Glycemic Effects of Morning Only, Evening Only or Twice Daily Insulin Glargine in Patients With Type 1 Diabetes

Study Overview
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Brief Summary
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This research is a prospective, randomized, cross-over study that is being done to compare the effect of morning only, evening only and twice daily insulin glargine (Lantus®) on hypoglycemia (blood glucose level <70 mg/dL) as measured by continuous glucose monitoring (CGM) in patients with type 1 diabetes.

Detailed Description
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Over the course of the 6 week study, patients will take insulin glargine in each of 3 different times: only in the morning, only at night, and half in the morning, half at night. After 2 weeks taking the insulin in one regimen, patients will be switched to another regimen. Through the whole study, patients will be injecting themselves twice daily, and neither the patient nor the treating doctor will know which vials contain the insulin and which have only saline (placebo). The vials will be labeled MORNING or EVENING. Patients will continue to take their mealtime, short acting insulin doses. Additionally, patients will wear a continuous glucose monitor (CGM) which will be masked. Before the study, patients will be taught about how to use the CGM, and keep it taped to their abdomen. The site that the CGM inserts into their abdomen will need to be changed every 5 days. We will know if a patients' blood sugar goes low even if the patient did not feel the low. Patients will still have to self-monitor their blood sugar levels at-least four times in five days, to calibrate the CGM.

Official Title
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Comparison of Glycemic Response to Morning Only, Evening Only or Twice Daily Insulin Glargine in Patients With Type 1 Diabetes Using Continuous Glucose Monitoring

Conditions
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Type 1 Diabetes, Hypoglycemia

Intervention / Treatment
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* Drug: Evening only administration of insulin glargine
* Drug: Morning only administration of insulin glargine
* Drug: split dose insulin glargine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult men and women above age 18 with a diagnosis of type 1 diabetes mellitus On multiple insulin injections, including a long acting or intermediate acting insulin preparation and mealtime short acting insulin preparation. Clinical history consistent with hypoglycemia Hba1c <9.0% Exclusion Criteria: Patients with type 2 diabetes mellitus Patients on insulin pump Poor control of diabetes (HbA1c > 9.0%) Pregnancy (women of childbearing age will undergo a pregnancy test at the start of the study and will be advised to use birth control methods during the study). Insulin glargine has been reported to have teratogenic effects in animal models, and therefore should only be used during pregnancy if clearly needed. Serious co-morbidities that, in clinical opinion of the investigators, could affect pharmacokinetics of glargine (e.g., CRF) or safety (e.g., recent CAD)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: insulin glargine only in morning<br>Morning only administration of insulin glargine | Drug: Morning only administration of insulin glargine<br>* Morning only administration of insulin glargine, with normal saline injection administered at night.<br>* Other names: Lantus;|
| Active Comparator: insulin glargine only at evening<br>Evening only administration of insulin glargine | Drug: Evening only administration of insulin glargine<br>* Evening only administration of insulin glargine, with normal saline injection administered in the morning.<br>* Other names: Lantus;|
| Active Comparator: split dose insulin glargine<br>Split dose administration of insulin glargine, half dose in morning, half dose in evening | Drug: split dose insulin glargine<br>* split dose of insulin glargine, half administered in the morning, half administered in evening<br>* Other names: Lantus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time Spent (Mean Number of Minutes Per 24 Hour Day) in Hypoglycemic Range (<70mg/dl) |  | 6 weeks | 
| Change in the Mean Minutes Per 24 Hour Day in the Hyperglycemic Range of > 180 mg/dL. |  | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypoglycemia, type 1 diabetes, split dosing insulin glargine, continuous glucose monitoring