Curcumin in Critically Ill Patients With Sepsis

NCT07436130 | Not Yet Recruiting

• 1 other identifier: CEI 026/26
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Sepsis

Keywords

Sepsis; Curcumin; Critical Illness; Immunomodulation

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (12)

• Change in high-sensitivity C-reactive protein (hs-CRP) from baseline to Day 10 of treatment.

  Baseline to Day 10

• Change in procalcitonin (PCT) from baseline to Day 10 of treatment.

  Baseline to Day 10

• Change in erythrocyte sedimentation rate (ESR) from baseline to Day 10 of treatment.

  Baseline to Day 10

• Days of Hospital Length of Stay and Days of ICU Length of Stay

  From date of enrollment until the date of hospital discharge; assesed up to 52 weeks

• Days of Mechanical Ventilation

  From date of intubation until the date of extubation; assesed up to 52 weeks

Study Arms (2)

Curcumin + Standard of Care

EXPERIMENTAL

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

Placebo + Standard of Care

PLACEBO COMPARATOR

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

Interventions

Curcumin DIETARY_SUPPLEMENT

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.

Also known as: Curcuminoid, Diferuloylmethane, 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, Curcumin I, Natural Yellow 3 (E100), Turmeric polyphenol

Curcumin + Standard of Care

Placebo DRUG

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.

Placebo + Standard of Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospital Civil de Guadalajara: lead
• University of Guadalajara: collaborator

Study Sites (1)

Antiguo Hospital Civil de Guadalajara "Fray Antonio Alcalde"

Guadalajara, Jalisco, 44280, Mexico

Location

Related Publications (79)

• Panknin TM, Howe CL, Hauer M, Bucchireddigari B, Rossi AM, Funk JL. Curcumin Supplementation and Human Disease: A Scoping Review of Clinical Trials. Int J Mol Sci. 2023 Feb 24;24(5):4476. doi: 10.3390/ijms24054476.

  PMID: 36901908 BACKGROUND

• Gupte PA, Giramkar SA, Harke SM, Kulkarni SK, Deshmukh AP, Hingorani LL, Mahajan MP, Bhalerao SS. Evaluation of the efficacy and safety of Capsule Longvida(R) Optimized Curcumin (solid lipid curcumin particles) in knee osteoarthritis: a pilot clinical study. J Inflamm Res. 2019 Jun 5;12:145-152. doi: 10.2147/JIR.S205390. eCollection 2019.

  PMID: 31239749 BACKGROUND

• Feng J, Li Z, Tian L, Mu P, Hu Y, Xiong F, Ma X. Efficacy and safety of curcuminoids alone in alleviating pain and dysfunction for knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials. BMC Complement Med Ther. 2022 Oct 19;22(1):276. doi: 10.1186/s12906-022-03740-9.

  PMID: 36261810 BACKGROUND

• Zhong W, Qian K, Xiong J, Ma K, Wang A, Zou Y. Curcumin alleviates lipopolysaccharide induced sepsis and liver failure by suppression of oxidative stress-related inflammation via PI3K/AKT and NF-kappaB related signaling. Biomed Pharmacother. 2016 Oct;83:302-313. doi: 10.1016/j.biopha.2016.06.036. Epub 2016 Jul 7.

  PMID: 27393927 BACKGROUND

• Wang J, Wang H, Zhu R, Liu Q, Fei J, Wang S. Anti-inflammatory activity of curcumin-loaded solid lipid nanoparticles in IL-1beta transgenic mice subjected to the lipopolysaccharide-induced sepsis. Biomaterials. 2015;53:475-83. doi: 10.1016/j.biomaterials.2015.02.116. Epub 2015 Mar 20.

  PMID: 25890744 BACKGROUND

• Zhu H, Wang X, Wang X, Liu B, Yuan Y, Zuo X. Curcumin attenuates inflammation and cell apoptosis through regulating NF-kappaB and JAK2/STAT3 signaling pathway against acute kidney injury. Cell Cycle. 2020 Aug;19(15):1941-1951. doi: 10.1080/15384101.2020.1784599. Epub 2020 Jul 2.

