Curcumin in Critically Ill Patients With Sepsis

Immunomodulatory Effect of Curcumin in Critically Ill Patients With Sepsis at the Antiguo Hospital Civil de Guadalajara "Fray Antonio Alcalde": A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Sepsis is a life-threatening condition that occurs when the body's response to an infection becomes overwhelming and damages its own organs. It is one of the leading causes of death in critically ill (very sick) patients worldwide. Despite advances in antibiotics, intensive care, and life-support technologies, sepsis remains difficult to treat because much of the harm comes not only from the infection itself, but from an exaggerated and uncontrolled inflammatory response in the body. When a person develops sepsis, the immune system releases large amounts of inflammatory substances meant to fight infection. However, in many cases this response becomes excessive, leading to organ failure, prolonged stays in the intensive care unit (ICU), and increased risk of death. Current treatments focus mainly on controlling the infection and supporting failing organs, but there are limited therapies that directly help regulate this harmful immune overreaction. Curcumin is a natural compound found in turmeric, a spice commonly used in food. In laboratory studies and some clinical research, curcumin has shown anti-inflammatory and antioxidant properties. It appears to influence several pathways in the immune system that are involved in the inflammatory process. However, its potential benefits in patients with severe infections such as sepsis have not been fully studied in a rigorous clinical setting. The purpose of this clinical trial is to evaluate whether curcumin, when added to standard medical treatment, can help modulate (regulate) the immune response in critically ill patients with sepsis. This study will be conducted as a randomized, double-blind, placebo-controlled clinical trial at the Antiguo Hospital Civil de Guadalajara "Fray Antonio Alcalde" in Guadalajara, Mexico. "Randomized" means that participants will be assigned by chance to receive either curcumin or a placebo (a look-alike substance that contains no drug). "Double-blind" means that neither the patients nor the healthcare team will know who is receiving curcumin and who is receiving the placebo during the study. This design helps ensure that the results are objective and scientifically reliable. Participants in the study will continue to receive all standard treatments for sepsis, including antibiotics and intensive care support. The study will measure inflammatory markers in the blood, organ function, and important clinical outcomes such as the need for organ support and length of stay in the ICU. Safety will also be carefully monitored.

Hypothesis:

The investigators hypothesize that in critically ill patients with sepsis, the addition of curcumin to standard treatment will help regulate the excessive inflammatory response, leading to improved biological markers of inflammation and potentially better clinical outcomes, compared to standard treatment alone. If curcumin proves to be beneficial and safe in this population, it could represent an accessible and relatively low-cost complementary therapy to improve the management of sepsis. However, this study is necessary to determine scientifically whether these potential benefits are real and clinically meaningful. The ultimate goal of this research is to contribute new evidence that may improve the care and survival of patients suffering from one of the most severe and challenging conditions treated in intensive care medicine.

Study Overview

• Status: Not yet recruiting
• Conditions: Sepsis
• Intervention / Treatment: Dietary supplement: Curcumin; Drug: Placebo

