Type 1 Diabetes
Conditions
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.
Interventions
DRUGMultiple daily ijnection using Insulin Degludec and Insulin Aspart
Drug: Insulin Degludec and insulin Aspart Pharmaceutical form: Solution for injection Route of administration: Subcutaneous
Sponsors
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Time Spent in CGM-measured Hypoglycemia < 70 mg/dl Between Two Groups | 7 days from the randomization | CGM time below 70 between two groups |
| 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 |
| 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 |
| 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. |
| Work Productivity and Activity Impairment (WPAI:SHP Version 2 Questionnaire) Between Two Groups | 7 days from the randomization | PRO between two groups |
| 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 |
Countries
United States
Participant flow
Pre-assignment details
3 screen failed, 1 participant was lost to follow-up prior to screening, and 2 withdrew from study prior to randomization.
Participants by arm
| Arm | Count |
|---|---|
| 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
Multiple daily ijnection using Insulin Degludec and Insulin Aspart: Drug: Insulin Degludec and insulin Aspart Pharmaceutical form: Solution for injection Route of administration: Subcutaneous | 17 |
| Investigational 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
Multiple daily ijnection using Insulin Degludec and Insulin Aspart: Drug: Insulin Degludec and insulin Aspart Pharmaceutical form: Solution for injection Route of administration: Subcutaneous | 13 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | COVID-19 related research disruption | 0 | 2 |
Baseline characteristics
| Characteristic | Standard of Care Transition | Investigational Transition | Total |
|---|---|---|---|
| Age, Continuous | 35.7 Years STANDARD_DEVIATION 9.1 | 38.2 Years STANDARD_DEVIATION 9.5 | 36.8 Years STANDARD_DEVIATION 9.2 |
| Race/Ethnicity, Customized Other | 2 Number of participants | 0 Number of participants | 2 Number of participants |
| Race/Ethnicity, Customized White | 15 Number of participants | 13 Number of participants | 28 Number of participants |
| Region of Enrollment United States | 17 participants | 13 participants | 30 participants |
| Sex: Female, Male Female | 9 Participants | 6 Participants | 15 Participants |
| Sex: Female, Male Male | 8 Participants | 7 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 13 |
| other Total, other adverse events | 0 / 17 | 2 / 13 |
| serious Total, serious adverse events | 0 / 17 | 0 / 13 |
Outcome results
Primary
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.
Time frame: 7 days from the randomization
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care Transition | Time Spent With CGM Glucose Levels >180mg/dl Between Two Groups | 46.3 percentage of time spent >180 mg/dL |
| Investigational Transition | Time Spent With CGM Glucose Levels >180mg/dl Between Two Groups | 38.5 percentage of time spent >180 mg/dL |
Secondary
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.
Time frame: 7 days from the randomization
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care Transition | Insulin Delivery Satisfaction (IDSS Survey) Between Two Groups | 3.9 score on a scale |
| Investigational Transition | Insulin Delivery Satisfaction (IDSS Survey) Between Two Groups | 3.9 score on a scale |
Secondary
Number of Boluses (Correction Boluses) Between Groups During First 72 Hours of Randomization
no of correction boluses between two groups
Time frame: 72 hours from the randomization
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care Transition | Number of Boluses (Correction Boluses) Between Groups During First 72 Hours of Randomization | 6.5 Boluses per day |
| Investigational Transition | Number of Boluses (Correction Boluses) Between Groups During First 72 Hours of Randomization | 4.0 Boluses per day |
Secondary
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
Time frame: 7 days from the randomization
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Standard of Care Transition | 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 | Participants with Severe Hypoglycemia | 0 Participants |
| Standard of Care Transition | 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 | Participants with Diabetic Ketoacidosis | 0 Participants |
| Investigational Transition | 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 | Participants with Severe Hypoglycemia | 0 Participants |
| Investigational Transition | 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 | Participants with Diabetic Ketoacidosis | 0 Participants |
Secondary
Time Spent in CGM-measured Hypoglycemia < 70 mg/dl Between Two Groups
CGM time below 70 between two groups
Time frame: 7 days from the randomization
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care Transition | Time Spent in CGM-measured Hypoglycemia < 70 mg/dl Between Two Groups | 3.9 percentage of time below range |
| Investigational Transition | Time Spent in CGM-measured Hypoglycemia < 70 mg/dl Between Two Groups | 2.1 percentage of time below range |
Secondary
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
Time frame: 7 days from the randomization
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care Transition | Time Spent in CGM-measured Time-in-range(Glucose Levels ≥70 mg /dl and ≤180 mg/dl) Between Two Groups | 47.8 percentage of time spent in range |
| Investigational Transition | Time Spent in CGM-measured Time-in-range(Glucose Levels ≥70 mg /dl and ≤180 mg/dl) Between Two Groups | 56.5 percentage of time spent in range |
Secondary
Work Productivity and Activity Impairment (WPAI:SHP Version 2 Questionnaire) Between Two Groups
PRO between two groups
Time frame: 7 days from the randomization
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Standard of Care Transition | Work Productivity and Activity Impairment (WPAI:SHP Version 2 Questionnaire) Between Two Groups | Percent work time missed due to problem | 0.0 Percent |
| Standard of Care Transition | Work Productivity and Activity Impairment (WPAI:SHP Version 2 Questionnaire) Between Two Groups | Percent impairment while working | 0.2 Percent |
| Standard of Care Transition | Work Productivity and Activity Impairment (WPAI:SHP Version 2 Questionnaire) Between Two Groups | Percent overall work impairment | 1.0 Percent |
| Standard of Care Transition | Work Productivity and Activity Impairment (WPAI:SHP Version 2 Questionnaire) Between Two Groups | Percent activity impairment due to problem | 0.1 Percent |
| Investigational Transition | Work Productivity and Activity Impairment (WPAI:SHP Version 2 Questionnaire) Between Two Groups | Percent activity impairment due to problem | 0.2 Percent |
| Investigational Transition | Work Productivity and Activity Impairment (WPAI:SHP Version 2 Questionnaire) Between Two Groups | Percent work time missed due to problem | 0.0 Percent |
| Investigational Transition | Work Productivity and Activity Impairment (WPAI:SHP Version 2 Questionnaire) Between Two Groups | Percent overall work impairment | 1.0 Percent |
| Investigational Transition | Work Productivity and Activity Impairment (WPAI:SHP Version 2 Questionnaire) Between Two Groups | Percent impairment while working | 0.2 Percent |