  PMID: 32615888 BACKGROUND

• Yilmaz Savcun G, Ozkan E, Dulundu E, Topaloglu U, Sehirli AO, Tok OE, Ercan F, Sener G. Antioxidant and anti-inflammatory effects of curcumin against hepatorenal oxidative injury in an experimental sepsis model in rats. Ulus Travma Acil Cerrahi Derg. 2013 Nov;19(6):507-15. doi: 10.5505/tjtes.2013.76390.

  PMID: 24347209 BACKGROUND

• Sathyabhama M, Priya Dharshini LC, Karthikeyan A, Kalaiselvi S, Min T. The Credible Role of Curcumin in Oxidative Stress-Mediated Mitochondrial Dysfunction in Mammals. Biomolecules. 2022 Oct 1;12(10):1405. doi: 10.3390/biom12101405.

  PMID: 36291614 BACKGROUND

• Chen D, Wang H, Cai X. Curcumin interferes with sepsis-induced cardiomyocyte apoptosis via TLR1 inhibition. Rev Port Cardiol. 2023 Mar;42(3):209-221. doi: 10.1016/j.repc.2023.01.013. Epub 2023 Jan 23. English, Portuguese.

  PMID: 36702348 BACKGROUND

• Yang C, Wu K, Li SH, You Q. Protective effect of curcumin against cardiac dysfunction in sepsis rats. Pharm Biol. 2013 Apr;51(4):482-7. doi: 10.3109/13880209.2012.742116. Epub 2013 Jan 22.

  PMID: 23336318 BACKGROUND

• Yao Y, Luo R, Xiong S, Zhang C, Zhang Y. Protective effects of curcumin against rat intestinal inflammation-related motility disorders. Mol Med Rep. 2021 May;23(5):391. doi: 10.3892/mmr.2021.12030. Epub 2021 Mar 24.

  PMID: 33760185 BACKGROUND

• Silva LS, Catalao CH, Felippotti TT, Oliveira-Pelegrin GR, Petenusci S, de Freitas LA, Rocha MJ. Curcumin suppresses inflammatory cytokines and heat shock protein 70 release and improves metabolic parameters during experimental sepsis. Pharm Biol. 2017 Dec;55(1):269-276. doi: 10.1080/13880209.2016.1260598.

  PMID: 27927067 BACKGROUND

• Wang Y, Wang Y, Cai N, Xu T, He F. Anti-inflammatory effects of curcumin in acute lung injury: In vivo and in vitro experimental model studies. Int Immunopharmacol. 2021 Jul;96:107600. doi: 10.1016/j.intimp.2021.107600. Epub 2021 Mar 30.

  PMID: 33798807 BACKGROUND

• Gong Z, Zhou J, Li H, Gao Y, Xu C, Zhao S, Chen Y, Cai W, Wu J. Curcumin suppresses NLRP3 inflammasome activation and protects against LPS-induced septic shock. Mol Nutr Food Res. 2015 Nov;59(11):2132-42. doi: 10.1002/mnfr.201500316. Epub 2015 Sep 2.

  PMID: 26250869 BACKGROUND

• Tham CL, Lam KW, Rajajendram R, Cheah YK, Sulaiman MR, Lajis NH, Kim MK, Israf DA. The effects of a synthetic curcuminoid analogue, 2,6-bis-(4-hydroxyl-3-methoxybenzylidine)cyclohexanone on proinflammatory signaling pathways and CLP-induced lethal sepsis in mice. Eur J Pharmacol. 2011 Feb 10;652(1-3):136-44. doi: 10.1016/j.ejphar.2010.10.092. Epub 2010 Nov 30.

  PMID: 21114991 BACKGROUND

• Tham CL, Hazeera Harith H, Wai Lam K, Joong Chong Y, Singh Cheema M, Roslan Sulaiman M, Hj Lajis N, Ahmad Israf D. The synthetic curcuminoid BHMC restores endotoxin-stimulated HUVEC dysfunction:Specific disruption on enzymatic activity of p38 MAPK. Eur J Pharmacol. 2015 Feb 15;749:1-11. doi: 10.1016/j.ejphar.2014.12.015. Epub 2015 Jan 3.

  PMID: 25560198 BACKGROUND

• Monfoulet LE, Mercier S, Bayle D, Tamaian R, Barber-Chamoux N, Morand C, Milenkovic D. Curcumin modulates endothelial permeability and monocyte transendothelial migration by affecting endothelial cell dynamics. Free Radic Biol Med. 2017 Nov;112:109-120. doi: 10.1016/j.freeradbiomed.2017.07.019. Epub 2017 Jul 22.

