Critical IllnessPhase 1/2NCT01062009
Safety and Dose Escalation Study of Zinc Supplementation in Critically Ill Children
A Phase 1/2 study testing Zinc sulfate in people with Critical Illness, run by UCSF Benioff Children's Hospital Oakland at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 30 days to 10 years
- Conditions the study is for
- Critical Illness
- What is being tested?
- Zinc sulfate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2008to Nov 2014
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 30 days to 10 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Childrens' Hospital & Research Center Oakland
Oakland, California, 94611
About this study
Official title: A Safety and Dose-escalation Study of Zinc Supplementation in Pediatric Critical Illness
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.
Read the 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
- Being tested
- Zinc sulfate
- Medical subject headings
- Critical Illness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zinc sulfateDrug
Zinc sulfate 200 mcg/ml in Normal Saline
| Study group | Role | What they receive |
|---|---|---|
| Control group | No intervention | No intervention |
| Low dose group | Active comparator | 250 mcg/kg/day supplemental IV zinc sulfate divided every 8 hours for 7 days Receives: Drug: Zinc sulfate |
| Medium dose group | Active comparator | 500 mcg/kg/day supplemental IV zinc sulfate q8 hours for 7 days Receives: Drug: Zinc sulfate |
| High dose group | Active comparator | 750 mcg/kg/day supplemental IV zinc sulfate q8 hrs for 7 days Receives: Drug: Zinc sulfate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma Zinc Concentration Over Time
Plasma Zinc levels were measured daily during the seven day study period in each group.
Measured: 7 days
New Fever
Because of reports of fever in patients wiht zinc overdoses, we monitored patients for new fever while on supplementation
Measured: 7 days
Secondary outcomes (1)
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.
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2010 (estimated)
- Study startNov 2008
- Primary completionOct 2014
- Study completionNov 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Critical IllnessStudies of the same condition, open and under way.
- 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
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- UCSF Benioff Children's Hospital Oakland
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Hospital Medical Center, Cincinnati
- Responsible party
- Sponsor
- Investigators
- Natalie Z Cvijanovich, MD, Principal investigator, UCSF Benioff Children's Hospital Oakland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01062009
- Sponsor's protocol ID
- SPID 0876
- Status last verified
- Aug 2019
- First submitted
- 2 Feb 2010
- Last updated
- 20 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 19057435Wong 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.
PubMed 17374846
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Safety and Dose-escalation Study of Zinc Supplementation in Pediatric Critical Illness
- ClinicalTrials.gov ID
- NCT01062009
- Acronym / sponsor ID
- SPID 0876
- Conditions
- Critical Illness
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- UCSF Benioff Children's Hospital OaklandUniversity, hospital or other
- Collaborators
- Children's Hospital Medical Center, Cincinnati
- Study start
- Nov 2008
- Primary completion
- Oct 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 4 Feb 2010 (estimated)
- Results
- Posted 20 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Control group | No intervention | –No intervention |
| Low dose group | Active comparator | Drug: Zinc sulfate250 mcg/kg/day supplemental IV zinc sulfate divided every 8 hours for 7 days |
| Medium dose group | Active comparator | Drug: Zinc sulfate500 mcg/kg/day supplemental IV zinc sulfate q8 hours for 7 days |
| High dose group | Active comparator | Drug: Zinc sulfate750 mcg/kg/day supplemental IV zinc sulfate q8 hrs for 7 days |
Who may qualify
- Ages
- 30 days to 10 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (6 listed)
- 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
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 |
|---|---|---|
| Zinc sulfateZinc sulfate 200 mcg/ml in Normal Saline | Drug | High dose group, Low dose group, Medium dose group |
Primary outcome
Plasma Zinc Concentration Over Time
Time frame: 7 days
Plasma Zinc levels were measured daily during the seven day study period in each group.
New Fever
Time frame: 7 days
Because of reports of fever in patients wiht zinc overdoses, we monitored patients for new fever while on supplementation
1 secondary outcome
Glucose Homeostasis
Time frame: 7 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19057435Cvijanovich 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.
- Background: PubMed 17374846Wong 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.
- Individual participant dataSharing planned: No
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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.
Natalie Z Cvijanovich, MD principal investigator
UCSF Benioff Children's Hospital Oakland
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 Zinc sulfate in people with Critical Illness, run by UCSF Benioff Children's Hospital Oakland 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 6 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: finished, as of the sponsor's last update on 20 Aug 2019. 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. 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?
Yes. Results are posted in the registry (first posted 20 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Plasma Zinc Concentration Over Time (time frame: 7 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 NCT01062009, which also lists 2 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 20 Aug 2019.