Pharmacology of Exenatide in Pediatric Sepsis (PEPS)

This study has been withdrawn prior to enrollment.
(No funding)
Sponsor:
Information provided by (Responsible Party):
Jerry Zimmerman, Seattle Children's Hospital
ClinicalTrials.gov Identifier:
NCT01573806
First received: March 28, 2012
Last updated: May 24, 2013
Last verified: May 2013
  Purpose

Pharmacology of Exenatide in Pediatric Sepsis, PEPS is a phase 1-2 research study that will examine drug safety, drug metabolism, drug action and preliminary drug clinical effects of four does of exenatide injected every 12 hours to children with shock from infection (septic shock). The investigators hypothesize that exenatide can be safely dosed to children with sepsis to achieve blood levels of drug similar to that achieved in teenagers with type 2 diabetes. The investigators further hypothesize that injection of exenatide to children with septic shock will normalize blood glucose levels and decrease levels of inflammation proteins in the blood during the early course of sepsis.


Condition Intervention Phase
Septic Shock
Inflammation
Glucose Homeostasis
Organ Dysfunction
Health-related Quality of Life
Drug: Exenatide
Drug: Exenatide vehicle
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase 1-2 Study of the Pharmacology of Exenatide in Pediatric Sepsis

Resource links provided by NLM:


Further study details as provided by Seattle Children's Hospital:

Primary Outcome Measures:
  • Exenatide associated adverse event occurence [ Time Frame: From PICU admission to PICU discharge, an average interval of 7.5 days ] [ Designated as safety issue: Yes ]
    Potential adverse events associated with exenatide: nausea, abdominal pain, hypoglycemia, delayed gastric emptying, pancreatitis, renal dysfunction, reactions at injection site. Adverse event occurence will be tabulated while the subject remains in the PICU.

  • Exenatide pharmacokinetics: Area under the exenatide concentration curve for 4 subcutaneous exenatide injections administered every 12 hours. [ Time Frame: 48 hours following the first exenatide dose ] [ Designated as safety issue: Yes ]
    Delineation of the pharmacokinetics of subcutaneously dosed exenatide among children with de novo septic shock.


Secondary Outcome Measures:
  • Exenatide pharmacodynamics: Effect of exenatide on glucose homeostasis [ Time Frame: 60 hours following first exenatide dose ] [ Designated as safety issue: Yes ]
    Delineation of exenatide pharmacodynamics among children with de novo septic shock: AUC of all serum glucose values or results of continuous glucose monitoring obtained during the 60 hours following the first dose of exenatide (or drug vehicle).

  • Exenatide pharmacodynamics: Effect of exenatide on serum inflammatory cytokine concentrations. [ Time Frame: 60 hours following first exenatide dose ] [ Designated as safety issue: No ]
    Delineation of exenatide pharmacodynamics among children with de novo septic shock: AUC of serial serum inflammatory cytokine concentrations.

  • Exenatide clinical efficacy: Effect of exenatide on intensity and duration of organ dysfunctions. [ Time Frame: From PICU admission to PICU discharge, an average interval of 7.5 days ] [ Designated as safety issue: No ]
    AUC of daily Pediatric Logistic Organ Dysfunction (PELOD) scores while the subject remains in the PICU

  • Exenatide clinical efficacy: Effect of exenatide on intensity and duration of hemodynamic instability. [ Time Frame: From onset to discontinuation of vasoactive-inotropic support, an average interval of 4 days ] [ Designated as safety issue: No ]
    AUC of daily Vasoactive-Inotropic Scores while the subject remains on vasoactive-inotropic support.

  • Exenatide clinical efficacy: Effect of exenatide on intensity and duration of pulmonary failure. [ Time Frame: From onset to discontinuation of mechanical ventilator support, an average interval of 4.5 days ] [ Designated as safety issue: No ]
    AUC of daily Saturation Indices ([FiO2*MAP]/SpO2)

  • Exenatide clinical efficacy: Effect of exenatide on intensity and duration of renal failure [ Time Frame: From PICU admission to PICU discharge, an average interval of 7.5 days ] [ Designated as safety issue: No ]
    AUC of daily RIFLE criteria

  • Exenatide clinical efficacy: Effect of exenatide on magnitude of sepsis-associated change in functional status. [ Time Frame: 2 measurements: baseline and PICU discharge, the latter occuring on average at 7.5 days ] [ Designated as safety issue: No ]
    Determination per parent report of declination from baseline to PICU discharge of, Pediatric Overall Performance Category Score and Functional Status Score