  PMID: 28739530 BACKGROUND

• Tabrizi R, Vakili S, Akbari M, Mirhosseini N, Lankarani KB, Rahimi M, Mobini M, Jafarnejad S, Vahedpoor Z, Asemi Z. The effects of curcumin-containing supplements on biomarkers of inflammation and oxidative stress: A systematic review and meta-analysis of randomized controlled trials. Phytother Res. 2019 Feb;33(2):253-262. doi: 10.1002/ptr.6226. Epub 2018 Nov 7.

  PMID: 30402990 BACKGROUND

• Chen L, Lu Y, Zhao L, Hu L, Qiu Q, Zhang Z, Li M, Hong G, Wu B, Zhao G, Lu Z. Curcumin attenuates sepsis-induced acute organ dysfunction by preventing inflammation and enhancing the suppressive function of Tregs. Int Immunopharmacol. 2018 Aug;61:1-7. doi: 10.1016/j.intimp.2018.04.041. Epub 2018 May 17.

  PMID: 29778842 BACKGROUND

• Chen HW, Kuo HT, Chai CY, Ou JL, Yang RC. Pretreatment of curcumin attenuates coagulopathy and renal injury in LPS-induced endotoxemia. J Endotoxin Res. 2007;13(1):15-23. doi: 10.1177/0968051907078605.

  PMID: 17621542 BACKGROUND

• Jacob A, Wu R, Zhou M, Wang P. Mechanism of the Anti-inflammatory Effect of Curcumin: PPAR-gamma Activation. PPAR Res. 2007;2007:89369. doi: 10.1155/2007/89369.

  PMID: 18274631 BACKGROUND

• Marquardt JU, Gomez-Quiroz L, Arreguin Camacho LO, Pinna F, Lee YH, Kitade M, Dominguez MP, Castven D, Breuhahn K, Conner EA, Galle PR, Andersen JB, Factor VM, Thorgeirsson SS. Curcumin effectively inhibits oncogenic NF-kappaB signaling and restrains stemness features in liver cancer. J Hepatol. 2015 Sep;63(3):661-9. doi: 10.1016/j.jhep.2015.04.018. Epub 2015 May 1.

  PMID: 25937435 BACKGROUND

• Huang S, Zhao L, Kim K, Lee DS, Hwang DH. Inhibition of Nod2 signaling and target gene expression by curcumin. Mol Pharmacol. 2008 Jul;74(1):274-81. doi: 10.1124/mol.108.046169. Epub 2008 Apr 15.

  PMID: 18413660 BACKGROUND

• Park KR, Lee JH, Choi C, Liu KH, Seog DH, Kim YH, Kim DE, Yun CH, Yea SS. Suppression of interleukin-2 gene expression by isoeugenol is mediated through down-regulation of NF-AT and NF-kappaB. Int Immunopharmacol. 2007 Sep;7(9):1251-8. doi: 10.1016/j.intimp.2007.05.015. Epub 2007 Jun 15.

  PMID: 17630204 BACKGROUND

• Okunieff P, Xu J, Hu D, Liu W, Zhang L, Morrow G, Pentland A, Ryan JL, Ding I. Curcumin protects against radiation-induced acute and chronic cutaneous toxicity in mice and decreases mRNA expression of inflammatory and fibrogenic cytokines. Int J Radiat Oncol Biol Phys. 2006 Jul 1;65(3):890-8. doi: 10.1016/j.ijrobp.2006.03.025.

  PMID: 16751071 BACKGROUND

• Gupta SC, Prasad S, Kim JH, Patchva S, Webb LJ, Priyadarsini IK, Aggarwal BB. Multitargeting by curcumin as revealed by molecular interaction studies. Nat Prod Rep. 2011 Nov;28(12):1937-55. doi: 10.1039/c1np00051a. Epub 2011 Oct 6.

  PMID: 21979811 BACKGROUND

• Xu Y, Liu L. Curcumin alleviates macrophage activation and lung inflammation induced by influenza virus infection through inhibiting the NF-kappaB signaling pathway. Influenza Other Respir Viruses. 2017 Sep;11(5):457-463. doi: 10.1111/irv.12459. Epub 2017 Jul 11.

