Clinical trial NCT01062009: Safety and Dose Escalation Study of Zinc Supplementation in Critically Ill Children
Official title: A Safety and Dose-escalation Study of Zinc Supplementation in Pediatric Critical Illness
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Critical Illness
Lead sponsor: UCSF Benioff Children's Hospital Oakland
Sponsor class: OTHER
Collaborators: name: Children's Hospital Medical Center, Cincinnati
First posted: 2010-02-04
Enrollment: 24
Sex: ALL
Minimum age (years): 30
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The purpose of the study is 1) to determine whether administration of intravenous zinc to critically ill children is safe, and 2) to determine an appropriate dose of zinc supplementation.

Detailed description: Our recently published studies in children with septic shock demonstrated that pediatric septic shock is characterized by large scale repression of genes that either directly depend on normal zinc homeostasis or directly participate in zinc homeostasis. Functional validation studies demonstrated that nonsurvivors of pediatric septic shock have abnormally low serum zinc concentrations. A follow-up pilot study in a general population of critically ill children demonstrated that the presence of low plasma zinc concentrations is a prevalent problem in critically ill children. In addition, low plasma zinc concentrations correlate inversely with indices of inflammation and directly with the number of organ failures. These preliminary data, coupled with the expected safety of zinc supplementation, provided the rationale for a double blinded, prospective, placebo-controlled trial of zinc supplementation in critically ill children, with the two primary study endpoints to assess efficacy being highly clinically relevant: reduction of the lymphopenia rate and improvement of glucose homeostasis. Although the proposal was well-received, the primary concern precluding funding of this trial were lack of safety and dosing data for intravenous zinc. We have therefore developed a proposal for a Phase I/II study of safety and pharmacokinetics to address these concerns. It is anticipated that data generated through this proposal will provide the necessary preliminary data to re-submit our application for an interventional efficacy trial of zinc supplementation in critically ill children

Eligibility criteria: Inclusion Criteria:

* Admission to pediatric intensive care unit
* Age between 1 month and 10 years
* Pediatric Risk of Mortality III score \> 5, OR presence of at least 1 new organ failure
* Anticipated pediatric intensive care unit length of stay \> 3 days
* Ability of parent or legal guardian to provide informed consent

Exclusion Criteria:

* Known zinc deficiency
* Pre-existing bone marrow failure
* New or existing diagnosis of diabetes mellitus
* Limitation of care orders in place
* New diagnosis of brain injury, encephalopathy
* Clinical contraindication for zinc supplementation

Primary outcomes:
measure: Plasma Zinc Concentration Over Time
timeFrame: 7 days
measure: New Fever
timeFrame: 7 days
Secondary outcomes:
measure: Glucose Homeostasis
timeFrame: 7 days
Other outcomes:
Locations:
city: Oakland
country: United States
facility: Childrens' Hospital & Research Center Oakland
state: California
Study officials:
affiliation: UCSF Benioff Children's Hospital Oakland
name: Natalie Z Cvijanovich, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cvijanovich NZ, King JC, Flori HR, Gildengorin G, Wong HR. Zinc homeostasis in pediatric critical illness. Pediatr Crit Care Med. 2009 Jan;10(1):29-34. doi: 10.1097/PCC.0b013e31819371ce.
citation: Wong HR, Shanley TP, Sakthivel B, Cvijanovich N, Lin R, Allen GL, Thomas NJ, Doctor A, Kalyanaraman M, Tofil NM, Penfil S, Monaco M, Tagavilla MA, Odoms K, Dunsmore K, Barnes M, Aronow BJ; Genomics of Pediatric SIRS/Septic Shock Investigators. Genome-level expression profiles in pediatric septic shock indicate a role for altered zinc homeostasis in poor outcome. Physiol Genomics. 2007 Jul 18;30(2):146-55. doi: 10.1152/physiolgenomics.00024.2007. Epub 2007 Mar 20.