Glycemic Stability of Insulin Aspart Versus Insulin Lispro in Insulin Pump Therapy

Study Overview
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Brief Summary
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The purpose of this study is to determine: whether there is a difference between insulin aspart and insulin lispro in continuous insulin pump therapy whether duration of the insulin infusion set placement effect blood sugar control if the infusion set is in place for longer then 72-96 hours

Detailed Description
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Insulin instability in pump infusion systems can result in unexplained hyperglycemia in patients on continuous subcutaneous insulin infusion (CSII) therapy. We have noted that some pump patients develop glycemic instability with use of insulin lispro, and that this resolves with change to insulin aspart. Several patients using lispro have reported noting a whitish precipitate in the infusion set, and in two cases we have examined the catheters and confirmed biochemically that this precipitate was insulin. Furthermore, in vitro studies indicate that insulin aspart is more resistant to isoelectric precipitation than insulin lispro. Although it has been rare for patients to notice a visible precipitate in the pump catheter, there is a subset of patients using lispro who have noted that their blood glucose levels will tend to rise 2 or more days after the insertion of a new pump infusion system. These findings mirror bench studies showing that the relative stability differences between aspart and lispro in pump infusion systems becomes more apparent over time. The endpoints examined in previous randomized clinical trials comparing aspart and lispro were not directed specifically at assessing the effect of insulin type on glycemic stability. In these previous studies, pump infusion systems were changed every 48 hours whereas most pump patients routinely replace their infusion catheters only every 72-96 hours; this discrepancy may account for the failure of these trials to demonstrate the difference in the stability of insulin aspart and lispro that has been noted in clinical practice. This investigator-initiated clinical trial is intended to assess the safety and efficacy of CSII with insulin aspart compared to insulin lispro with use of pump infusion catheters for up to 96 hours.

Official Title
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Glycemic Stability of Insulin Aspart Versus Insulin Lispro in Insulin Pump Therapy

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: Insulin Aspart versus Insulin Lispro
* Drug: Insulin Lispro versus Insulin Aspart


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 1 diabetes treated with CSII at least 3 months. Males and females, > 18 years but < 75 years old. Hemoglobin A1c ≤ 8.0 % at measurement taken at week 0 (screening visit). Duration of diabetes ≥ 12 months. Willingness to perform self-blood glucose monitoring several times/day. Exclusion Criteria: Previous insulin precipitation in pump infusion catheters. Daily insulin requirements > 25% of pump reservoir capacity. (This would preclude the subject from using the pump infusion system for more than 3 days). Use of an insulin pump that does not have a downloadable record of basal and bolus doses. Known or suspected allergy to trial products. Pregnancy, breast-feeding, intention to become pregnant or inadequate contraception measures. Known or suspected alcohol or drug abuse. Impaired renal function with creatinine ≥ 1.7 mg/dl. Pronounced catheter site scarring. Chronic use of drugs that may influence glycemic control (e.g. steroids). Any other significant concomitant disease that would interfere with participation in and completion of the trial.

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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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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Insulin Aspart Versus Insulin Lispro<br>Insulin aspart will be used for diabetes management, and will be delivered continuously, subcutaneously using a pump for a four week period. Insulin aspart doses will be adjusted by the principal investigator as needed to maintain glycemic control. Insulin dose adjustments will vary from patient to patient based on the carbohydrate consumption, level of physical activity, and fingerstick monitoring results SMBG (7 times per day). SMBG results collected during this four week period will be compared to the SMBG results collected while participant uses alternative treatment (insulin Lispro). | Drug: Insulin Aspart versus Insulin Lispro<br>* Subjects will be randomly assigned to insulin aspart versus insulin lispro via random number generation. Half of the patients will begin with insulin aspart, and then will be crossed over to insulin lispro. The insulin sequence will be reversed for the other half of the patients.<br>* Other names: Humalog;|
| Active Comparator: Insulin Lispro Versus Insulin Aspart<br>Insulin lispro will be used for diabetes management, and will be delivered continuously, subcutaneously using a pump for a four week period. Dose will be adjusted as needed to maintain glycemic control. Insulin dose adjustments will vary from patient to patient based on the carbohydrate consumption, level of physical activity, and fingerstick monitoring results SMBG (7 times per day). SMBG results collected during this four week period will be compared to the SMBG results collected while participant uses alternative treatment (insulin Aspart). | Drug: Insulin Lispro versus Insulin Aspart<br>* Subjects will be randomly assigned to insulin lispro versus insulin aspart via random number generation. Half of the patients will begin with insulin lispro, and then will be crossed over to insulin aspart. The insulin sequence will be reversed for the other half of the patients.<br>* Other names: Novolog;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycemic Stability | Glycemic stability will be assessed by MAGE (Mean Amplitude of Glycemic Excursion)(5), M value of Schlichtkrull, standard deviation & coefficient of variation using 7 point finger stick blood glucose measurements performed 48-96 hours after insertion of the pump infusion catheter. Data collected 48 to 72 hours post-catheter insertion will be analyzed separately from the data collected 72 to 96 hours post-catheter insertion. The mean of the measurements taken throughout the study will be used for calculation of the primary endpoint. | 48 to 96 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Catheter Change | Recorded by the subjects who will use a checklist to document the reason for the catheter change (routine, insufficient insulin in infusion system, unexplained hyperglycemia, catheter site irritation, suspected occlusion/kinking of catheter, loosening of catheter. | 48 to 96 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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type 1 diabetes, insulin pump therapy, glycemic stability