  PMID: 28646616 BACKGROUND

• Camacho-Barquero L, Villegas I, Sanchez-Calvo JM, Talero E, Sanchez-Fidalgo S, Motilva V, Alarcon de la Lastra C. Curcumin, a Curcuma longa constituent, acts on MAPK p38 pathway modulating COX-2 and iNOS expression in chronic experimental colitis. Int Immunopharmacol. 2007 Mar;7(3):333-42. doi: 10.1016/j.intimp.2006.11.006. Epub 2006 Dec 18.

  PMID: 17276891 BACKGROUND

• Arshad L, Haque MA, Abbas Bukhari SN, Jantan I. An overview of structure-activity relationship studies of curcumin analogs as antioxidant and anti-inflammatory agents. Future Med Chem. 2017 Apr;9(6):605-626. doi: 10.4155/fmc-2016-0223. Epub 2017 Apr 10.

  PMID: 28394628 BACKGROUND

• Jarczak D, Kluge S, Nierhaus A. Sepsis-Pathophysiology and Therapeutic Concepts. Front Med (Lausanne). 2021 May 14;8:628302. doi: 10.3389/fmed.2021.628302. eCollection 2021.

  PMID: 34055825 BACKGROUND

• Nelson KM, Dahlin JL, Bisson J, Graham J, Pauli GF, Walters MA. The Essential Medicinal Chemistry of Curcumin. J Med Chem. 2017 Mar 9;60(5):1620-1637. doi: 10.1021/acs.jmedchem.6b00975. Epub 2017 Jan 11.

  PMID: 28074653 BACKGROUND

• Lao CD, Ruffin MT 4th, Normolle D, Heath DD, Murray SI, Bailey JM, Boggs ME, Crowell J, Rock CL, Brenner DE. Dose escalation of a curcuminoid formulation. BMC Complement Altern Med. 2006 Mar 17;6:10. doi: 10.1186/1472-6882-6-10.

  PMID: 16545122 BACKGROUND

• Pancholi V, Smina TP, Kunnumakkara AB, Maliakel B, Krishnakumar IM. Safety assessment of a highly bioavailable curcumin-galactomannoside complex (CurQfen) in healthy volunteers, with a special reference to the recent hepatotoxic reports of curcumin supplements: A 90-days prospective study. Toxicol Rep. 2021 Jun 16;8:1255-1264. doi: 10.1016/j.toxrep.2021.06.008. eCollection 2021.

  PMID: 34195017 BACKGROUND

• Prasad S, Gupta SC, Tyagi AK, Aggarwal BB. Curcumin, a component of golden spice: from bedside to bench and back. Biotechnol Adv. 2014 Nov 1;32(6):1053-64. doi: 10.1016/j.biotechadv.2014.04.004. Epub 2014 Apr 30.

  PMID: 24793420 BACKGROUND

• Aggarwal BB, Sung B. Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets. Trends Pharmacol Sci. 2009 Feb;30(2):85-94. doi: 10.1016/j.tips.2008.11.002. Epub 2008 Dec 26.

  PMID: 19110321 BACKGROUND

• Aggarwal BB. Targeting inflammation-induced obesity and metabolic diseases by curcumin and other nutraceuticals. Annu Rev Nutr. 2010 Aug 21;30:173-99. doi: 10.1146/annurev.nutr.012809.104755.

  PMID: 20420526 BACKGROUND

• Hatcher H, Planalp R, Cho J, Torti FM, Torti SV. Curcumin: from ancient medicine to current clinical trials. Cell Mol Life Sci. 2008 Jun;65(11):1631-52. doi: 10.1007/s00018-008-7452-4.

  PMID: 18324353 BACKGROUND

• Newman DJ, Cragg GM. Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod. 2012 Mar 23;75(3):311-35. doi: 10.1021/np200906s. Epub 2012 Feb 8.

