Zinc Therapy for Critical Illness
Trial Summary
What is the purpose of this trial?
Sepsis is a clinical syndrome often caused by a bloodstream infection that results in a common set of symptoms termed systemic inflammatory response syndrome (SIRS). Severe sepsis (sepsis with organ failure) is the leading cause of death in critically ill patients in the US. Most patients with severe sepsis need to be treated in the intensive care unit with mechanical ventilation and intravenous antibiotics. Between 30 to 50% of all severe sepsis patients die and quality of life in survivors is substantially reduced. New therapies are needed to improve clinical outcomes in patients with sepsis. A new area of interest in the treatment of critical illness is pharmaconutrition, in which micronutrients (like zinc) are studied and administered to determine if they affect the inflammatory response or immunologic processes in critical illness. The FDA does not regulate micronutrients and does not require rigorous pharmacokinetic (the study of how a drug or nutrient is metabolized in the body) testing so it is not clear how to dose micronutrients in critically ill patients. It is also not clear if critically ill patients would metabolize these micronutrients differently than healthy people and would need different dosing levels. This is true of zinc, the focus of this research study. Zinc is essential for normal immune function, oxidative stress response, and wound healing, and its homeostasis is tightly regulated. Zinc deficiency occurs in \>10% of Americans and leads to loss of innate and adaptive immunity and increased susceptibility to infections. The symptoms of zinc deficiency are similar to many of the symptoms of SIRS and there is strong biologic rationale to suggest that the zinc deficiency seen in nearly all sepsis patients may contribute to the development of sepsis syndrome and to the "immunoparalysis" common in sepsis patients This study has three specific aims, 1) to perform a phase I dose-finding study of intravenous zinc in mechanically ventilated patients with severe sepsis; 2) to define the pharmacokinetic of intravenous zinc in mechanically ventilated patients with severe sepsis compared to healthy controls; and 3) to investigate the impact of zinc on inflammation, immunity, and oxidant defense in patients with severe sepsis. A total of 40 critically ill patients from the FAHC intensive care units and 15 healthy controls will be enrolled in the study. The critically ill patient population will be divided into 4 dosing groups of 10 subjects (7 randomized to zinc and 3 to saline placebo). Group 1 will receive 500mcg/kg IBW/day elemental zinc in divided doses every 8 hours. If the 50th percentile of the normal plasma zinc range (110mcg/dL) has not been achieved in all patients by 7 days and there are no safety concerns, sequential groups of patients will receive increasing doses in 250mcg increments to the ceiling dose. Groups 2 through 4 will receive 750, 1000, and 1250mcg/kgIBW/day elemental zinc, respectively. Each participant will receive the intravenous zinc or placebo for a total of 7 days unless they die or leave the ICU earlier. Pharmacokinetic testing will be obtained from 40 of the critically ill subjects and in 15 healthy controls. Additional blood will be drawn during the infusion protocol to investigate the impact of zinc on inflammation, immunity, and oxidant defense.
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.
What data supports the effectiveness of the drug Zinc Sulfate for critical illness?
Zinc is important for immune function and healing, and in non-critically ill patients, it has improved immune markers. However, in critically ill patients, studies show no significant reduction in mortality or hospital stay with zinc supplementation, indicating more research is needed to confirm its effectiveness.12345
Is zinc therapy safe for humans?
How is zinc sulfate therapy unique for critical illness?
Zinc sulfate therapy for critical illness is unique because it can be administered intravenously, which allows for faster increases in zinc levels compared to oral administration. This method may be particularly beneficial for critically ill patients who have difficulty absorbing nutrients through the digestive system.1691011
Research Team
Renee D Stapleton, MD, PhD
Principal Investigator
University of Vermont
Eligibility Criteria
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
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive intravenous zinc or placebo for a total of 7 days, with dose-finding and pharmacokinetic testing
Pharmacokinetic Testing
Pharmacokinetic testing is performed to compare zinc metabolism in sepsis patients and healthy controls
Follow-up
Participants are monitored for safety and effectiveness after treatment
Treatment Details
Interventions
- Zinc Sulfate
Find a Clinic Near You
Who Is Running the Clinical Trial?
University of Vermont
Lead Sponsor
National Heart, Lung, and Blood Institute (NHLBI)
Collaborator