insulin degludec, insulin aspart drug combination

Study Results

Participant Flow

Pre-assignment Detail	3 screen failed, 1 participant was lost to follow-up prior to screening, and 2 withdrew from study prior to randomization.

Arm/Group Title	Standard of Care Transition	Investigational Transition
Arm/Group Description	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 Multiple daily ijnection using Insulin Degludec and Insulin Aspart: Drug: Insulin Degludec and insulin Aspart Pharmaceutical form: Solution for injection Route of administration: Subcutaneous	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 Multiple daily ijnection using Insulin Degludec and Insulin Aspart: Drug: Insulin Degludec and insulin Aspart Pharmaceutical form: Solution for injection Route of administration: Subcutaneous
Period Title: Overall Study
STARTED	17	15
Data Collected	17	13
COMPLETED	17	13
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	Standard of Care Transition	Investigational Transition	Total
Arm/Group Description	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 Multiple daily ijnection using Insulin Degludec and Insulin Aspart: Drug: Insulin Degludec and insulin Aspart Pharmaceutical form: Solution for injection Route of administration: Subcutaneous	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 Multiple daily ijnection using Insulin Degludec and Insulin Aspart: Drug: Insulin Degludec and insulin Aspart Pharmaceutical form: Solution for injection Route of administration: Subcutaneous	Total of all reporting groups
Overall Participants	17	13	30
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	35.7 (9.1)	38.2 (9.5)	36.8 (9.2)
Sex: Female, Male (Count of Participants)
Female	9 52.9%	6 46.2%	15 50%
Male	8 47.1%	7 53.8%	15 50%
Race/Ethnicity, Customized (Number of participants) [Number]
White	15 88.2%	13 100%	28 93.3%
Other	2 11.8%	0 0%	2 6.7%
Region of Enrollment (participants) [Number]
United States	17 100%	13 100%	30 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard of Care Transition	Investigational Transition
Arm/Group Description	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 Multiple daily ijnection using Insulin Degludec and Insulin Aspart: Drug: Insulin Degludec and insulin Aspart Pharmaceutical form: Solution for injection Route of administration: Subcutaneous	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 Multiple daily ijnection using Insulin Degludec and Insulin Aspart: Drug: Insulin Degludec and insulin Aspart Pharmaceutical form: Solution for injection Route of administration: Subcutaneous
Measure Participants	17	13
Median (Inter-Quartile Range) [percentage of time spent >180 mg/dL]	46.3	38.5

2. Secondary Outcome

Title	Time Spent in CGM-measured "Time-in-range"(Glucose Levels ≥70 mg /dl and ≤180 mg/dl) Between Two Groups
Description	CGM TIR between two groups
Time Frame	7 days from the randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard of Care Transition	Investigational Transition
Arm/Group Description	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 Multiple daily ijnection using Insulin Degludec and Insulin Aspart: Drug: Insulin Degludec and insulin Aspart Pharmaceutical form: Solution for injection Route of administration: Subcutaneous	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 Multiple daily ijnection using Insulin Degludec and Insulin Aspart: Drug: Insulin Degludec and insulin Aspart Pharmaceutical form: Solution for injection Route of administration: Subcutaneous
Measure Participants	17	13
Median (Inter-Quartile Range) [percentage of time spent in range]	47.8	56.5

3. Secondary Outcome

Title	Time Spent in CGM-measured Hypoglycemia < 70 mg/dl Between Two Groups
Description	CGM time below 70 between two groups
Time Frame	7 days from the randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard of Care Transition	Investigational Transition
Arm/Group Description	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 Multiple daily ijnection using Insulin Degludec and Insulin Aspart: Drug: Insulin Degludec and insulin Aspart Pharmaceutical form: Solution for injection Route of administration: Subcutaneous	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 Multiple daily ijnection using Insulin Degludec and Insulin Aspart: Drug: Insulin Degludec and insulin Aspart Pharmaceutical form: Solution for injection Route of administration: Subcutaneous
Measure Participants	17	13
Median (Inter-Quartile Range) [percentage of time below range]	3.9	2.1