  PMID: 22316239 BACKGROUND

• Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, Machado FR, Mcintyre L, Ostermann M, Prescott HC, Schorr C, Simpson S, Wiersinga WJ, Alshamsi F, Angus DC, Arabi Y, Azevedo L, Beale R, Beilman G, Belley-Cote E, Burry L, Cecconi M, Centofanti J, Coz Yataco A, De Waele J, Dellinger RP, Doi K, Du B, Estenssoro E, Ferrer R, Gomersall C, Hodgson C, Hylander Moller M, Iwashyna T, Jacob S, Kleinpell R, Klompas M, Koh Y, Kumar A, Kwizera A, Lobo S, Masur H, McGloughlin S, Mehta S, Mehta Y, Mer M, Nunnally M, Oczkowski S, Osborn T, Papathanassoglou E, Perner A, Puskarich M, Roberts J, Schweickert W, Seckel M, Sevransky J, Sprung CL, Welte T, Zimmerman J, Levy M. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med. 2021 Nov 1;49(11):e1063-e1143. doi: 10.1097/CCM.0000000000005337. No abstract available.

  PMID: 34605781 BACKGROUND

• Ferrer R, Martin-Loeches I, Phillips G, Osborn TM, Townsend S, Dellinger RP, Artigas A, Schorr C, Levy MM. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program. Crit Care Med. 2014 Aug;42(8):1749-55. doi: 10.1097/CCM.0000000000000330.

  PMID: 24717459 BACKGROUND

• Rochwerg B, Alhazzani W, Sindi A, Heels-Ansdell D, Thabane L, Fox-Robichaud A, Mbuagbaw L, Szczeklik W, Alshamsi F, Altayyar S, Ip WC, Li G, Wang M, Wludarczyk A, Zhou Q, Guyatt GH, Cook DJ, Jaeschke R, Annane D; Fluids in Sepsis and Septic Shock Group. Fluid resuscitation in sepsis: a systematic review and network meta-analysis. Ann Intern Med. 2014 Sep 2;161(5):347-55. doi: 10.7326/M14-0178.

  PMID: 25047428 BACKGROUND

• Hotchkiss RS, Moldawer LL, Opal SM, Reinhart K, Turnbull IR, Vincent JL. Sepsis and septic shock. Nat Rev Dis Primers. 2016 Jun 30;2:16045. doi: 10.1038/nrdp.2016.45.

  PMID: 28117397 BACKGROUND

• Komori A, Abe T, Kushimoto S, Ogura H, Shiraishi A, Saitoh D, Fujishima S, Mayumi T, Naito T, Hifumi T, Shiino Y, Nakada TA, Tarui T, Otomo Y, Okamoto K, Umemura Y, Kotani J, Sakamoto Y, Sasaki J, Shiraishi SI, Takuma K, Tsuruta R, Hagiwara A, Yamakawa K, Masuno T, Takeyama N, Yamashita N, Ikeda H, Ueyama M, Fujimi S, Gando S; JAAM FORECAST group. Characteristics and outcomes of bacteremia among ICU-admitted patients with severe sepsis. Sci Rep. 2020 Feb 19;10(1):2983. doi: 10.1038/s41598-020-59830-6.

  PMID: 32076046 BACKGROUND

• Jamwal R. Bioavailable curcumin formulations: A review of pharmacokinetic studies in healthy volunteers. J Integr Med. 2018 Nov;16(6):367-374. doi: 10.1016/j.joim.2018.07.001. Epub 2018 Jul 4.

  PMID: 30006023 BACKGROUND

• Hewlings SJ, Kalman DS. Curcumin: A Review of Its Effects on Human Health. Foods. 2017 Oct 22;6(10):92. doi: 10.3390/foods6100092.

  PMID: 29065496 BACKGROUND

• La Via L, Sangiorgio G, Stefani S, Marino A, Nunnari G, Cocuzza S, La Mantia I, Cacopardo B, Stracquadanio S, Spampinato S, Lavalle S, Maniaci A. The Global Burden of Sepsis and Septic Shock. Epidemiologia (Basel). 2024 Jul 25;5(3):456-478. doi: 10.3390/epidemiologia5030032.

  PMID: 39189251 BACKGROUND

• Arina P, Hofmaenner DA, Singer M. Definition and Epidemiology of Sepsis. Semin Respir Crit Care Med. 2024 Aug;45(4):461-468. doi: 10.1055/s-0044-1787990. Epub 2024 Jul 5.

