Comparison of Glargine to Degludec Insulin Transition With or Without a Bridging Glargine Dose

NCT ID: NCT04623086

Last Updated: 2024-02-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 59 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-14
• Study Completion Date: 2023-12-31

Brief Summary

This study evaluates direct switching vs use of a bridging dose from insulin glargine to insulin degludec in type 1 DM patients. Half of the participants will receive a bridging insulin glargine dose along with the 1st dose of degludec, while other half will receive a placebo and 1st dose of degludec.

Detailed Description

Insulin degludec (IDeg), an ultra-long-acting basal insulin, is increasingly used to treat patients with type 1 diabetes (T1D). IDeg has a half-life of 25 hours and duration of action exceeding 42 hours in patients with T1D and as a result does not require as stringent a dosing schedule as other basal insulins. However, steady state concentration of IDeg is not reached until 2 to 3 doses are administered daily, and this may result in greater glycemic variability in the 24 to 72 hours following the initiation of therapy with IDeg.

Our hypothesis is that among patients who transition from insulin glargine to IDeg, those who use a bridging dose of insulin glargine will not have a significant change, on average, in time spent in target glycemic range during the transition period, whereas, those transitioning directly to IDeg will have a significant change in this parameter. We further hypothesize that those using the bridging dose of insulin glargine will have less hypoglycemia, less hyperglycemia and need fewer correction boluses than the direct-conversion patients during the transition period.

Though IDeg is being increasingly used in clinical practice, there are no guidelines on what is the best way to transition patients from other long-acting insulins, such as glargine, to IDeg. The package insert recommends 1:1 dose conversion from other basal insulins to IDeg, but this does not account for the time taken by IDeg to achieve steady state (typically 48-72 hours). There is no guidance on what to do in those 48-72 hours. Given the time taken for IDeg to achieve steady state, the period of transition from one insulin to another, can result in significant glycemic variation in the 24-72 hours after the first dose. We want to study how best to avoid or minimize this and the option of using a small dose of their original long-acting insulin has anecdotal evidence of success in our practice.

Conditions

Type 1 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Insulin Glargine and Insulin Degludec

Insulin glargine, 100 units per mL injected subcutaneously daily Insulin Degludec, 100 units per mL injected subcutaneously daily

Group Type: EXPERIMENTAL

Insulin Degludec

Intervention Type: DRUG

Insulin Degludec injection

Insulin Glargine

Intervention Type: DRUG

Insulin Glargine injection

Insulin Degludec and placebo

Insulin Degludec, 100 units per mL injected subcutaneously daily Placebo, 9g/L sodium chloride (normal saline) injected subcutaneously daily

Group Type: PLACEBO_COMPARATOR

Insulin Degludec

Intervention Type: DRUG

Insulin Degludec injection

Placebo

Intervention Type: DRUG

9g/L sodium chloride (normal saline) subcutaneous injection manufactured to mimic insulin glargine injection

Interventions

Insulin Degludec

Insulin Degludec injection

Intervention Type: DRUG

Insulin Glargine

Insulin Glargine injection

Intervention Type: DRUG

Placebo

9g/L sodium chloride (normal saline) subcutaneous injection manufactured to mimic insulin glargine injection

Intervention Type: DRUG

Other Intervention Names

Tresiba; Lantus

Eligibility Criteria

Inclusion Criteria

1. Patient age is 18-75 years.

2. Diagnosis of T1D of at least 1-year duration.

3. Has the ability to provide informed consent before any trial-related activities.

4. Treated with insulin glargine as their basal insulin in the 3 months preceding screening visit.

5. Stable insulin regimen (defined as change of <20% in the total daily dose of insulin and no change to the basal insulin agent) over the 3 months preceding the screening visit.

6. Patient willing to dose their basal insulin at bedtime.

7. Hemoglobin A1c < 9% in the 3 months preceding screening visit.

8. Able to self-administer their insulin doses.

9. Able to do self-monitoring of blood glucose using a glucose meter and willing to do this at least 2 times daily for patients using a CGM that requires calibration prior to the study and 4 times daily for patients who were not using a CGM prior to the study.

10. Agreeable to the use of a continuous glucose monitor (CGM) for the duration required in the study. If already using a CGM prior to the study, then agreeable to wearing the blinded study CGM concurrently during the study period.

11. Will be reachable by phone and/or email to comply with study procedures.

12. Will be able to comply with study procedures, per investigator's opinion.

13. Patient agrees to not use correctional insulin unless BG ≥250 for the 48 hours before and after 1st dose of IDeg.

Exclusion Criteria

1. Patients with eGFR <30 on at least 2 measurements within 1-year of the screening visit.

2. History of myocardial infarction within 6 months preceding the screening visit.

3. Patients taking non-insulin medications for the glycemic management of T1D (including metformin, DPP-4 inhibitors, GLP-1 receptor agonists, SGLT-2 inhibitors, thiazolidinediones, alpha-glucosidase inhibitors, pramlintide)

4. Known or suspected allergy to IDeg or one of its excipients.

5. Pregnant, planning to become pregnant in the next 3 months or breastfeeding.

6. Participation in a clinical trial with investigational drug within 1 month of the screening visit or at present.

7. Skin condition that prevents the insertion of the CGM.

8. Previously randomized and received drug in this study.

9. Presence of decompensated or poorly controlled psychiatric conditions.

10. Current known or suspected illicit substance use.

11. Any anticipated surgery or procedure in the next 14 days.

12. Patients using U-300 glargine as their basal insulin.

13. Patients using insulin afrezza as their short-acting insulin.

14. Use of glucocorticoid burst/pulse therapy within 14 days prior to screening visit (chronic stable glucocorticoid doses are acceptable).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Washington

OTHER

Sponsor Role: lead

Responsible Party

Arthi Thirumalai

Assistant Professor, School of Medicine: Metabolism, Endocrinology and Nutrition

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Arthi Thirumalai, MD

Role: PRINCIPAL_INVESTIGATOR

University of Washington

Locations

University of Washington Medicine Diabetes Institute at South Lake Union

Seattle, Washington, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

STUDY00008108

Identifier Type: -

Identifier Source: org_study_id