Pharmacology of Exenatide in Pediatric Sepsis
| Status: | Withdrawn |
|---|---|
| Conditions: | Hospital, Endocrine |
| Therapuetic Areas: | Endocrinology, Other |
| Healthy: | No |
| Age Range: | Any - 18 |
| Updated: | 10/7/2017 |
| Start Date: | October 2012 |
| End Date: | October 2014 |
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.
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.
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.
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.
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