  PMID: 38968960 BACKGROUND

• Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, Machado FR, Mcintyre L, Ostermann M, Prescott HC, Schorr C, Simpson S, Wiersinga WJ, Alshamsi F, Angus DC, Arabi Y, Azevedo L, Beale R, Beilman G, Belley-Cote E, Burry L, Cecconi M, Centofanti J, Coz Yataco A, De Waele J, Dellinger RP, Doi K, Du B, Estenssoro E, Ferrer R, Gomersall C, Hodgson C, Moller MH, Iwashyna T, Jacob S, Kleinpell R, Klompas M, Koh Y, Kumar A, Kwizera A, Lobo S, Masur H, McGloughlin S, Mehta S, Mehta Y, Mer M, Nunnally M, Oczkowski S, Osborn T, Papathanassoglou E, Perner A, Puskarich M, Roberts J, Schweickert W, Seckel M, Sevransky J, Sprung CL, Welte T, Zimmerman J, Levy M. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021 Nov;47(11):1181-1247. doi: 10.1007/s00134-021-06506-y. Epub 2021 Oct 2. No abstract available.

  PMID: 34599691 BACKGROUND

• Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G; SCCM/ESICM/ACCP/ATS/SIS. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003 Apr;31(4):1250-6. doi: 10.1097/01.CCM.0000050454.01978.3B.

  PMID: 12682500 BACKGROUND

• Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992 Jun;101(6):1644-55. doi: 10.1378/chest.101.6.1644.

  PMID: 1303622 BACKGROUND

• Alikiaii B, Khatib N, Badpeyma M, Hasanzadeh E, Abbasi S, Amini S, Kiani Z, Hassanizadeh S, Iraj Z, Sahebkar A, Majeed A, Bagherniya M. Therapeutic effects of curcumin and piperine combination in critically ill patients with sepsis: a randomized double-blind controlled trial. Trials. 2025 Jun 14;26(1):205. doi: 10.1186/s13063-025-08916-5.

  PMID: 40514680 BACKGROUND

• Karimi A, Naeini F, Niazkar HR, Tutunchi H, Musazadeh V, Mahmoodpoor A, Asghariazar V, Mobasseri M, Tarighat-Esfanjani A. Nano-curcumin supplementation in critically ill patients with sepsis: a randomized clinical trial investigating the inflammatory biomarkers, oxidative stress indices, endothelial function, clinical outcomes and nutritional status. Food Funct. 2022 Jun 20;13(12):6596-6612. doi: 10.1039/d1fo03746c.

  PMID: 35621073 BACKGROUND

• Naeini F, Tutunchi H, Razmi H, Mahmoodpoor A, Vajdi M, Sefidmooye Azar P, Najifipour F, Tarighat-Esfanjani A, Karimi A. Does nano-curcumin supplementation improve hematological indices in critically ill patients with sepsis? A randomized controlled clinical trial. J Food Biochem. 2022 May;46(5):e14093. doi: 10.1111/jfbc.14093. Epub 2022 Feb 12.

  PMID: 35150143 BACKGROUND

• Shafiee A, Athar MMT, Shahid A, Ghafoor MS, Ayyan M, Zahid A, Cheema HA. Curcumin for the treatment of COVID-19 patients: A meta-analysis of randomized controlled trials. Phytother Res. 2023 Mar;37(3):1167-1175. doi: 10.1002/ptr.7724. Epub 2023 Jan 14.

  PMID: 36640146 BACKGROUND

• Mokgalaboni K, Mashaba RG, Phoswa WN, Lebelo SL. Curcumin Attenuates Hyperglycemia and Inflammation in Type 2 Diabetes Mellitus: Quantitative Analysis of Randomized Controlled Trial. Nutrients. 2024 Nov 30;16(23):4177. doi: 10.3390/nu16234177.

  PMID: 39683570 BACKGROUND

• Gorabi AM, Razi B, Aslani S, Abbasifard M, Imani D, Sathyapalan T, Sahebkar A. Effect of curcumin on proinflammatory cytokines: A meta-analysis of randomized controlled trials. Cytokine. 2021 Jul;143:155541. doi: 10.1016/j.cyto.2021.155541. Epub 2021 Apr 29.

  PMID: 33934954 BACKGROUND

• Gorabi AM, Abbasifard M, Imani D, Aslani S, Razi B, Alizadeh S, Bagheri-Hosseinabadi Z, Sathyapalan T, Sahebkar A. Effect of curcumin on C-reactive protein as a biomarker of systemic inflammation: An updated meta-analysis of randomized controlled trials. Phytother Res. 2022 Jan;36(1):85-97. doi: 10.1002/ptr.7284. Epub 2021 Sep 29.

