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

Critical Illness Clinical Trial

Official title:

A Safety and Dose-escalation Study of Zinc Supplementation in Pediatric Critical Illness

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01062009
• Other study ID #: SPID 0876
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: November 2008
• Est. completion date: November 2014

Study information

• Verified date: August 2019
• Source: UCSF Benioff Children’s Hospital Oakland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: November 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 10 Years

Eligibility

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

Related Conditions & MeSH terms

• Critical Illness

Intervention

Drug:
• Zinc sulfate
Zinc sulfate 200 mcg/ml in Normal Saline

Locations

Country	Name	City	State
United States	Childrens' Hospital & Research Center Oakland	Oakland	California

Sponsors (2)

Lead Sponsor	Collaborator
UCSF Benioff Children’s Hospital Oakland	Children's Hospital Medical Center, Cincinnati

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View 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. Epub 2007 Mar 20. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma Zinc Concentration Over Time	Plasma Zinc levels were measured daily during the seven day study period in each group.	7 days
Primary	New Fever	Because of reports of fever in patients wiht zinc overdoses, we monitored patients for new fever while on supplementation	7 days
Secondary	Glucose Homeostasis	Patients were assigned a score based on glucose range to take into account the degree of hyperglycemia as well as the need for insulin over the course of the 7 day study period. This score is an ordinal scale ranging from 1 to 5, with a score of 1 indicating no hyperglycemia, and 5 indicating severe hyperglycemia despite insulin administration.	7 days