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)”

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

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Active Control, Parallel Assignment, Pharmacokinetics/Dynamics Study

Study Primary Completion Date: April 2010

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 insulin when it is used in a basal-bolus regimen with insulin Detemir, a new basal insulin analog, 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 concentration, and the peak glucose infusion rate required to maintain euglycemia (GIRMAX) and area under the curve (GIRAUC) of the Aspart bolus, will be similar when the Aspart is combined in the same syringe with the insulin Detemir, compared to when the Aspart and Detemir are given as two separate injections.

Intervention(s) in this Clinical Trial

• Drug: Insulin analogs (Lispro and Aspart)
  • Insulin bolus given through insulin pump

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Catheter day #4
• Active Comparator: 2
  • Catheter day #1

Primary Measures

• Maximum Glucose Infusion Rate (GIR) to maintain euglycemia
  • Time Frame: Six hour observation period
    Safety Issue?: No

Secondary Measures

• Time to Maximum Glucose Infusion Rate
  • Time Frame: Six Hour Observation period
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 8 Years

Maximum Age for this Clinical Trial: 17 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Yale University

Overall Clinical Trial Officials and Contacts

Stuart A Weinzimer, MD Principal Investigator Yale University  

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00652288

Study ID Number: 403026582

ClinicalTrials.gov Identifier: NCT00652288

Health Authority: United States: Institutional Review Board