Detailed Description

Sepsis is a complex, dysregulated host response to infection characterized by systemic inflammation, immune dysfunction, endothelial injury, oxidative stress, microcirculatory alterations, and subsequent organ dysfunction. Despite adherence to guideline-directed management, including early antimicrobial therapy, hemodynamic optimization, and organ support, sepsis continues to be associated with high morbidity and mortality. Increasing evidence suggests that both hyperinflammatory and subsequent immunosuppressive phases contribute to adverse outcomes, highlighting the need for adjunctive immunomodulatory therapies. Curcumin is a bioactive polyphenol derived from Curcuma longa, and has demonstrated anti-inflammatory, antioxidant, and immunomodulatory properties in preclinical models. Curcumin has been shown to modulate multiple intracellular signaling pathways implicated in sepsis pathophysiology, including inhibition of NF-κB activation, downregulation of pro-inflammatory cytokines (e.g., TNF-α, IL-1β, IL-6), attenuation of oxidative stress via Nrf2 activation, and modulation of Toll-like receptor signaling. Additionally, curcumin may influence endothelial function, mitochondrial homeostasis, and apoptosis pathways. However, clinical data in critically ill septic patients remain limited, and robust randomized controlled trials are lacking. This study is designed as a prospective, randomized, double-blind, placebo-controlled clinical trial conducted in critically ill adult patients diagnosed with sepsis and admitted at the Antiguo Hospital Civil de Guadalajara "Fray Antonio Alcalde" in Guadalajara, Mexico. The primary objective is to evaluate whether adjunctive administration of a bioavailable formulation of curcumin, in addition to standard sepsis management, favorably modulates systemic inflammation and organ dysfunction. Participants will be randomly assigned in a 1:1 ratio to receive either curcumin or a matched placebo. Randomization will be performed using a computer-generated sequence with allocation concealment through sequentially numbered, opaque, sealed containers prepared by personnel not involved in patient care or outcome assessment. Blinding will be maintained for participants, treating clinicians, investigators, laboratory personnel, and data analysts. The investigational product and placebo will be identical in appearance, packaging, and administration schedule. All participants will receive standard-of-care management for sepsis according to institutional protocols aligned with international guidelines, including antimicrobial therapy, fluid resuscitation, vasopressor support, ventilatory support, renal replacement therapy, and other organ-support measures as clinically indicated. The intervention consists of adjunctive administration of a standardized, enhanced-bioavailability formulation of curcumin delivered enterally. The dosing regimen, duration of administration, and formulation characteristics are predefined in the protocol and selected based on prior safety data and pharmacokinetic considerations. Enteral administration will occur via oral route or feeding tube in patients receiving enteral nutrition. Treatment will begin within a defined time window after fulfillment of sepsis diagnostic criteria and admission. Adherence to the intervention will be documented daily. Curcumin is known to have limited bioavailability due to poor absorption, rapid metabolism, and systemic elimination. Therefore, the selected formulation incorporates strategies to enhance systemic exposure. The dosing schedule is designed to maintain sustained plasma concentrations within ranges associated with biological activity in prior human studies, while remaining within established safety parameters. Clinical and laboratory data will be collected at baseline and at prespecified time points during their stay. Data will include demographic information, comorbidities, infection source, hemodynamic parameters, organ support requirements, and relevant biochemical markers. Inflammatory and immunologic biomarkers will be measured using validated laboratory techniques. Blood samples will be processed according to standardized protocols to ensure reproducibility and minimize pre-analytical variability. Adverse events will be recorded and categorized according to severity and relatedness to the investigational product. Particular attention will be given to gastrointestinal intolerance, hepatotoxicity, bleeding risk, and allergic reactions. Routine laboratory monitoring will include liver function tests and coagulation parameters to ensure safety. Criteria for discontinuation of the intervention include predefined safety thresholds or clinical judgment by the treating team. Sample size calculation is based on detecting a clinically meaningful difference in predefined biological or clinical parameters between groups, with an appropriate power and two-sided alpha level. The calculation incorporates estimated variance derived from prior studies in similar populations. Statistical analysis will follow the intention-to-treat principle. Continuous variables will be assessed for normality and analyzed using parametric or non-parametric tests as appropriate. Categorical variables will be compared using chi-square or Fisher's exact test. Multivariable analyses will be performed to adjust for potential confounders such as baseline severity of illness, comorbid conditions, and infection source. The study protocol has been submitted to and approved by the institutional Research Ethics Committee. Written informed consent will be obtained from patients or legally authorized representatives prior to enrollment, in accordance with national (Mexican) regulations and the Declaration of Helsinki. Given the critical illness context, provisions are included for surrogate consent when patients lack decision-making capacity. Participants retain the right to withdraw at any time without affecting their standard medical care. Curcumin has an established safety profile in prior human studies at comparable doses, and the risk associated with participation is considered minimal beyond standard treatment. The potential benefit includes improved regulation of systemic inflammation and organ function. This study addresses an important gap in sepsis research by evaluating a multi-target immunomodulatory compound within a rigorous randomized controlled framework. Unlike single-pathway biologic agents that have historically failed in sepsis trials, curcumin exerts pleiotropic effects across inflammatory, oxidative, and endothelial pathways, which may be advantageous in a syndrome characterized by complex immune dysregulation. If adjunctive curcumin therapy demonstrates biological and clinical benefit without increased adverse events, it may represent a cost-effective and accessible strategy for resource-limited settings. Furthermore, this study may provide mechanistic insights into host-response modulation in sepsis and inform future translational research.

