Evaluation of Pharmacokinetics and Pharmacodynamic Properties of Rapid-Acting Insulin Analogs (PK/PD)

This study is enrolling participants by invitation only.
Sponsor:
Information provided by:
Yale University
ClinicalTrials.gov Identifier:
NCT00652288
First received: March 27, 2008
Last updated: March 31, 2008
Last verified: March 2008
  Purpose

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

Condition Intervention
Diabetes Mellitus, Type I
Drug: Insulin analogs (Lispro and Aspart)

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Maximum Glucose Infusion Rate (GIR) to maintain euglycemia [ Time Frame: Six hour observation period ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to Maximum Glucose Infusion Rate [ Time Frame: Six Hour Observation period ] [ Designated as safety issue: No ]

Estimated Enrollment: 75
Study Start Date: April 2007
Estimated Study Completion Date: January 2012
Estimated Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Catheter day #4
Drug: Insulin analogs (Lispro and Aspart)
Insulin bolus given through insulin pump
Other Name: Humalog, Novolog
Active Comparator: 2
Catheter day #1
Drug: Insulin analogs (Lispro and Aspart)
Insulin bolus given through insulin pump
Other Name: Humalog, Novolog

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 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.

  Eligibility

Ages Eligible for Study:   8 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00652288

Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Stuart A Weinzimer, MD Yale University
  More Information

No publications provided

Responsible Party: Stuart Weinzimer, MD, Yale University School of Medicine
ClinicalTrials.gov Identifier: NCT00652288     History of Changes
Other Study ID Numbers: 403026582, JDRF Hypoglycemia Grant
Study First Received: March 27, 2008
Last Updated: March 31, 2008
Health Authority: United States: Institutional Review Board

Keywords provided by Yale University:
Type I Diabetes Mellitus

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014