Pharmacology of Exenatide in Pediatric Sepsis (PEPS)

October 3, 2017 updated by: Jerry Zimmerman, Seattle Children's Hospital

Phase 1-2 Study of the Pharmacology of Exenatide in Pediatric Sepsis

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98105
        • Seattle Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 month to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Exenatide associated adverse event occurence
Time Frame: From PICU admission to PICU discharge, an average interval of 7.5 days
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.
From PICU admission to PICU discharge, an average interval of 7.5 days
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
Delineation of the pharmacokinetics of subcutaneously dosed exenatide among children with de novo septic shock.
48 hours following the first exenatide dose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Exenatide pharmacodynamics: Effect of exenatide on glucose homeostasis
Time Frame: 60 hours following first exenatide dose
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).
60 hours following first exenatide dose
Exenatide pharmacodynamics: Effect of exenatide on serum inflammatory cytokine concentrations.
Time Frame: 60 hours following first exenatide dose
Delineation of exenatide pharmacodynamics among children with de novo septic shock: AUC of serial serum inflammatory cytokine concentrations.
60 hours following first exenatide dose
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
AUC of daily Pediatric Logistic Organ Dysfunction (PELOD) scores while the subject remains in the PICU
From PICU admission to PICU discharge, an average interval of 7.5 days
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
AUC of daily Vasoactive-Inotropic Scores while the subject remains on vasoactive-inotropic support.
From onset to discontinuation of vasoactive-inotropic support, an average interval of 4 days
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
AUC of daily Saturation Indices ([FiO2*MAP]/SpO2)
From onset to discontinuation of mechanical ventilator support, an average interval of 4.5 days
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
AUC of daily RIFLE criteria
From PICU admission to PICU discharge, an average interval of 7.5 days
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
Determination per parent report of declination from baseline to PICU discharge of, Pediatric Overall Performance Category Score and Functional Status Score
2 measurements: baseline and PICU discharge, the latter occuring on average at 7.5 days
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
Determination per parent report of declination from baseline to PICU discharge of, Pediatric Quality of Life Inventory, Generic Core Scales, 4.0 (PedsQL)
2 measurements: baseline and PICU discharge, the latter occuring on average at 7.5 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Seattle Children's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2012

Primary Completion (Anticipated)

October 1, 2014

Study Completion (Anticipated)

October 1, 2014

Study Registration Dates

First Submitted

March 28, 2012

First Submitted That Met QC Criteria

April 5, 2012

First Posted (Estimate)

April 10, 2012

Study Record Updates

Last Update Posted (Actual)

October 5, 2017

Last Update Submitted That Met QC Criteria

October 3, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PEPS-SCH-001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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