• Study Type: Interventional
• Enrollment (Estimated): 56
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kevin S Herrmann-Villatoro, Doctor of Medicine (MD); Phone Number: +52 322 120 9720; Email: kherrmannv99@gmail.com

Study Locations

• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
      • Antiguo Hospital Civil de Guadalajara "Fray Antonio Alcalde"
      • Contact: Kevin S Herrmann-Villatoro, Doctor of Medicine (MD); Phone Number: +52 322 120 9720; Email: kherrmannv99@gmail.com
      • Principal Investigator: Kevin S Herrmann-Villatoro, Doctor of Medicine (MD)
      • Sub-Investigator: Bryan Escamilla-Velázquez, Doctor of Medicine (MD)
      • Sub-Investigator: Iván A Huerta-Mora, Doctor of Medicine (MD)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients older than 18 years of either sex.
• Critically ill patients with a diagnosis of sepsis admitted to the Antiguo Hospital Civil de Guadalajara "Fray Antonio Alcalde."
• Patients receiving enteral nutrition.
• Written informed consent signed by the patient or their legally authorized representative.

Exclusion Criteria:

• Patients with a history of allergy or hypersensitivity to curcumin.
• Patients with autoimmune diseases or severe immunosuppression.
• Patients in a terminal condition with a life expectancy of less than 48 hours.
• Patients with intolerance to enteral feeding, intestinal ischemia, intestinal obstruction, pancreatitis or short bowel syndrome.
• Patients with acute liver failure or decompensated liver cirrhosis.
• Patients with clinically significant active bleeding (e.g., gastrointestinal bleeding, intracranial hemorrhage, etc.).
• Patients requiring therapeutic anticoagulation (warfarin, direct oral anticoagulants [DOACs], or full-dose heparin).
• Patients receiving exclusively parenteral nutrition.
• Pregnant or breastfeeding women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Curcumin + Standard of Care; Participants in this arm will receive standard-of-care treatment for sepsis plus adjunctive curcumin administered enterally. Each patient will receive 2 capsules of curcumin (enhanced-bioavailability curcumin formulation containing 20% curcumin), 500 mg per capsule (100 mg of curcumin per capsule), three times daily for 10 days. This corresponds to a total of 6 capsules per day, providing 600 mg of curcumin daily. Treatment will begin within the predefined enrollment window after diagnosis. All other treatment, including antimicrobials and organ support, will remain at the discretion of the treating team.	Dietary supplement: Curcumin; The investigational product consists of an oral, enhanced-bioavailability formulation of curcumin (Longvida®). Each capsule contains 500 mg of formulation standardized to 20% curcumin, providing 100 mg of active curcumin per capsule. Participants assigned to the experimental arm will receive 2 capsules three times daily (every 8 hours) for 10 consecutive days, for a total of 6 capsules per day and 600 mg of curcumin daily.; Other Names: Diferuloylmethane; Curcuminoid; 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione; Curcumin I; Natural Yellow 3 (E100); Turmeric polyphenol
Placebo Comparator: Placebo + Standard of Care; Participants in this arm will receive standard-of-care treatment for sepsis plus a matched placebo administered enterally. Patients will take 2 starch-based capsules three times daily for 10 days (total of 6 capsules per day), following the same schedule as the experimental arm. The placebo capsules are identical in appearance and packaging to the active product to maintain blinding. All other tratment, including antimicrobials and organ support, will remain at the discretion of the treating team.	Drug: Placebo; Participants randomized to this arm will receive standard-of-care treatment for sepsis plus a matched placebo administered enterally. The placebo consists of starch-based capsules identical in appearance to the active product. Patients will take 2 placebo capsules three times daily for 10 days (total 6 capsules/day), following the same schedule as the experimental arm, while all other treatment remains at the discretion of the treating team.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Interleukin-6 (IL-6) from baseline to Day 10 of treatment.	Serum concentrations of the pro-inflammatory cytokine interleukin-6 (IL-6, pg/mL) will be measured in peripheral venous blood samples collected at baseline (prior to initiation of the intervention) and on Day 10 of treatment. Samples will be processed under standardized laboratory conditions and analyzed using validated quantitative immunoassay techniques (enzyme-linked immunosorbent assay [ELISA]). Results will be reported in pg/mL. The primary endpoint will be defined as the change in cytokine levels from baseline to Day 10, comparing the curcumin and placebo groups. A greater reduction in circulating cytokine concentrations will be interpreted as evidence of a modulatory effect on the systemic inflammatory response associated with sepsis.	Baseline to Day 10
Change in Interleukin-1 beta (IL-1β) from baseline to Day 10 of treatment.	Serum concentrations of the pro-inflammatory cytokine interleukin-1 beta (IL-1β, pg/mL), will be measured in peripheral venous blood samples collected at baseline (prior to initiation of the intervention) and on Day 10 of treatment. Samples will be processed under standardized laboratory conditions and analyzed using validated quantitative immunoassay techniques (enzyme-linked immunosorbent assay [ELISA]). Results will be reported in pg/mL. The primary endpoint will be defined as the change in cytokine levels from baseline to Day 10, comparing the curcumin and placebo groups. A greater reduction in circulating cytokine concentrations will be interpreted as evidence of a modulatory effect on the systemic inflammatory response associated with sepsis.	Baseline to Day 10