4. Secondary Outcome

Title	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
Description	Frequency of SH and DKA between two groups
Time Frame	7 days from the randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard of Care Transition	Investigational Transition
Arm/Group Description	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 Multiple daily ijnection using Insulin Degludec and Insulin Aspart: Drug: Insulin Degludec and insulin Aspart Pharmaceutical form: Solution for injection Route of administration: Subcutaneous	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 Multiple daily ijnection using Insulin Degludec and Insulin Aspart: Drug: Insulin Degludec and insulin Aspart Pharmaceutical form: Solution for injection Route of administration: Subcutaneous
Measure Participants	17	13
Participants with Severe Hypoglycemia	0 0%	0 0%
Participants with Diabetic Ketoacidosis	0 0%	0 0%

5. Secondary Outcome

Title	Number of Boluses (Correction Boluses) Between Groups During First 72 Hours of Randomization
Description	no of correction boluses between two groups
Time Frame	72 hours from the randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard of Care Transition	Investigational Transition
Arm/Group Description	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 Multiple daily ijnection using Insulin Degludec and Insulin Aspart: Drug: Insulin Degludec and insulin Aspart Pharmaceutical form: Solution for injection Route of administration: Subcutaneous	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 Multiple daily ijnection using Insulin Degludec and Insulin Aspart: Drug: Insulin Degludec and insulin Aspart Pharmaceutical form: Solution for injection Route of administration: Subcutaneous
Measure Participants	17	13
Median (Inter-Quartile Range) [Boluses per day]	6.5	4.0

6. Secondary Outcome

Title	Insulin Delivery Satisfaction (IDSS Survey) Between Two Groups
Description	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.
Time Frame	7 days from the randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard of Care Transition	Investigational Transition
Arm/Group Description	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 Multiple daily ijnection using Insulin Degludec and Insulin Aspart: Drug: Insulin Degludec and insulin Aspart Pharmaceutical form: Solution for injection Route of administration: Subcutaneous	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 Multiple daily ijnection using Insulin Degludec and Insulin Aspart: Drug: Insulin Degludec and insulin Aspart Pharmaceutical form: Solution for injection Route of administration: Subcutaneous
Measure Participants	17	13
Median (Inter-Quartile Range) [score on a scale]	3.9	3.9

7. Secondary Outcome

Title	Work Productivity and Activity Impairment (WPAI:SHP Version 2 Questionnaire) Between Two Groups
Description	PRO between two groups
Time Frame	7 days from the randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard of Care Transition	Investigational Transition
Arm/Group Description	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 Multiple daily ijnection using Insulin Degludec and Insulin Aspart: Drug: Insulin Degludec and insulin Aspart Pharmaceutical form: Solution for injection Route of administration: Subcutaneous	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 Multiple daily ijnection using Insulin Degludec and Insulin Aspart: Drug: Insulin Degludec and insulin Aspart Pharmaceutical form: Solution for injection Route of administration: Subcutaneous
Measure Participants	17	13
Percent work time missed due to problem	0.0	0.0
Percent impairment while working	0.2	0.2
Percent overall work impairment	1.0	1.0
Percent activity impairment due to problem	0.1	0.2

Adverse Events

Time Frame	7 Days
Arm/Group Title	Standard of Care Transition		Investigational Transition
Arm/Group Description	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 Multiple daily ijnection using Insulin Degludec and Insulin Aspart: Drug: Insulin Degludec and insulin Aspart Pharmaceutical form: Solution for injection Route of administration: Subcutaneous		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 Multiple daily ijnection using Insulin Degludec and Insulin Aspart: Drug: Insulin Degludec and insulin Aspart Pharmaceutical form: Solution for injection Route of administration: Subcutaneous
All Cause Mortality
	Standard of Care Transition		Investigational Transition
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/13 (0%)
Serious Adverse Events
	Standard of Care Transition		Investigational Transition
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	Standard of Care Transition		Investigational Transition
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		2/13 (15.4%)
Respiratory, thoracic and mediastinal disorders
AE unrelated to the study	0/17 (0%)	0	2/13 (15.4%)	2

Limitations/Caveats

Single Center study with small sample size

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.