  PMID: 34586711 BACKGROUND

• Ferguson JJA, Abbott KA, Garg ML. Anti-inflammatory effects of oral supplementation with curcumin: a systematic review and meta-analysis of randomized controlled trials. Nutr Rev. 2021 Aug 9;79(9):1043-1066. doi: 10.1093/nutrit/nuaa114.

  PMID: 34378053 BACKGROUND

• Marton LT, Pescinini-E-Salzedas LM, Camargo MEC, Barbalho SM, Haber JFDS, Sinatora RV, Detregiachi CRP, Girio RJS, Buchaim DV, Cincotto Dos Santos Bueno P. The Effects of Curcumin on Diabetes Mellitus: A Systematic Review. Front Endocrinol (Lausanne). 2021 May 3;12:669448. doi: 10.3389/fendo.2021.669448. eCollection 2021.

  PMID: 34012421 BACKGROUND

• Panahi Y, Hosseini MS, Khalili N, Naimi E, Simental-Mendia LE, Majeed M, Sahebkar A. Effects of curcumin on serum cytokine concentrations in subjects with metabolic syndrome: A post-hoc analysis of a randomized controlled trial. Biomed Pharmacother. 2016 Aug;82:578-82. doi: 10.1016/j.biopha.2016.05.037. Epub 2016 Jun 6.

  PMID: 27470399 BACKGROUND

• Panahi Y, Ghanei M, Bashiri S, Hajihashemi A, Sahebkar A. Short-term Curcuminoid Supplementation for Chronic Pulmonary Complications due to Sulfur Mustard Intoxication: Positive Results of a Randomized Double-blind Placebo-controlled Trial. Drug Res (Stuttg). 2015 Nov;65(11):567-73. doi: 10.1055/s-0034-1389986. Epub 2014 Sep 30.

  PMID: 25268878 BACKGROUND

• Panahi Y, Saadat A, Beiraghdar F, Sahebkar A. Adjuvant therapy with bioavailability-boosted curcuminoids suppresses systemic inflammation and improves quality of life in patients with solid tumors: a randomized double-blind placebo-controlled trial. Phytother Res. 2014 Oct;28(10):1461-7. doi: 10.1002/ptr.5149. Epub 2014 Mar 19.

  PMID: 24648302 BACKGROUND

• Ganjali S, Sahebkar A, Mahdipour E, Jamialahmadi K, Torabi S, Akhlaghi S, Ferns G, Parizadeh SM, Ghayour-Mobarhan M. Investigation of the effects of curcumin on serum cytokines in obese individuals: a randomized controlled trial. ScientificWorldJournal. 2014 Feb 11;2014:898361. doi: 10.1155/2014/898361. eCollection 2014.

  PMID: 24678280 BACKGROUND

• Gao X, Kuo J, Jiang H, Deeb D, Liu Y, Divine G, Chapman RA, Dulchavsky SA, Gautam SC. Immunomodulatory activity of curcumin: suppression of lymphocyte proliferation, development of cell-mediated cytotoxicity, and cytokine production in vitro. Biochem Pharmacol. 2004 Jul 1;68(1):51-61. doi: 10.1016/j.bcp.2004.03.015.

  PMID: 15183117 BACKGROUND

• Catanzaro M, Corsini E, Rosini M, Racchi M, Lanni C. Immunomodulators Inspired by Nature: A Review on Curcumin and Echinacea. Molecules. 2018 Oct 26;23(11):2778. doi: 10.3390/molecules23112778.

  PMID: 30373170 BACKGROUND

• Gupta SC, Patchva S, Aggarwal BB. Therapeutic roles of curcumin: lessons learned from clinical trials. AAPS J. 2013 Jan;15(1):195-218. doi: 10.1208/s12248-012-9432-8. Epub 2012 Nov 10.

  PMID: 23143785 BACKGROUND

• Karimi A, Ghodsi R, Kooshki F, Karimi M, Asghariazar V, Tarighat-Esfanjani A. Therapeutic effects of curcumin on sepsis and mechanisms of action: A systematic review of preclinical studies. Phytother Res. 2019 Nov;33(11):2798-2820. doi: 10.1002/ptr.6467. Epub 2019 Aug 19.

  PMID: 31429161 BACKGROUND

• Lestari ML, Indrayanto G. Curcumin. Profiles Drug Subst Excip Relat Methodol. 2014;39:113-204. doi: 10.1016/B978-0-12-800173-8.00003-9.

