Clinical trial NCT00652288: Evaluation of Pharmacokinetics and Pharmacodynamic Properties of Rapid-Acting Insulin Analogs
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type I
Keywords: Type I Diabetes Mellitus
Lead sponsor: Yale University
Sponsor class: OTHER
First posted: 2008-04-03
Enrollment: 36
Sex: ALL
Minimum age (years): 8
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Age 8-17 (inclusive), of whom 15 will be prepubertal and 60 pubertal;
2. Clinical diagnosis of T1D (based on clinical presentation, insulin dependence,and/or history of ketosis;
3. Diagnosis of T1D for at least one year's duration;
4. On CSII therapy for at least three months;
5. HbA1c 6.5-8.0%, inclusive;
6. Body mass index \< 95% for age and gender;
7. Meeting minimum weight requirement of at least 17.6 kg (for pre-pubertal subjects) or 34.6 kg (for pubertal subjects)
8. Ability to comprehend written and spoken English

Exclusion Criteria:

1. Any other medical disease aside from T1D or treated hypothyroidism
2. Receiving any other medication besides insulin or levothyroxine
3. Female subjects of reproductive potential who may be pregnant, breast feeding, or not consistently utilizing barrier methods or abstinence as contraception
4. Inability to comprehend written and spoken English
5. 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

Primary outcomes:
measure: Maximum Glucose Infusion Rate (GIR) to maintain euglycemia
timeFrame: Six hour observation period
Secondary outcomes:
measure: Time to Maximum Glucose Infusion Rate
timeFrame: Six Hour Observation period
Other outcomes:
Locations:
Study officials:
affiliation: Yale University
name: Stuart A Weinzimer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Yale University
name: Eda Cengiz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cengiz E, Swan KL, Tamborlane WV, Sherr JL, Martin M, Weinzimer SA. The alteration of aspart insulin pharmacodynamics when mixed with detemir insulin. Diabetes Care. 2012 Apr;35(4):690-2. doi: 10.2337/dc11-0732. Epub 2012 Feb 28.
citation: Cengiz E, Tamborlane WV, Martin-Fredericksen M, Dziura J, Weinzimer SA. Early pharmacokinetic and pharmacodynamic effects of mixing lispro with glargine insulin: results of glucose clamp studies in youth with type 1 diabetes. Diabetes Care. 2010 May;33(5):1009-12. doi: 10.2337/dc09-2118. Epub 2010 Feb 11.
citation: Swan KL, Dziura JD, Steil GM, Voskanyan GR, Sikes KA, Steffen AT, Martin ML, Tamborlane WV, Weinzimer SA. Effect of age of infusion site and type of rapid-acting analog on pharmacodynamic parameters of insulin boluses in youth with type 1 diabetes receiving insulin pump therapy. Diabetes Care. 2009 Feb;32(2):240-4. doi: 10.2337/dc08-0595. Epub 2008 Nov 18.
citation: Swan KL, Weinzimer SA, Dziura JD, Steil GM, Voskanyan GR, Steffen AT, Martin ML, Tamborlane WV. Effect of puberty on the pharmacodynamic and pharmacokinetic properties of insulin pump therapy in youth with type 1 diabetes. Diabetes Care. 2008 Jan;31(1):44-6. doi: 10.2337/dc07-0737. Epub 2007 Oct 1. No abstract available.