  • Exenatide clinical efficacy: Effect of exenatide on magnitude of sepsis-associated change in health-related quality of life [ Time Frame: 2 measurements: baseline and PICU discharge, the latter occuring on average at 7.5 days ] [ Designated as safety issue: No ]
    Determination per parent report of declination from baseline to PICU discharge of, Pediatric Quality of Life Inventory, Generic Core Scales, 4.0 (PedsQL)


Enrollment: 0
Study Start Date: October 2012
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Exenatide
Subjects dosed with exenatide in Phase 2
Drug: Exenatide
Exenatide, dosed subcutaneously every 12 hours for 4 doses
Placebo Comparator: Exenatide vehicle
Subjects dosed with exenatide vehicle in Phase 2
Drug: Exenatide vehicle
Exenatide vehicle, dosed subcutaneously every 12 hours for 4 doses

Detailed Description:

Pharmacology of Exenatide in Pediatric Sepsis, PEPS is a phase 1-2 investigation that will examine safety, pharmacokinetics, pharmacodynamics, and preliminary clinical efficacy of 4 subcutaneous doses of exenatide administered every 12 hours to children with newly diagnosed septic shock. The investigators' long term goal is to explore the potential benefit of exenatide on: early immunomodulation and glucose homeostasis, organ dysfunction, and clinically meaningful outcomes associated with pediatric sepsis. The current study objectives are to conduct a "3+3" dose escalation study, and then examine a "best exenatide allometric dose" to generate safety, pharmacokinetic, pharmacodynamic, and initial efficacy data in a larger cohort. In Phase 1 (three allometric doses; three age strata)the investigators will identify an exenatide dosing regimen that mimics area under the exenatide concentration curve for exenatide dosing among adolescents with type 2 diabetes with minimal or no adverse events. A total of 18 subjects are expected to be enrolled in Phase 1. In Phase 2 the investigators will utilize this "best exenatide allometric dose" to further clarify exenatide safety (adverse event occurence: e.g. nausea, abdominal pain, delayed gastric emptying, hypoglycemia, pancreatitis, renal dysfunction), pharmacokinetics, pharmacodynamics (glucose homeostasis; inflammatory cytokine serum concentrations), and effect on clinical outcomes (AUC of Saturation Index, AUC Vasoactive-Inotropic Score, AUC RIFLE Criteria, Pediatric Logistic Organ Dysfunction Score; changes in health-related quality of life and functional status). In Phase 2, 30 subjects in each age strata in the ratio of 4:1, exenatide: vehicle, are expected to be enrolled.

  Eligibility

Ages Eligible for Study:   1 Month to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 44 weeks estimated gestational age to 18 years AND
  • Admitted to the PICU for the sepsis event AND
  • Vascular catheter capable of providing serial blood samples in place AND
  • Diagnosis of septic shock = sepsis with cardiovascular organ dysfunction AND
  • Parents speak English or Spanish

Exclusion Criteria:

  • Greater than 12 hours from admission to PICU to enrollment OR
  • Chronic or acute dialytic therapy, history of renal impairment or renal transplantation OR
  • History of pancreatitis OR
  • History of hypersensitivity to Byetta OR
  • History of severe gastrointestinal disease or gastroparesis OR
  • History of diabetes mellitus, type I or type II OR
  • History of insulin, sulfonyl urea drugs, or coumarin use OR
  • History of hypoglycemia OR
  • History of active pregnancy (effect of exenatide on the fetus is unknown) OR
  • Inability to collect serial blood samples OR
  • Previously enrolled in the PEPS study OR
  • Lack of commitment to aggressive sepsis therapy OR
  • Expectation to succumb from the sepsis event OR
  • Patient is a foster child and/or ward of the state OR
  • Sepsis event associated with a PICU-acquired nosocomial infection OR
  • Patient is enrolled in another interventional investigation that might obscure the potential effects of exenatide dosing.
  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: NCT01573806

Locations
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
Sponsors and Collaborators
Seattle Children's Hospital
  More Information

Publications:
Responsible Party: Jerry Zimmerman, Principal Investigator, Seattle Children's Hospital
ClinicalTrials.gov Identifier: NCT01573806     History of Changes
Other Study ID Numbers: PEPS-SCH-001
Study First Received: March 28, 2012
Last Updated: May 24, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Seattle Children's Hospital:
sepsis
septic shock
children
incretins
exenatide
pharmacokinetics
pharmacodynamics
glucose homeostasis
inflammation
cytokines
health-related quality of life
functional status

Additional relevant MeSH terms:
Inflammation
Shock, Septic
Infection
Pathologic Processes
Sepsis
Shock
Systemic Inflammatory Response Syndrome
Exenatide
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Hypoglycemic Agents
Incretins
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 29, 2014