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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomized Comparison of Transitioning From Insulin GLargine to Insulin Degludec usING a Bridging Dose of Glargine Versus Direct Conversion, in Patients With Type 1 Diabetes Mellitus - a Pilot Study

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Drug: Insulin Degludec
* Drug: Insulin Glargine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must meet ALL inclusion criteria to be included in the study. Patient age is 18-75 years. Diagnosis of T1D of at least 1-year duration. Has the ability to provide informed consent before any trial-related activities. Treated with insulin glargine as their basal insulin in the 3 months preceding screening visit. 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. Patient willing to dose their basal insulin at bedtime. Hemoglobin A1c < 9% in the 3 months preceding screening visit. Able to self-administer their insulin doses. 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. 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. Will be reachable by phone and/or email to comply with study procedures. Will be able to comply with study procedures, per investigator's opinion. Patient agrees to not use correctional insulin unless BG ≥250 for the 48 hours before and after 1st dose of IDeg. Exclusion Criteria: Patient must not have ANY of the exclusion criteria to be included in the study. Patients with eGFR <30 on at least 2 measurements within 1-year of the screening visit. History of myocardial infarction within 6 months preceding the screening visit. 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) Known or suspected allergy to IDeg or one of its excipients. Pregnant, planning to become pregnant in the next 3 months or breastfeeding. Participation in a clinical trial with investigational drug within 1 month of the screening visit or at present. Skin condition that prevents the insertion of the CGM. Previously randomized and received drug in this study. Presence of decompensated or poorly controlled psychiatric conditions. Current known or suspected illicit substance use. Any anticipated surgery or procedure in the next 14 days. Patients using U-300 glargine as their basal insulin. Patients using insulin afrezza as their short-acting insulin. Use of glucocorticoid burst/pulse therapy within 14 days prior to screening visit (chronic stable glucocorticoid doses are acceptable).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Insulin Glargine and Insulin Degludec<br>Insulin glargine, 100 units per mL injected subcutaneously daily Insulin Degludec, 100 units per mL injected subcutaneously daily | Drug: Insulin Degludec<br>* Insulin Degludec injection<br>* Other names: Tresiba;Drug: Insulin Glargine<br>* Insulin Glargine injection<br>* Other names: Lantus;|
| Placebo Comparator: Insulin Degludec and placebo<br>Insulin Degludec, 100 units per mL injected subcutaneously daily Placebo, 9g/L sodium chloride (normal saline) injected subcutaneously daily | Drug: Insulin Degludec<br>* Insulin Degludec injection<br>* Other names: Tresiba;Drug: Placebo<br>* 9g/L sodium chloride (normal saline) subcutaneous injection manufactured to mimic insulin glargine injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in percent time in range | Change in percent time spent in target glycemic range (TIR, glucose 70-180 mg/dL, both values included) in the 48 hours before and the 48 hours after the 1st dose of IDeg. | 4 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Coefficient of variation (CV) of percent-time-in-range | Change in CV in the 48 hours before and the 48 hours after the 1st dose of IDeg. | 4 days | 
| Nocturnal percent time in range of 70-180 mg/dL | Change in the nocturnal percent time in range in the 48 hours before and the 48 hours after the 1st dose of IDeg. | 4 days | 
| Percent time above 180 mg/dL (TAR-1), percent time above 250 mg/dL (TAR-2) | Change in the percent time above range (TAR-1, TAR-2) in the 48 hours before and the 48 hours after the 1st dose of IDeg. | 4 days | 
| Percent time below 70 mg/dL (TBR-1), percent time below 54 mg/dL (TBR-2) | Change in the percent time below range (TBR-1, TBR-2) in the 48 hours before and the 48 hours after the 1st dose of IDeg. | 4 days | 
| Number of correction boluses | Change in the absolute number of correction boluses in the 48 hours before and the 48 hours after the 1st dose of IDeg. | 4 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Insulin glargine, insulin degludec