A Phase 1/2 interventional study of Exenatide and Exenatide vehicle in Septic Shock, Inflammation and Glucose Homeostasis, sponsored by Seattle Children's Hospital. Withdrawn at 1 site in United States. Open to participants aged 1 Month to 18 Years. Per ClinicalTrials.gov, last updated 2017-10-05.
Sponsored by Seattle Children's Hospital · Phase 1/2, Interventional, and Treatment
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.
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.
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Exclusion Criteria:
Subjects dosed with exenatide in Phase 2
Drug: Exenatide
Subjects dosed with exenatide vehicle in Phase 2
Drug: Exenatide vehicle
Exenatide, dosed subcutaneously every 12 hours for 4 doses
Exenatide vehicle, dosed subcutaneously every 12 hours for 4 doses
Exenatide associated adverse event occurence
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.
Time frame: 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.
Delineation of the pharmacokinetics of subcutaneously dosed exenatide among children with de novo septic shock.
Time frame: 48 hours following the first exenatide dose
Exenatide pharmacodynamics: Effect of exenatide on glucose homeostasis
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).
Time frame: 60 hours following first exenatide dose
Exenatide pharmacodynamics: Effect of exenatide on serum inflammatory cytokine concentrations.
Delineation of exenatide pharmacodynamics among children with de novo septic shock: AUC of serial serum inflammatory cytokine concentrations.
Time frame: 60 hours following first exenatide dose
Exenatide clinical efficacy: Effect of exenatide on intensity and duration of organ dysfunctions.
AUC of daily Pediatric Logistic Organ Dysfunction (PELOD) scores while the subject remains in the PICU
Time frame: 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.
AUC of daily Vasoactive-Inotropic Scores while the subject remains on vasoactive-inotropic support.
Time frame: 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.
AUC of daily Saturation Indices (\[FiO2\*MAP\]/SpO2)
Time frame: 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
AUC of daily RIFLE criteria
Time frame: 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.
Determination per parent report of declination from baseline to PICU discharge of, Pediatric Overall Performance Category Score and Functional Status Score
Time frame: 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
Determination per parent report of declination from baseline to PICU discharge of, Pediatric Quality of Life Inventory, Generic Core Scales, 4.0 (PedsQL)
Time frame: 2 measurements: baseline and PICU discharge, the latter occuring on average at 7.5 days
This study is withdrawn, as verified in Oct 2017. You cannot join it, but the record below documents what was studied.
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Seattle Children's Hospital