Change in tumor necrosis factor-alpha (TNF-α) from baseline to Day 10 of treatment.	Serum concentrations of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α, pg/mL) will be measured in peripheral venous blood samples collected at baseline (prior to initiation of the intervention) and on Day 10 of treatment. Samples will be processed under standardized laboratory conditions and analyzed using validated quantitative immunoassay techniques (enzyme-linked immunosorbent assay [ELISA]). Results will be reported in pg/mL. The primary endpoint will be defined as the change in cytokine levels from baseline to Day 10, comparing the curcumin and placebo groups. A greater reduction in circulating cytokine concentrations will be interpreted as evidence of a modulatory effect on the systemic inflammatory response associated with sepsis.	Baseline to Day 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in high-sensitivity C-reactive protein (hs-CRP) from baseline to Day 10 of treatment.	Serum levels of high-sensitivity C-reactive protein (hs-CRP, mg/L) will be measured at baseline (prior to initiation of the intervention) and on Day 10 of treatment. hs-CRP will be quantified using standardized automated immunoassays. Results will be reported in mg/L. The secondary endpoint will be defined as the change in hs-CRP from baseline to Day 10, comparing the curcumin and placebo groups. A greater reduction in hs-CRP will be interpreted as evidence of attenuation of systemic inflammation.	Baseline to Day 10
Change in procalcitonin (PCT) from baseline to Day 10 of treatment.	Serum levels of procalcitonin (PCT, ng/mL) will be measured at baseline (prior to initiation of the intervention) and on Day 10 of treatment. PCT will be quantified using standardized automated immunoassays. Results will be reported in ng/mL. The secondary endpoint will be defined as the change in PCT from baseline to Day 10, comparing the curcumin and placebo groups. A greater reduction in PCT will be interpreted as evidence of attenuation of systemic inflammation.	Baseline to Day 10
Change in erythrocyte sedimentation rate (ESR) from baseline to Day 10 of treatment.	Serum levels of erythrocyte sedimentation rate (ESR, ng/mL), will be measured at baseline (prior to initiation of the intervention) and on Day 10 of treatment. ESR will be determined using conventional laboratory methodology (Westergren method). Results will be reported in ng/mL. The secondary endpoint will be defined as the change in ESR from baseline to Day 10, comparing the curcumin and placebo groups. A greater reduction in ESR will be interpreted as evidence of attenuation of systemic inflammation.	Baseline to Day 10
Days of Hospital Length of Stay and Days of ICU Length of Stay	Clinical evolution will be evaluated by measuring total hospital length of stay, defined as the number of days from hospital admission to discharge, and ICU length of stay, defined as the number of days from ICU admission to ICU discharge, both reported in days. These outcomes will be compared between the curcumin and placebo groups to determine differences in clinical recovery.	From date of enrollment until the date of hospital discharge; assesed up to 52 weeks
Days of Mechanical Ventilation	Among patients who require mechanical ventilation, the duration of ventilatory support will be measured as the total number of days receiving invasive mechanical ventilation. This outcome will be compared between the curcumin and placebo groups to determine differences in clinical recovery.	From date of intubation until the date of extubation; assesed up to 52 weeks
Number of Deaths (Mortality)	All-cause mortality will be assessed as the proportion of patients who die during hospitalization, expressed as a percentage. This outcome will be compared between the curcumin and placebo groups to determine differences in clinical recovery and overall prognosis.	From date of enrollment until death; assesed up to 52 weeks
Change in "Sequential Organ Failure Assessment" (SOFA) score from baseline to Day 10 of treatment.	Clinical severity will be evaluated using the Sequential Organ Failure Assessment (SOFA) score. It will be calculated according to its validated criteria and reported as total score (0-24 points), higher scores mean a worse outcome. Comparisons between the curcumin and placebo groups will evaluate differences in SOFA score at baseline and Day 10.	Baseline and Day 10
Change in "Sequential Organ Failure Assessment 2" (SOFA-2) score from baseline to Day 10 of treatment.	Clinical severity will be evaluated using the Sequential Organ Failure Assessment 2 (SOFA-2) score. It will be calculated according to its validated criteria and reported as total score (0-24 points), higher scores mean a worse outcome. Comparisons between the curcumin and placebo groups will evaluate differences in SOFA-2 score at baseline and Day 10.	Baseline and Day 10
Change in "Acute Physiology and Chronic Health Evaluation IV" (APACHE IV) score from baseline to Day 10 of treatment	Clinical severity will be evaluated using the Acute Physiology and Chronic Health Evaluation IV (APACHE IV) score. It will be calculated according to its validated criteria and reported as total score (0-286 points), higher scores mean a worse outcome. Comparisons between the curcumin and placebo groups will evaluate differences in APACHE IV score at baseline and Day 10.	Baseline and Day 10
Change in PaO2/FiO2 ratio from baseline to Day 10 of treatment.	Oxygenation status will be assessed using the PaO2/FiO2 ratio, calculated from arterial blood gas analysis and corresponding fraction of inspired oxygen. Results will be reported as unitless ratio, lower ratios mean a worse outcome. Comparisons between the curcumin and placebo groups will evaluate differences in PaO2/FiO2 ratio at baseline and Day 10.	Baseline and Day 10
Change in neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) from baseline to Day 10 of treatment.	Inflammatory status will be evaluated using the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). These will be derived from complete blood count parameters. The results will be expressed as unitless ratios, higher ratios mean a worse outcome. Comparisons between the curcumin and placebo groups will evaluate differences in inflammatory indices at baseline and Day 10.	Baseline and Day 10
Number of participants with adverse events	Safety and tolerability will be assessed by monitoring the incidence, type, and severity of adverse events occurring from the first dose of study medication through Day 10 and up to hospital discharge. Adverse events will be recorded and classified according to clinical severity (mild, moderate, severe) and relationship to the investigational product (unrelated, possibly related, probably related). Serious adverse events will be defined according to standard regulatory criteria, including events resulting in death, life-threatening conditions, prolonged hospitalization, significant disability, or other medically important events. Results will be reported as the total number of adverse events.	From date of first dose until the date of hospital discharge; assesed up to 52 weeks

