Evaluation of Pharmacokinetics and Pharmacodynamic Properties of Rapid-Acting Insulin Analogs

Study Overview
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Brief Summary
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The aim of this study is to evaluate the variations in pharmacokinetic and pharmacodynamic properties of rapid-acting insulin analogs when given as a bolus by subcutaneous insulin infusion pump as typically encountered in the care of children with type 1 diabetes. The specific factors under investigation are: the effects of puberty type of insulin analog site of catheter insertion and age of catheter

Detailed Description
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The aim of this study is to evaluate the variations in pharmacokinetic (as determined by serum free insulin concentrations) and pharmacodynamic (as determined by the glucose infusion rate required to maintain euglycemia during a euglycemic clamp) properties of the rapid acting insulin analogs when given as a bolus by subcutaneous insulin infusion pump as typically encountered in the care of children with type 1 diabetes. The specific factors we will investigate are the effects of puberty (pre- vs. pubertal), type of insulin analog (lispro or aspart insulin), site of catheter insertion (gluteal vs. abdominal), and age of catheter (fresh insertion vs. three-day duration) Our hypotheses are that the peak (Imax) and area under the curve (IAUC) serum free insulin concentration, and the peak glucose infusion rate required to maintain euglycemia (GIRmax) and area under the curve (GIRAUC) will vary based on these conditions, in children given the same weight-based dose. We will also evaluate the pharmacokinetic and pharmacodynamic properties of Aspart and Lispro insulin when used in a basal-bolus regimen with insulin Detemir or Glargine, new basal insulin analogs, given as separate injections and when combined in a single injection in adolescent patients with Type 1 DM. We hypothesize that the peak (IMAX) and area under the curve (IAUC) serum insulin concentrations, and the peak glucose infusion rate required to maintain euglycemia (GIRMAX) and area under the curve (GIRAUC) of the Aspart/Lispro bolus, will be similar when the Aspart/Lispro is combined in the same syringe with the insulin Detemir/Glargine, compared to when the Aspart/Lispro and Detemir/Glargine are given as two separate injections.

Official Title
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Evaluation of Pharmacokinetic and Pharmacodynamic Properties of Rapid-Acting Insulin Analogs Given as a Bolus by Continuous Subcutaneous Insulin Infusion (CSII) and in MDI Basal-Bolus Therapy in Pediatric Subjects With Type 1 Diabetes (TID)

Conditions
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Diabetes Mellitus, Type I

Intervention / Treatment
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* Drug: Insulin analogs (Lispro and Aspart)
* Drug: Insulin analogs (Aspart and Detemir)
* Drug: Insulin analogs (Aspart and Detemir)
* Drug: Insulin analogs (Lispro and Glargine)
* Drug: Insulin analogs (Lispro and Glargine)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 8-17 (inclusive), of whom 15 will be prepubertal and 60 pubertal; Clinical diagnosis of T1D (based on clinical presentation, insulin dependence,and/or history of ketosis; Diagnosis of T1D for at least one year's duration; On CSII therapy for at least three months; HbA1c 6.5-8.0%, inclusive; Body mass index < 95% for age and gender; Meeting minimum weight requirement of at least 17.6 kg (for pre-pubertal subjects) or 34.6 kg (for pubertal subjects) Ability to comprehend written and spoken English Exclusion Criteria: Any other medical disease aside from T1D or treated hypothyroidism Receiving any other medication besides insulin or levothyroxine Female subjects of reproductive potential who may be pregnant, breast feeding, or not consistently utilizing barrier methods or abstinence as contraception Inability to comprehend written and spoken English Any other condition, which in the judgement of the investigators, would interfere with the subject's or parents' ability to provide informed consent or the investigator's ability to perform the study

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 17 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Catheter day 4<br>Adolescents with type 1 diabetes with catheters day #4 | Drug: Insulin analogs (Lispro and Aspart)<br>* Insulin bolus given through insulin pump<br>* Other names: Humalog, Novolog;|
| Active Comparator: Catheter day 1<br>Adolescents with type 1 diabetes with catheter day #1 | Drug: Insulin analogs (Lispro and Aspart)<br>* Insulin bolus given through insulin pump<br>* Other names: Humalog, Novolog;|
| Active Comparator: Aspart and Detemir<br>Adolescents with type 1 diabetes | Drug: Insulin analogs (Aspart and Detemir)<br>* Drugs given separately<br>Drug: Insulin analogs (Aspart and Detemir)<br>* Drugs given in the same injection<br>|
| Active Comparator: Lispro and Glargine<br>Adolescents with type 1 diabetes | Drug: Insulin analogs (Lispro and Glargine)<br>* Drugs given separately<br>Drug: Insulin analogs (Lispro and Glargine)<br>* Drugs given in single injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Glucose Infusion Rate (GIR) to maintain euglycemia |  | Six hour observation period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Maximum Glucose Infusion Rate |  | Six Hour Observation period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type I Diabetes Mellitus