Pharmacology of Exenatide in Pediatric Sepsis

NCT01573806 | Withdrawn Phase 1 DMC

• 1 other identifier: PEPS-SCH-001
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Septic Shock; Inflammation; Glucose Homeostasis; Organ Dysfunction; Health-related Quality of Life

Keywords

sepsis; septic shock; children; incretins; exenatide; pharmacokinetics; pharmacodynamics; glucose homeostasis; inflammation; cytokines; health-related quality of life; functional status

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  48 hours following the first exenatide dose

Secondary Outcomes (8)

• Exenatide pharmacodynamics: Effect of exenatide on glucose homeostasis

  60 hours following first exenatide dose

• Exenatide pharmacodynamics: Effect of exenatide on serum inflammatory cytokine concentrations.

  60 hours following first exenatide dose

• Exenatide clinical efficacy: Effect of exenatide on intensity and duration of organ dysfunctions.

  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.

  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.

  From onset to discontinuation of mechanical ventilator support, an average interval of 4.5 days

Study Arms (2)

Exenatide

ACTIVE COMPARATOR

Subjects dosed with exenatide in Phase 2

Drug: Exenatide

Exenatide vehicle

PLACEBO COMPARATOR

Subjects dosed with exenatide vehicle in Phase 2

Drug: Exenatide vehicle

Interventions

Exenatide DRUG

Exenatide, dosed subcutaneously every 12 hours for 4 doses

Exenatide

Exenatide vehicle DRUG

Exenatide vehicle, dosed subcutaneously every 12 hours for 4 doses

Exenatide vehicle

Eligibility Criteria

• Age: 1 Month - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Seattle Children's Hospital: lead

Study Sites (1)

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Related Publications (4)

• Ivy SP, Siu LL, Garrett-Mayer E, Rubinstein L. Approaches to phase 1 clinical trial design focused on safety, efficiency, and selected patient populations: a report from the clinical trial design task force of the national cancer institute investigational drug steering committee. Clin Cancer Res. 2010 Mar 15;16(6):1726-36. doi: 10.1158/1078-0432.CCR-09-1961. Epub 2010 Mar 9.

  PMID: 20215542 BACKGROUND

• Mecott GA, Herndon DN, Kulp GA, Brooks NC, Al-Mousawi AM, Kraft R, Rivero HG, Williams FN, Branski LK, Jeschke MG. The use of exenatide in severely burned pediatric patients. Crit Care. 2010;14(4):R153. doi: 10.1186/cc9222. Epub 2010 Aug 11.

  PMID: 20701787 BACKGROUND

• Malloy J, Capparelli E, Gottschalk M, Guan X, Kothare P, Fineman M. Pharmacology and tolerability of a single dose of exenatide in adolescent patients with type 2 diabetes mellitus being treated with metformin: a randomized, placebo-controlled, single-blind, dose-escalation, crossover study. Clin Ther. 2009 Apr;31(4):806-15. doi: 10.1016/j.clinthera.2009.04.005.

  PMID: 19446153 BACKGROUND

• Deane AM, Chapman MJ, Fraser RJ, Summers MJ, Zaknic AV, Storey JP, Jones KL, Rayner CK, Horowitz M. Effects of exogenous glucagon-like peptide-1 on gastric emptying and glucose absorption in the critically ill: relationship to glycemia. Crit Care Med. 2010 May;38(5):1261-9. doi: 10.1097/CCM.0b013e3181d9d87a.

  PMID: 20228679 BACKGROUND

MeSH Terms

Conditions

Shock, Septic; Inflammation; Sepsis

Interventions

Exenatide

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 28, 2012
• First Posted: April 10, 2012
• Study Start: October 1, 2012
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: October 5, 2017

Record last verified: 2017-10

Locations

US (1)