Safety and Dose Escalation Study of Zinc Supplementation in Critically Ill Children

NCT ID: NCT01062009

Last Updated: 2019-08-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-11-30
• Study Completion Date: 2014-11-30

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

Conditions

Critical Illness

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Control group

No intervention

Group Type: NO_INTERVENTION

No interventions assigned to this group

Low dose group

250 mcg/kg/day supplemental IV zinc sulfate divided every 8 hours for 7 days

Group Type: ACTIVE_COMPARATOR

Zinc sulfate

Intervention Type: DRUG

Zinc sulfate 200 mcg/ml in Normal Saline

Medium dose group

500 mcg/kg/day supplemental IV zinc sulfate q8 hours for 7 days

Group Type: ACTIVE_COMPARATOR

Zinc sulfate

Intervention Type: DRUG

Zinc sulfate 200 mcg/ml in Normal Saline

High dose group

750 mcg/kg/day supplemental IV zinc sulfate q8 hrs for 7 days

Group Type: ACTIVE_COMPARATOR

Zinc sulfate

Intervention Type: DRUG

Zinc sulfate 200 mcg/ml in Normal Saline

Interventions

Zinc sulfate

Zinc sulfate 200 mcg/ml in Normal Saline

Intervention Type: DRUG

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

• Minimum Eligible Age: 30 Days
• Maximum Eligible Age: 10 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Hospital Medical Center, Cincinnati

OTHER

Sponsor Role: collaborator

UCSF Benioff Children's Hospital Oakland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Natalie Z Cvijanovich, MD

Role: PRINCIPAL_INVESTIGATOR

UCSF Benioff Children's Hospital Oakland

Locations

Childrens' Hospital & Research Center Oakland

Oakland, California, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 19057435 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17374846 (View on PubMed)

Other Identifiers

SPID 0876

Identifier Type: -

Identifier Source: org_study_id