Zinc Therapy for Critical Illness

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Vermont

Must not be taking: Zinc supplements

Disqualifiers: Gastrointestinal disease, Anoxic brain injury, AIDS, others

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

55 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether zinc (as zinc sulfate) can improve outcomes for people with severe sepsis, a life-threatening condition often caused by infection that leads to organ failure. Researchers aim to determine the optimal zinc dose and its effects on inflammation and the immune response. They will compare zinc levels between critically ill sepsis patients on mechanical ventilation and healthy volunteers. This study may suit someone with severe sepsis who is on a ventilator. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications, but you cannot participate if you have taken zinc supplements in the past month or are receiving TPN (total parenteral nutrition) with added zinc.

Is there any evidence suggesting that zinc therapy is likely to be safe for humans?

Research has shown that zinc is important for the immune system and overall health. Studies have found that administering zinc intravenously at 500 micrograms per kilogram per day was well-tolerated by patients, with no significant negative side effects at this dose. This treatment also improved blood zinc levels to a healthy range.

For healthy volunteers, similar doses of zinc were also safe. However, general warnings about zinc include potential eye irritation and harm to aquatic life if not handled properly. These concerns do not apply to clinical settings but are important for safe handling.

Overall, evidence suggests that zinc can be safely administered to both patients with sepsis and healthy individuals at the studied doses. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sepsis?

Unlike the standard treatments for severe sepsis, which typically involve antibiotics, fluids, and vasopressors to support blood pressure, zinc sulfate offers a potentially new approach by leveraging zinc's role in immune function and inflammation reduction. Researchers are excited about zinc because it acts as an antioxidant and may help modulate the body's immune response, which is crucial in managing the systemic inflammation seen in sepsis. Additionally, zinc sulfate's intravenous administration allows for precise dosing and rapid onset, which could be beneficial in critically ill patients who need swift intervention.

What evidence suggests that zinc therapy might be an effective treatment for sepsis?

Research has shown that zinc plays a crucial role in supporting the immune system and managing stress in the body. Many people with sepsis, a serious infection, lack sufficient zinc, which can worsen their condition. Animal studies demonstrated that extra zinc improved survival rates in sepsis. However, human studies did not consistently show reduced death rates or shorter ICU stays with zinc supplementation. This trial will compare the effects of zinc supplementation in different groups, including those with severe sepsis and healthy volunteers. Despite mixed results, zinc's role in immune support makes it a promising area for further research in treating sepsis. ^{3 6 7 8 9}

Who Is on the Research Team?

Renee D Stapleton, MD, PhD

Principal Investigator

University of Vermont

Are You a Good Fit for This Trial?

This trial is for adults over 18 who are on mechanical ventilation due to severe sepsis. They shouldn't have taken zinc supplements recently, be pregnant or breastfeeding, have certain chronic diseases like AIDS with low CD4 count, significant kidney issues, or a history of organ transplant.

Inclusion Criteria

You need a machine to help you breathe.

You have a serious case of sepsis.

Exclusion Criteria

You were given zinc supplements during your hospital stay.

You have taken zinc supplements in the last month.

Post-cardiac arrest with significant anoxic brain injury

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous zinc or placebo for a total of 7 days, with dose-finding and pharmacokinetic testing

1 week

Daily visits (in-person) for dosing and monitoring

Pharmacokinetic Testing

Pharmacokinetic testing is performed to compare zinc metabolism in sepsis patients and healthy controls

8 hours for healthy volunteers, ongoing for sepsis patients

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Zinc Sulfate

Trial Overview The study tests different doses of intravenous zinc sulfate in critically ill patients with severe sepsis to find the right dose and see how it affects inflammation and immunity compared to healthy individuals. Patients will receive either zinc or placebo for up to 7 days.

How Is the Trial Designed?

Group I: Zinc in severe sepsis Experimental Treatment 1 Intervention

Mechanically ventilated patients with severe sepsis will be randomized to receive IV zinc or placebo

Group II: Healthy Volunteers receiving zinc Experimental Treatment 1 Intervention

Cohort of healthy volunteers will receive a single dose of 500 mcg/kg IBW IV zinc and pharmacokinetics will be measured for 8 hours. PK in sepsis patients and healthy volunteers will be compared.

Group III: Severe sepsis without zinc Placebo Group 1 Intervention

Mechanically ventilated patients with severe sepsis will be randomized to receive IV zinc or placebo

Who Is Running the Clinical Trial?

University of Vermont

Lead Sponsor

Trials

283

Recruited

3,747,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5609528/

A Safety and Dose-escalation Study of Intravenous Zinc ... Based on pharmacokinetic modeling, the 500 μg/kg/day IV zinc supplementation dose nearly restored levels to within the normal range, without inducing prolonged ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4151581/

Pharmacokinetics and Biodistribution of Zinc-Enriched ... Maximum plasma concentration values were 3.87 and 2.81 μg/mL for ZnY and ZnSO4, respectively. Both ZnY and ZnSO4 were slowly eliminated with a ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S000291652203742X

Zinc absorption as a function of the dose of zinc sulfate in ... Conclusions. Increases in aqueous zinc doses >20 mg result in relatively small and progressively diminishing increases in AZ postabsorptively in healthy adults.

4. link.springer.com link.springer.com/article/10.1007/BF03189977

Pharmacokinetic study of orally administered zinc in humans The absorption and distribution of the essential trace element zinc in humans was investigated in 10 subjects by performing a pharmacokinetic study.

5. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2019/209377Orig1s000MultidisciplineR.pdf

Multi-Discipline Review - accessdata.fda.gov Zinc is an essential trace element (TE) necessary in the diet to maintain health. Zinc Sulfate Injection provides 30 mg/ 10 ml (3 mg/ ml) and 25 ...

6. americanregent.com americanregent.com/media/3037/zinc-sulfate-injection-sds-26oct2020.pdf

Zinc Sulfate / Concentrated Zinc Sulfate Injection, USP Signal Word (GHS-US). : Warning. Hazard Statements (GHS-US). : H319 - Causes serious eye irritation. H402 - Harmful to aquatic life.

7. punchout.medline.com punchout.medline.com/media/catalog/Docs/MSDS/MSD_SDSD722122.pdf

Zinc Sulfate Injection USP Signal Word (GHS-US/CA). : Warning. Hazard Statements (GHS-US/CA). : H319 - Causes serious eye irritation. H401 - Toxic to aquatic life.

8. teck.com teck.com/media/Zinc_Sulphate_Solution_SDS.pdf

ZINC SULPHATE SOLUTION SAFETY DATA SHEET Zinc Sulphate Solution causes serious eye irritation and is very toxic to aquatic life. Wear eye protection, avoid release, and wash skin after ...

9. npic.orst.edu npic.orst.edu/factsheets/znso4gen.html

Zinc Sulfate General Fact Sheet Breathing in zinc sulfate can irritate the respiratory tract, cause nausea, vomiting, stomach ache, dizziness, depression, metallic taste in the mouth, and ...