  PMID: 24794906 BACKGROUND

• Kotha RR, Luthria DL. Curcumin: Biological, Pharmaceutical, Nutraceutical, and Analytical Aspects. Molecules. 2019 Aug 13;24(16):2930. doi: 10.3390/molecules24162930.

  PMID: 31412624 BACKGROUND

• Prest J, Sathananthan M, Jeganathan N. Current Trends in Sepsis-Related Mortality in the United States. Crit Care Med. 2021 Aug 1;49(8):1276-1284. doi: 10.1097/CCM.0000000000005017.

  PMID: 34261926 BACKGROUND

• Lelubre C, Vincent JL. Mechanisms and treatment of organ failure in sepsis. Nat Rev Nephrol. 2018 Jul;14(7):417-427. doi: 10.1038/s41581-018-0005-7.

  PMID: 29691495 BACKGROUND

• Gyawali B, Ramakrishna K, Dhamoon AS. Sepsis: The evolution in definition, pathophysiology, and management. SAGE Open Med. 2019 Mar 21;7:2050312119835043. doi: 10.1177/2050312119835043. eCollection 2019.

  PMID: 30915218 BACKGROUND

• Arora J, Mendelson AA, Fox-Robichaud A. Sepsis: network pathophysiology and implications for early diagnosis. Am J Physiol Regul Integr Comp Physiol. 2023 May 1;324(5):R613-R624. doi: 10.1152/ajpregu.00003.2023. Epub 2023 Mar 6.

  PMID: 36878489 BACKGROUND

• Paoli CJ, Reynolds MA, Sinha M, Gitlin M, Crouser E. Epidemiology and Costs of Sepsis in the United States-An Analysis Based on Timing of Diagnosis and Severity Level. Crit Care Med. 2018 Dec;46(12):1889-1897. doi: 10.1097/CCM.0000000000003342.

  PMID: 30048332 BACKGROUND

• Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, Colombara DV, Ikuta KS, Kissoon N, Finfer S, Fleischmann-Struzek C, Machado FR, Reinhart KK, Rowan K, Seymour CW, Watson RS, West TE, Marinho F, Hay SI, Lozano R, Lopez AD, Angus DC, Murray CJL, Naghavi M. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet. 2020 Jan 18;395(10219):200-211. doi: 10.1016/S0140-6736(19)32989-7.

  PMID: 31954465 BACKGROUND

• Chiu C, Legrand M. Epidemiology of sepsis and septic shock. Curr Opin Anaesthesiol. 2021 Apr 1;34(2):71-76. doi: 10.1097/ACO.0000000000000958.

  PMID: 33492864 BACKGROUND

• Arina P, Singer M. Pathophysiology of sepsis. Curr Opin Anaesthesiol. 2021 Apr 1;34(2):77-84. doi: 10.1097/ACO.0000000000000963.

  PMID: 33652454 BACKGROUND

• Esposito S, De Simone G, Boccia G, De Caro F, Pagliano P. Sepsis and septic shock: New definitions, new diagnostic and therapeutic approaches. J Glob Antimicrob Resist. 2017 Sep;10:204-212. doi: 10.1016/j.jgar.2017.06.013. Epub 2017 Jul 22.

  PMID: 28743646 BACKGROUND

• Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.

  PMID: 26903338 BACKGROUND

MeSH Terms

Conditions

Sepsis; Critical Illness

Interventions

Curcumin; Diarylheptanoids; 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Intervention Hierarchy (Ancestors)

Heptanes; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic

Study Officials

• Enrique Cervantes-Perez, MD and MSc

  Hospital Civil de Guadalajara

  STUDY DIRECTOR

• Mariana Chávez-Tostado, BS Nutrition, MSc and PhD

  University of Guadalajara

  STUDY DIRECTOR

Central Study Contacts

Kevin S Herrmann-Villatoro, Doctor of Medicine (MD)

CONTACT

+52 322 120 9720; kherrmannv99@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Internal Medicine Resident

Model Details: This study is designed as a prospective, randomized, parallel-group interventional clinical trial

Study Record Dates

• First Submitted: February 17, 2026
• First Posted: February 27, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): May 31, 2027
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 1 year after publication with no end date
• 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.

Locations

ME (1)