Collaborators and Investigators

• Sponsor: Hospital Civil de Guadalajara
• Collaborators: University of Guadalajara
• Investigators: Study Director: Enrique Cervantes-Perez, MD and MSc, Hospital Civil de Guadalajara; Study Director: Mariana Chávez-Tostado, BS Nutrition, MSc and PhD, University of Guadalajara

Publications and helpful links

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Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): May 31, 2027

Study Registration Dates

• First Submitted: February 17, 2026
• First Submitted That Met QC Criteria: February 20, 2026
• First Posted (Actual): February 27, 2026

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 20, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Sepsis; Critical Illness; Immunomodulation; Curcumin
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathological Conditions, Signs and Symptoms; Critical Illness; Sepsis; Organic Chemicals; Hydrocarbons, Acyclic; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Heptanes; Alkanes; Catechols; Phenols; Benzene Derivatives; Curcumin; Diarylheptanoids; 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione
• Other Study ID Numbers: CEI 026/26

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data underlying the results reported in publications arising from this study will be shared. This includes demographic variables, baseline clinical characteristics, laboratory measurements (including cytokine levels and inflammatory markers), severity scores, clinical outcomes, and safety data necessary to reproduce the primary and secondary analyses. All shared data will be fully anonymized to protect participant confidentiality and will exclude any direct identifiers.
• IPD Sharing Time Frame: Beginning 1 year after publication with no end date

IPD Sharing Access Criteria

De-identified individual participant data and supporting documents (e.g., study protocol, statistical analysis plan, and informed consent form template) will be made available to qualified researchers upon reasonable request. Access will be granted for scientifically sound research purposes, including secondary analyses, meta-analyses, or validation studies, consistent with the original informed consent and applicable ethical regulations.

Requests must include a research proposal outlining objectives, methodology, and planned analyses. Proposals will be reviewed by the principal investigator and the study research committee to assess scientific merit, ethical appropriateness, and compliance with data protection standards.

The specific data-sharing mechanism has not yet been finalized and will be determined prior to data release in accordance with institutional policies and data protection regulations.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No