Septic ShockPhase 1/2PEPSNCT01573806
Pharmacology of Exenatide in Pediatric Sepsis
A Phase 1/2 study testing Exenatide in people with Septic Shock and Inflammation, run by Seattle Children's Hospital at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 1 month to 18 years
- Conditions the study is for
- Septic Shock, Inflammation, Glucose Homeostasis
- What is being tested?
- Exenatide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2012to Oct 2014
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Seattle Children's Hospital
Seattle, Washington, 98105
About this study
Official title: 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.
Read the 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.
- Conditions
- Septic Shock, Inflammation, Glucose Homeostasis, Organ Dysfunction, Health-related Quality of Life
- Being tested
- Exenatide, Exenatide vehicle
- Keywords
- sepsis, septic shock, children, incretins, exenatide, pharmacokinetics, pharmacodynamics, glucose homeostasis, inflammation, cytokines, health-related quality of life, functional status
- Medical subject headings
- Shock, Septic, Inflammation, Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ExenatideDrug
Exenatide, dosed subcutaneously every 12 hours for 4 doses
Exenatide vehicleDrug
Exenatide vehicle, dosed subcutaneously every 12 hours for 4 doses
| Study group | Role | What they receive |
|---|---|---|
| Exenatide | Active comparator | Subjects dosed with exenatide in Phase 2 Receives: Drug: Exenatide |
| Exenatide vehicle | Placebo comparator | Subjects dosed with exenatide vehicle in Phase 2 Receives: Drug: Exenatide vehicle |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 48 hours following the first exenatide dose
Secondary outcomes (8)
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).
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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)
Measured: 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
Measured: 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
Measured: 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)
Measured: 2 measurements: baseline and PICU discharge, the latter occuring on average at 7.5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2012 (estimated)
- Study startOct 2012
- Primary completionOct 2014 (estimated)
- Study completionOct 2014 (estimated)
Why it stopped: No funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Septic ShockStudies of the same condition, open and under way.
- More trials run by Seattle Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seattle Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jerry Zimmerman, Seattle Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01573806
- Sponsor's protocol ID
- PEPS-SCH-001
- Acronym
- PEPS
- Status last verified
- Oct 2017
- First submitted
- 28 Mar 2012
- Last updated
- 5 Oct 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 20215542Mecott 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.
PubMed 20701787Malloy 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.
PubMed 19446153Deane 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.
PubMed 20228679
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1-2 Study of the Pharmacology of Exenatide in Pediatric Sepsis
- ClinicalTrials.gov ID
- NCT01573806
- Acronym / sponsor ID
- PEPS / PEPS-SCH-001
- Conditions
- Septic Shock, Inflammation, Glucose Homeostasis, Organ Dysfunction, Health-related Quality of Life
- Keywords
- sepsis, septic shock, children, incretins, exenatide, pharmacokinetics, pharmacodynamics, glucose homeostasis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Seattle Children's HospitalUniversity, hospital or other
- Study start
- Oct 2012
- Primary completion
- Oct 2014 (estimated)
- Study completion
- Oct 2014 (estimated)
- First posted
- 10 Apr 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Exenatide | Active comparator | Drug: ExenatideSubjects dosed with exenatide in Phase 2 |
| Exenatide vehicle | Placebo comparator | Drug: Exenatide vehicleSubjects dosed with exenatide vehicle in Phase 2 |
Who may qualify
- Ages
- 1 month to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ExenatideExenatide, dosed subcutaneously every 12 hours for 4 doses | Drug | Exenatide |
| Exenatide vehicleExenatide vehicle, dosed subcutaneously every 12 hours for 4 doses | Drug | Exenatide vehicle |
Primary outcome
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.
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.
8 secondary outcomes
Exenatide pharmacodynamics: Effect of exenatide on glucose homeostasis
Time frame: 60 hours following first exenatide dose
Exenatide pharmacodynamics: Effect of exenatide on 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.
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.
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.
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
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.
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
Time frame: 2 measurements: baseline and PICU discharge, the latter occuring on average at 7.5 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2017.
- Background: PubMed 20215542Ivy 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.
- Background: PubMed 20701787Mecott 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.
- Background: PubMed 19446153Malloy 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.
- Background: PubMed 20228679Deane 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.
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Sepsis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Exenatide in people with Septic Shock and Inflammation, run by Seattle Children's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 5 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Exenatide associated adverse event occurence (time frame: From PICU admission to PICU discharge, an average interval of 7.5 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01573806, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2017.