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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Yale University
ClinicalTrials.gov Identifier:
NCT00652288
First received: March 27, 2008
Last updated: August 30, 2016
Last verified: August 2016
  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 Phase
Diabetes Mellitus, Type I
Drug: Insulin analogs (Lispro and Aspart)
Drug: Insulin analogs (Aspart and Detemir)
Drug: Insulin analogs (Lispro and Glargine)
Phase 1

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 ]

Enrollment: 36
Study Start Date: April 2007
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Catheter day 4
Adolescents with type 1 diabetes with catheters day #4
Drug: Insulin analogs (Lispro and Aspart)
Insulin bolus given through insulin pump
Other Name: Humalog, Novolog
Active Comparator: Catheter day 1
Adolescents with type 1 diabetes with catheter day #1
Drug: Insulin analogs (Lispro and Aspart)
Insulin bolus given through insulin pump
Other Name: Humalog, Novolog
Active Comparator: Aspart and Detemir
Adolescents with type 1 diabetes
Drug: Insulin analogs (Aspart and Detemir)
Drugs given separately
Drug: Insulin analogs (Aspart and Detemir)
Drugs given in the same injection
Active Comparator: Lispro and Glargine
Adolescents with type 1 diabetes
Drug: Insulin analogs (Lispro and Glargine)
Drugs given separately
Drug: Insulin analogs (Lispro and Glargine)
Drugs given in single injection

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

Ages Eligible for Study:   8 Years to 17 Years   (Child)
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Principal Investigator: Eda Cengiz, MD Yale University
  More Information

Publications:
Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT00652288     History of Changes
Other Study ID Numbers: 403026582  JDRF Hypoglycemia Grant 
Study First Received: March 27, 2008
Last Updated: August 30, 2016
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, Globin Zinc
Insulin
Insulin Lispro
Insulin Glargine
Insulin, Short-Acting
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 30, 2016