Selecting Insulin Analogs for Closed-Loop Control Using Multiplex Pharmacokinetic Profiling

Study Overview
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Brief Summary
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The investigators are doing this research study to compare the pharmacokinetics (PK) (rate of absorption) of insulin lispro (Humalog), insulin aspart (Novolog), and insulin glulisine (Apidra) within individual subjects. Additionally, the investigators will perform a preliminary feasibility evaluation of a minimally invasive continuous insulin monitoring (CIM) device and its use to derive PK parameters in human subjects.

Official Title
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Selecting Insulin Analogs for Closed-Loop Control Using Multiplex Pharmacokinetic Profiling

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Other: Multiplex pharmacokinetic profiling
* Other: Continuous insulin monitoring


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older with clinical type 1 diabetes for at least five years Diabetes managed using an insulin infusion pump and rapid- or very-rapid-acting insulins including insulin aspart (NovoLog), insulin lispro (Humalog), and insulin glulisine (Apidra). Ability to consume a sufficient amount of carbohydrates over 2-3 hours to cover 9 units of rapid acting insulin Exclusion Criteria: Unable to provide informed consent Unable to comply with study procedures Inadequate venous access as determined by study nurse or physician at time of screening. Pregnancy History of gastric banding, gastric bypass, or other gastrointestinal condition that may prevent a subject from consuming a normal sized meal Hemoglobin <13.5 for men, < 12 for women

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: All subjects participated in the single arm of the study. Some subjects participated in the continuous insulin monitoring sub-study in addition to the main protocol, or separate from the main protocol.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Multiplex pharmacokinetic profiling<br>Multiplex pharmacokinetic profiling of regular human insulin, insulin aspart, insulin lispro, insulin glulisine, and regular human insulin. All subjects participated in the single study arm and received injections of each type of insulin. Blood samples were drawn at intervals for pharmacokinetic profiling. | Other: Multiplex pharmacokinetic profiling<br> <br> |
| Experimental: Continuous insulin monitoring<br>Continuous insulin monitoring (CIM) of insulin lispro. Some subjects participated in the CIM sub-study, which is distinct from the Multiplex Pharmacokinetic Profiling study. This intervention involved administering insulin lispro and monitoring pharmacokinetic profile of the drug using blood samples and an investigational continuous insulin monitoring system. | Other: Continuous insulin monitoring<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| For Multiplex PK Profiling: Aggregate Mean Difference in Tmax Between the Analog With Greatest and the Analog With the Least Value of Tmax for Individuals | The average difference in tmax between lispro and aspart in all participants | 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes after dose | 
| For Continuous Insulin Monitoring: Time to Maximum Plasma Insulin and Time to Maximum Continuous Insulin Monitoring Insulin |  | 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes after dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Multiplex PK: Average Baseline HbA1c Categorized According to Baseline Use of Insulin Analog Found to Have the Most Favorable PK Profile for Each Individual | Subjects with a difference in tmax between analogs will be categorized as follows: using insulin with best PK for them, using insulin with worst PK for them, or using insulin with intermediate PK for them. The average A1c for each of the three categories is reported. | Baseline | 
| Multiplex PK: Count of Subjects With Difference in Tmax Between the Analog With Greatest and the Analog With the Least Value of Tmax That is > 25% |  | 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes after dose | 
| Multiplex PK: Average Baseline HbA1c Categorized According to Baseline Use of Insulin Analog With Tmax < 60 Minutes vs. Use of an Insulin Analog With Tmax > 60 Minutes for Each Individual | Subjects with a difference in tmax between analogs will be categorized as follows: using insulin with tmax less than or equal to 60 minutes or using insulin with tmax > 60 minutes. The average A1c per group is reported. | Baseline | 
| Multiplex PK: Average Number of Hypoglycemia Events Over the Last Month at Baseline Categorized According to Baseline Use of Insulin Analog Found to Have the Most Favorable PK Profile for Each Individual | Subjects with a difference in tmax between analogs will be categorized as follows: using insulin with best PK for them, using insulin with worst PK for them, or using insulin with intermediate PK for them. The average number of hypoglycemic events per month per group is reported. | 1 month prior to study entry | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics