Septic ShockPhase 2NCT06225258
Xanthohumol as an Adjuvant in the Treatment of Septic Shock
A Phase 2 study testing Xanthohumol in people with Septic Shock and Pneumonia, run by Medical University of Lublin at 1 site in Poland.
Trial summary
Septic shock (SS) is a life-threatening condition resulting from excessive inflammatory response to bacterial, viral or/and fungal infections. It is associated with dysregulation of the immune system, activation of immune cells, and massive release of cytokines, commonly known as the cytokine storm (CS). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock, Pneumonia, ARDS
- What is being tested?
- Xanthohumol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 sitePoland
- Study dates
- 9 Jan 2023to 31 Dec 2025
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- a septic shock in the early, acute phase,
- respiratory insufficiency required mechanical ventilation with PaO2/FiO2 < 150,
- bacterial infection,
- procalcitonin higher than 5 ng/mL and interleukin 6 higher than 100 pg/mL,
- no allergy to hops or their derivatives,
- hemodynamic instability requiring vasopressor infusions
Who cannot join
- lack of agreement
- septic shock treated for more than 1 day,
- history of severe chronic cardiac, pulmonary and/or liver diseases
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Poland1 site, 1 recruiting
- Recruiting
Intensive Care Unit, University Hospital No 4,
Lublin, Lublin Voivodeship, 20-954
Wojciech Dabrowski, Prof MD PhD, +48817244332, wojciech.dabrowski@umlub.pl
Wojciech Dabrowski, Prof, MD PhD, +48817244332, wojciech.dabrowski@umlub.pl
About this study
Official title: Analysis of Anti-inflammatory Effect of Hop Extract Rich in Xanthohumol in Patients Treated for Septic Shock
Septic shock (SS) is a life-threatening condition resulting from excessive inflammatory response to bacterial, viral or/and fungal infections. It is associated with dysregulation of the immune system, activation of immune cells, and massive release of cytokines, commonly known as the cytokine storm (CS). The clinical manifestations of SS depend on the initial site of infection. However, the classic symptoms are associated with severe dysfunction of the respiratory and cardiovascular systems, which are observed from the early phase. Respiratory insufficiency frequently requires different forms of oxygen supplementation, including mechanical ventilation and even extracorporeal oxygenation. The severity of respiratory and other organ dysfunction depends on the inflammatory response to the infection and circulating toxins, which correspond to excessive cytokine release. In the past years, several studies documented that reduction of SS-related inflammatory response and CS improved organ function and alleviated the clinical course of SS. Unfortunately, an effective strong anti-inflammatory without side effects medications has not yet been found. Therefore, the use of natural anti-inflammatory and antioxidant substances seems very promising.
Xanthohumol (Xn) is a natural prenylated chalcone extracted from the female inflorescences of hop cones (Humulus lupus) and possesses strong anti-inflammatory and antioxidant properties. It is widely used as a supplement to diet. Xanthohumol inhibits CS and has been showed to be an effective medication for reducing the severity of lung injury. It has been documented that Xn inhibits proinflammatory pathways in a different manner. A decrease in cytokine production and release can affect endothelial function and correct inflammatory-related vascular hyperpermeability, reducing uncontrolled water shift to extravascular space and then tissue edema. Clinical observation showed that administration of Xn alleviated clinical course, improved respiratory function, and reduced mortality in critically ill COVID-19 patients. Xanthohumol is safe and well tolerated by humans, and no adverse effects have been reported yet. Based on its strong anti-inflammatory and antioxidative properties, it can be speculated that the use of Xn can effectively reduce the inflammatory response and improve the clinical course in SS patients.
- Conditions
- Septic Shock, Pneumonia, ARDS
- Being tested
- Xanthohumol
- Keywords
- septic shock, inflammation, Xanthohumol, adjuvant, endotheliopathy, ARDS, cytokine
- Medical subject headings
- Shock, Septic, Pneumonia, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XanthohumolDietary supplement
Also called ChmielXnActive (Salutis Pharmacy, Poland)
Patients, who received Xanthohumol (Chmiel-Xn-Active, SALUTIS Pharmacy, Poland) as adjunctive therapy to treatment recommended by Surviving Sepsis Campaign. Xanthohumol is administrated by the nosogastric tube three times a day *every 8 hours) at the dose of 2 mg.\/kg body weight for 10 days. The first dose of Xanthohumol is administrated within 4 hours after the admission to the ICU.
| Study group | Role | What they receive |
|---|---|---|
| Group C | No intervention | Patients are treated according to the recommendations of the Surviving Sepsis Campaign. |
| Group Xn | Experimental | Patients, who are admitted to the Intensive Care Unit (ICU) due to septic shock in the early, acute phase. Patients are treated according to the recommendations of the Surviving Sepsis Campaign and receive xanthohumol at a dose of 2 mg per kg body weight administered via nasogastric tube as supportive therapy. Receives: Dietary Supplement: Xanthohumol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Xanthohumol as an adjunctive treatment improves clinical course in ill septic shock patents
Xanthohumol as an adjunctive treatment can significantly reduce mortality and length of hospitalization in critically ill patients. This effect can be reflected by analysis of the mortality rate on days 7 and 28 after the admission to the ICU.
Measured: 7 and 28 days mortality
Xanthohumol as an adjunctive treatmenty affects a severity of inflammation
The use of xanthohumol as adjunctive treatment can reduce the inflammatory response in the acute early phase of septic shock. Plasma concentrations of pro-inflammatory cytokines can reflect this effect. Blood samples are collected from arterial access at nine time points: just after ICU admission (baseline) and in the morning on days 1, 2, 3, 4, 5, and 6 after ICU admission.
Measured: 7 time points: just after ICU admission and on the days 1,2,3,4,5 and 6 after ICU admission.
Xanthohumol as an adjunctive treatment affects sepsis-related glycocalyx injury
The use of xanthohumol as adjunctive treatment can reduce septic-induced glycocalyx injury. The severity of glycocalyx damage can be measured by changes in plasma biomarker concentrations, which are typical of glycocalyx damage. Blood samples are collected from arterial access at nine time points: just after ICU admission (baseline) and in the morning on days 1, 2, 3, 4, 5, and 6 after ICU admission.
Measured: 7 time points: just after ICU admission and on the days 1,2,3,4,5 and 6 after ICU admission.
Secondary outcomes (11)
Xanthohumol as an adjunctive treatment affects plasma interleukin 1beta concentration.
Interleukin 1beta, also known as lymphocyte activating factor, is produced and released by activated macrophages and monocytes and is important biomarker of inflammatory response. Its elevated concentrations relate to severity of inflammation, while its reduction corresponds to effective treatment. Rapid decrease in the circulating interleukin 1beta concentration may confirm the efficacy of Xanthohumol in critically ill patients treated for septic shock.
Blood samples are collected from arterial access at nine time points: just after ICU admission (baseline) and in the morning on days 1, 2, 3, 4, 5, and 6 after ICU admission.
Measured: 7 time points: just after ICU admission and on the days 1,2,3,4,5 and 6 after ICU admission.
Xanthohumol as an adjunctive treatment changes plasma tumor necrosis factor-alpha concentration.
Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine released by different cells including macrophages, endothelial cells, lymphoid cells and others to stimulate the immune system into an inflammatory response. It is released as a response to lipopolysaccharide or other bacterial products following infection. A high concentration of TNF-alpha corresponds to the severity of inflammatory response and endothelial hyper-permeability with glycocalyx damage. Rapid decrease in the circulating TNF-alpha concentration may confirm the efficacy of Xanthohumol in critically ill patients treated for septic shock. Blood samples are collected from arterial access at nine time points: just after ICU admission (baseline) and in the morning on days 1, 2, 3, 4, 5, and 6 after ICU admission.
Measured: 7 time points: just after ICU admission and on the days 1,2,3,4,5 and 6 after ICU admission.
Xanthohumol as an adjunctive treatment affects plasma interleukin 6 concentration.
Interleukin 6 is the most recognized pro-inflammatory cytokine. It is also anty-inflammatory myokine. Interleukine 6 is released by macrophages in response to microbial molecules such as pathogen-associated molecular patterns or damage-associated molecular patterns. Interleukin 6 is an important mediator of fever and of the acute phase of inflammatory response. A rapid decrease in the circulating interleukin 6 concentration may confirm the efficacy of Xanthohumol in critically ill patients treated for septic shock. Blood samples are collected from arterial access at nine time points: just after ICU admission (baseline) and in the morning on days 1, 2, 3, 4, 5, and 6 after ICU admission.
Measured: 7 time points: just after ICU admission and on the days 1,2,3,4,5 and 6 after ICU admission.
Xanthohumol as an adjunctive treatment affects plasma interleukin 8 concentration.
Interleukin 8 is a chemokine produced by different cells including macrophages and epithelial cells. It is a mediator associated with inflammation and plays a crucial role in neutrophil recruitment and neutrophil degranulation. Interleukin 8 is secreted as a response to oxidant stress. It correlates with endothelial injury. Its rapid decrease in the circulating blood may confirm the efficacy of Xanthohumol in critically ill patients treated for septic shock. Blood samples are collected from arterial access at nine time points: just after ICU admission (baseline) and in the morning on days 1, 2, 3, 4, 5, and 6 after ICU admission.
Measured: 7 time points: just after ICU admission and on the days 1,2,3,4,5 and 6 after ICU admission.
Xanthohumol as an adjunctive treatment affects plasma interleukin 17 concentration
Interleukin 17 is a pro-inflammatory cytokine that is produced by a group of T helper cells known as T helper 17 cells in response to their stimulation with interleukin 23. Its elevated concentrations correspond to the severity of inflammation, while its reduction corresponds to effective treatment. A decrease in its concentration in the circulating blood may confirm the efficacy of Xanthohumol in critically ill patients treated for septic shock. Blood samples are collected from arterial access at nine time points: just after ICU admission (baseline) and in the morning on days 1, 2, 3, 4, 5, and 6 after ICU admission.
Measured: 7 time points: just after ICU admission and on the days 1,2,3,4,5 and 6 after ICU admission.
Xanthohumol as an adjunctive treatment affects plasma interleukin 23 concentration.
Interleukin 23 is an inflammatory cytokine secreted by activated dendric cells, macrophages, or monocytes. IL-23 is also produced by B cells through B cell antigen receptor signaling. Polarisation to a Th17 phenotype is triggered by interleukin-6. Rapid decrease in the circulating IL-23 concentration may reflect changes in IL-17 concentration that confirm the efficacy of Xanthohumol in critically ill patients treated for septic shock. Blood samples are collected from arterial access at nine time points: just after ICU admission (baseline) and in the morning on days 1, 2, 3, 4, 5, and 6 after ICU admission.
Measured: 7 time points: just after ICU admission and on the days 1,2,3,4,5 and 6 after ICU admission.
Xanthohumol as an adjunctive treatment affects plasma interleukin 40 concentration
Interleukin 40 is synthetized by C17orf99 and activated B cells after being stimulated with anti-CD40 monoclonal antibodies. It is a key effector in the humoral immune system. IL-40 exerts proinflammatory effects. Decrease in IL-40 may confirm the efficacy of Xanthohumol in critically ill patients treated for septic shock. Blood samples are collected from arterial access at nine time points: just after ICU admission (baseline) and in the morning on days 1, 2, 3, 4, 5, and 6 after ICU admission.
Measured: 7 time points: just after ICU admission and on the days 1,2,3,4,5 and 6 after ICU admission.
Xanthohumol as an adjunctive treatment affects plasma syndecan 1 concentration.
Syndecan-1 is a heparan sulfate proteoglycan expressed in endothelial cells and is a well-known marker of endothelial glycocalyx degradation. Its elevated plasma concentration corresponds to endothelial injury and was noted in septic shock patients. A decrease in the inflammatory response following Xanthohumol administration reduces the severity of glycocalyx damage and endothelial injury. Blood samples are collected from arterial access at nine time points: just after ICU admission (baseline) and in the morning on days 1, 2, 3, 4, 5, and 6 after ICU admission.
Measured: 7 time points: just after ICU admission and on the days 1,2,3,4,5 and 6 after ICU admission.
Xanthohumol as an adjunctive treatment affects plasma vascular endothelial adhesion molecule 1 concentration.
Vascular endothelial adhesion molecule 1 is a protein expressed in endothelial cells in response to pro-inflammatory cytokines including interleukine1 and tumor necrosis factor-alpha or bacterial endotoxin. Its elevated plasma concentration correlates with disorders in vascular permeability and documents endothelial damage following inflammation. A decrease in the severity of inflammation and the amount of circulating pro-inflammatory cytokines can reduce the severity of endothelial injury reflected by a decrease in plasma vascular endothelial adhesion molecule 1 concentration. Blood samples are collected from arterial access at nine time points: just after ICU admission (baseline) and in the morning on days 1, 2, 3, 4, 5, and 6 after ICU admission.
Measured: 7 time points: just after ICU admission and on the days 1,2,3,4,5 and 6 after ICU admission.
Xanthohumol as an adjunctive treatment affects plasma E-selectin concentration.
E-selectin is a glycoprotein expressed on endothelial cells after activation by interleukin 1beta, tumor necrosis factor-alpha, or bacterial lipopolysaccharides. Its expression is crucial to control leukocyte accumulation in inflammatory responses. Elevated plasma E-selectin concentration was documented in sepsis and patients treated for inflammatory diseases without septic syndromes. Plasma E-selectin concentration correlates with the severity of inflammation and endothelial damage. A decrease in the severity of inflammation and the amount of circulating pro-inflammatory cytokines can reduce the severity of endothelial injury reflected by a decrease in plasma vascular endothelial adhesion molecule 1 concentration. Blood samples are collected from arterial access at nine time points: just after ICU admission (baseline) and in the morning on days 1, 2, 3, 4, 5, and 6 after ICU admission.
Measured: 7 time points: just after ICU admission and on the days 1,2,3,4,5 and 6 after ICU admission.
Xanthohumol as an adjunctive treatment affects plasma vascular endothelial growth factor concentration.
Vascular endothelial growth factor (VEGF) is a protein, which is considered as a sensitive marker of endothelial damage and vascular permeability. It is originally known as vascular permeability factor. VEGF-A production can be induced in the endothelial cells by circulating cytokines and severe hypoxia. A decrease in the severity of inflammation and the amount of circulating pro-inflammatory cytokines can reduce the severity of endothelial injury reflected by a decrease in VEGF-A concentration. Blood samples are collected from arterial access at nine time points: just after ICU admission (baseline) and in the morning on days 1, 2, 3, 4, 5, and 6 after ICU admission.
Measured: 7 time points: just after ICU admission and on the days 1,2,3,4,5 and 6 after ICU admission.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2024
- Study start9 Jan 2023
- Primary completion30 Oct 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (22)Papers the sponsor has linked to this study.
- Other trials for Septic ShockStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients are randomised in a double-blind, placebo-controlled manner to two groups using sealed envelopes. In the intervention group, all patients receive Xanthohumol as adjunctive therapy as recommended by the Surviving Sepsis Campaign. In the control group, patients are treated without Xanthohumol as recommended by the Surviving Sepsis Campaign and are treated as recommended by Surviving Sepsis. Bioavailability, clinical and possible side effects are monitored.
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of Lublin
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Wojciech Dabrowski, Prof, Study chair, Medical University of Lublin, PolandWlodzimierz Plotek, Principal investigator, Medical University of Lublin, Poland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06225258
- Sponsor's protocol ID
- SEPXN
- Status last verified
- Jul 2025
- First submitted
- 21 Dec 2023
- Last updated
- 4 Jul 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Bartmanska A, Tronina T, Poplonski J, Huszcza E. Biotransformations of prenylated hop flavonoids for drug discovery and production. Curr Drug Metab. 2013 Dec;14(10):1083-97. doi: 10.2174/1389200214666131211151855.
PubMed 24329115Bosmann M, Ward PA. The inflammatory response in sepsis. Trends Immunol. 2013 Mar;34(3):129-36. doi: 10.1016/j.it.2012.09.004. Epub 2012 Oct 2.
PubMed 23036432Chen X, Li Z, Hong H, Wang N, Chen J, Lu S, Zhang H, Zhang X, Bei C. Xanthohumol suppresses inflammation in chondrocytes and ameliorates osteoarthritis in mice. Biomed Pharmacother. 2021 May;137:111238. doi: 10.1016/j.biopha.2021.111238. Epub 2021 Jan 28.
PubMed 33517187Corrado C, Barreca MM, Raimondo S, Diana P, Pepe G, Basilicata MG, Conigliaro A, Alessandro R. Nobiletin and xanthohumol counteract the TNFalpha-mediated activation of endothelial cells through the inhibition of the NF-kappaB signaling pathway. Cell Biol Int. 2023 Mar;47(3):634-647. doi: 10.1002/cbin.11963. Epub 2022 Nov 15.
PubMed 36378586Costa R, Negrao R, Valente I, Castela A, Duarte D, Guardao L, Magalhaes PJ, Rodrigues JA, Guimaraes JT, Gomes P, Soares R. Xanthohumol modulates inflammation, oxidative stress, and angiogenesis in type 1 diabetic rat skin wound healing. J Nat Prod. 2013 Nov 22;76(11):2047-53. doi: 10.1021/np4002898. Epub 2013 Nov 7.
PubMed 24200239Dabrowski W, Gagos M, Siwicka-Gieroba D, Piechota M, Siwiec J, Bielacz M, Kotfis K, Stepulak A, Grzycka-Kowalczyk L, Jaroszynski A, Malbrain ML. Humulus lupus extract rich in xanthohumol improves the clinical course in critically ill COVID-19 patients. Biomed Pharmacother. 2023 Feb;158:114082. doi: 10.1016/j.biopha.2022.114082. Epub 2022 Dec 9.
PubMed 36508996Dartiguelongue JB. Systemic inflammation and sepsis. Part I: Storm formation. Arch Argent Pediatr. 2020 Dec;118(6):e527-e535. doi: 10.5546/aap.2020.eng.e527. English, Spanish.
PubMed 33231055Chong DLW, Sriskandan S. Pro-inflammatory mechanisms in sepsis. Contrib Microbiol. 2011;17:86-107. doi: 10.1159/000324022. Epub 2011 Jun 9.
PubMed 21659748Gaudette S, Smart L, Woodward AP, Sharp CR, Hughes D, Bailey SR, Dandrieux JRS, Santos L, Boller M. Biomarkers of endothelial activation and inflammation in dogs with organ dysfunction secondary to sepsis. Front Vet Sci. 2023 Jul 13;10:1127099. doi: 10.3389/fvets.2023.1127099. eCollection 2023.
PubMed 37520007Girisa S, Saikia Q, Bordoloi D, Banik K, Monisha J, Daimary UD, Verma E, Ahn KS, Kunnumakkara AB. Xanthohumol from Hop: Hope for cancer prevention and treatment. IUBMB Life. 2021 Aug;73(8):1016-1044. doi: 10.1002/iub.2522. Epub 2021 Jul 6.
PubMed 34170599Jung F, Staltner R, Tahir A, Baumann A, Burger K, Halilbasic E, Hellerbrand C, Bergheim I. Oral intake of xanthohumol attenuates lipoteichoic acid-induced inflammatory response in human PBMCs. Eur J Nutr. 2022 Dec;61(8):4155-4166. doi: 10.1007/s00394-022-02964-2. Epub 2022 Jul 20.
PubMed 35857130Lee IS, Lim J, Gal J, Kang JC, Kim HJ, Kang BY, Choi HJ. Anti-inflammatory activity of xanthohumol involves heme oxygenase-1 induction via NRF2-ARE signaling in microglial BV2 cells. Neurochem Int. 2011 Feb;58(2):153-60. doi: 10.1016/j.neuint.2010.11.008. Epub 2010 Nov 18.
PubMed 21093515Li F, Yao Y, Huang H, Hao H, Ying M. Xanthohumol attenuates cisplatin-induced nephrotoxicity through inhibiting NF-kappaB and activating Nrf2 signaling pathways. Int Immunopharmacol. 2018 Aug;61:277-282. doi: 10.1016/j.intimp.2018.05.017. Epub 2018 Jun 12.
PubMed 29906742Lin Y, Zang R, Ma Y, Wang Z, Li L, Ding S, Zhang R, Wei Z, Yang J, Wang X. Xanthohumol Is a Potent Pan-Inhibitor of Coronaviruses Targeting Main Protease. Int J Mol Sci. 2021 Nov 9;22(22):12134. doi: 10.3390/ijms222212134.
PubMed 34830015Luescher S, Urmann C, Butterweck V. Effect of Hops Derived Prenylated Phenols on TNF-alpha Induced Barrier Dysfunction in Intestinal Epithelial Cells. J Nat Prod. 2017 Apr 28;80(4):925-931. doi: 10.1021/acs.jnatprod.6b00869. Epub 2017 Feb 24.
PubMed 28234482
Study at a glance
From the registry record, last updated by the sponsor on 4 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Analysis of Anti-inflammatory Effect of Hop Extract Rich in Xanthohumol in Patients Treated for Septic Shock
- ClinicalTrials.gov ID
- NCT06225258
- Acronym / sponsor ID
- SEPXN
- Conditions
- Septic Shock, Pneumonia, ARDS
- Keywords
- septic shock, inflammation, Xanthohumol, adjuvant, endotheliopathy, ARDS, cytokine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Medical University of LublinUniversity, hospital or other
- Study start
- 9 Jan 2023 (actual)
- Primary completion
- 30 Oct 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 25 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Septic shock (SS) is a life-threatening condition resulting from excessive inflammatory response to bacterial, viral or/and fungal infections. It is associated with dysregulation of the immune system, activation of immune cells, and massive release of cytokines, commonly known as the cytokine storm (CS). The clinical manifestations of SS depend on the initial site of infection. However, the classic symptoms are associated with severe dysfunction of the respiratory and cardiovascular systems, which are observed from the early phase. Respiratory insufficiency frequently requires different forms of oxygen supplementation, including mechanical ventilation and even extracorporeal oxygenation. The severity of respiratory and other organ dysfunction depends on the inflammatory response to the infection and circulating toxins, which correspond to excessive cytokine release. In the past years, several studies documented that reduction of SS-related inflammatory response and CS improved organ function and alleviated the clinical course of SS. Unfortunately, an effective strong anti-inflammatory without side effects medications has not yet been found. Therefore, the use of natural anti-inflammatory and antioxidant substances seems very promising.
Xanthohumol (Xn) is a natural prenylated chalcone extracted from the female inflorescences of hop cones (Humulus lupus) and possesses strong anti-inflammatory and antioxidant properties. It is widely used as a supplement to diet. Xanthohumol inhibits CS and has been showed to be an effective medication for reducing the severity of lung injury. It has been documented that Xn inhibits proinflammatory pathways in a different manner. A decrease in cytokine production and release can affect endothelial function and correct inflammatory-related vascular hyperpermeability, reducing uncontrolled water shift to extravascular space and then tissue edema. Clinical observation showed that administration of Xn alleviated clinical course, improved respiratory function, and reduced mortality in critically ill COVID-19 patients. Xanthohumol is safe and well tolerated by humans, and no adverse effects have been reported yet. Based on its strong anti-inflammatory and antioxidative properties, it can be speculated that the use of Xn can effectively reduce the inflammatory response and improve the clinical course in SS patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
- Model description
- Patients are randomised in a double-blind, placebo-controlled manner to two groups using sealed envelopes. In the intervention group, all patients receive Xanthohumol as adjunctive therapy as recommended by the Surviving Sepsis Campaign. In the control group, patients are treated without Xanthohumol as recommended by the Surviving Sepsis Campaign and are treated as recommended by Surviving Sepsis. Bioavailability, clinical and possible side effects are monitored.
| Arm | Type | Receives |
|---|---|---|
| Group C | No intervention | –Patients are treated according to the recommendations of the Surviving Sepsis Campaign. |
| Group Xn | Experimental | Dietary Supplement: XanthohumolPatients, who are admitted to the Intensive Care Unit (ICU) due to septic shock in the early, acute phase. Patients are treated according to the recommendations of the Surviving Sepsis Campaign and receive xanthohumol at a dose of 2 mg per kg body weight administered via nasogastric tube as supportive therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- a septic shock in the early, acute phase,
- respiratory insufficiency required mechanical ventilation with PaO2/FiO2 < 150,
- bacterial infection,
- procalcitonin higher than 5 ng/mL and interleukin 6 higher than 100 pg/mL,
- no allergy to hops or their derivatives,
Key exclusion criteria (3 listed)
- lack of agreement
- septic shock treated for more than 1 day,
- history of severe chronic cardiac, pulmonary and/or liver diseases
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 |
|---|---|---|
| XanthohumolAlso: ChmielXnActive (Salutis Pharmacy, Poland)Patients, who received Xanthohumol (Chmiel-Xn-Active, SALUTIS Pharmacy, Poland) as adjunctive therapy to treatment recommended by Surviving Sepsis Campaign. Xanthohumol is administrated by the nosogastric tube three times a day *every 8 hours) at the dose of 2 mg.\/kg body weight for 10 days. The first dose of Xanthohumol is administrated within 4 hours after the admission to the ICU. | Dietary supplement | Group Xn |
Primary outcome
Xanthohumol as an adjunctive treatment improves clinical course in ill septic shock patents
Time frame: 7 and 28 days mortality
Xanthohumol as an adjunctive treatment can significantly reduce mortality and length of hospitalization in critically ill patients. This effect can be reflected by analysis of the mortality rate on days 7 and 28 after the admission to the ICU.
Xanthohumol as an adjunctive treatmenty affects a severity of inflammation
Time frame: 7 time points: just after ICU admission and on the days 1,2,3,4,5 and 6 after ICU admission.
The use of xanthohumol as adjunctive treatment can reduce the inflammatory response in the acute early phase of septic shock. Plasma concentrations of pro-inflammatory cytokines can reflect this effect. Blood samples are collected from arterial access at nine time points: just after ICU admission (baseline) and in the morning on days 1, 2, 3, 4, 5, and 6 after ICU admission.
Xanthohumol as an adjunctive treatment affects sepsis-related glycocalyx injury
Time frame: 7 time points: just after ICU admission and on the days 1,2,3,4,5 and 6 after ICU admission.
The use of xanthohumol as adjunctive treatment can reduce septic-induced glycocalyx injury. The severity of glycocalyx damage can be measured by changes in plasma biomarker concentrations, which are typical of glycocalyx damage. Blood samples are collected from arterial access at nine time points: just after ICU admission (baseline) and in the morning on days 1, 2, 3, 4, 5, and 6 after ICU admission.
11 secondary outcomes
Xanthohumol as an adjunctive treatment affects plasma interleukin 1beta concentration.
Time frame: 7 time points: just after ICU admission and on the days 1,2,3,4,5 and 6 after ICU admission.
Xanthohumol as an adjunctive treatment changes plasma tumor necrosis factor-alpha concentration.
Time frame: 7 time points: just after ICU admission and on the days 1,2,3,4,5 and 6 after ICU admission.
Xanthohumol as an adjunctive treatment affects plasma interleukin 6 concentration.
Time frame: 7 time points: just after ICU admission and on the days 1,2,3,4,5 and 6 after ICU admission.
Xanthohumol as an adjunctive treatment affects plasma interleukin 8 concentration.
Time frame: 7 time points: just after ICU admission and on the days 1,2,3,4,5 and 6 after ICU admission.
Xanthohumol as an adjunctive treatment affects plasma interleukin 17 concentration
Time frame: 7 time points: just after ICU admission and on the days 1,2,3,4,5 and 6 after ICU admission.
Xanthohumol as an adjunctive treatment affects plasma interleukin 23 concentration.
Time frame: 7 time points: just after ICU admission and on the days 1,2,3,4,5 and 6 after ICU admission.
Xanthohumol as an adjunctive treatment affects plasma interleukin 40 concentration
Time frame: 7 time points: just after ICU admission and on the days 1,2,3,4,5 and 6 after ICU admission.
Xanthohumol as an adjunctive treatment affects plasma syndecan 1 concentration.
Time frame: 7 time points: just after ICU admission and on the days 1,2,3,4,5 and 6 after ICU admission.
Xanthohumol as an adjunctive treatment affects plasma vascular endothelial adhesion molecule 1 concentration.
Time frame: 7 time points: just after ICU admission and on the days 1,2,3,4,5 and 6 after ICU admission.
Xanthohumol as an adjunctive treatment affects plasma E-selectin concentration.
Time frame: 7 time points: just after ICU admission and on the days 1,2,3,4,5 and 6 after ICU admission.
Xanthohumol as an adjunctive treatment affects plasma vascular endothelial growth factor concentration.
Time frame: 7 time points: just after ICU admission and on the days 1,2,3,4,5 and 6 after ICU admission.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jul 2025.
- Results publication: PubMed 24329115Bartmanska A, Tronina T, Poplonski J, Huszcza E. Biotransformations of prenylated hop flavonoids for drug discovery and production. Curr Drug Metab. 2013 Dec;14(10):1083-97. doi: 10.2174/1389200214666131211151855.
- Results publication: PubMed 23036432Bosmann M, Ward PA. The inflammatory response in sepsis. Trends Immunol. 2013 Mar;34(3):129-36. doi: 10.1016/j.it.2012.09.004. Epub 2012 Oct 2.
- Results publication: PubMed 33517187Chen X, Li Z, Hong H, Wang N, Chen J, Lu S, Zhang H, Zhang X, Bei C. Xanthohumol suppresses inflammation in chondrocytes and ameliorates osteoarthritis in mice. Biomed Pharmacother. 2021 May;137:111238. doi: 10.1016/j.biopha.2021.111238. Epub 2021 Jan 28.
- Results publication: PubMed 36378586Corrado C, Barreca MM, Raimondo S, Diana P, Pepe G, Basilicata MG, Conigliaro A, Alessandro R. Nobiletin and xanthohumol counteract the TNFalpha-mediated activation of endothelial cells through the inhibition of the NF-kappaB signaling pathway. Cell Biol Int. 2023 Mar;47(3):634-647. doi: 10.1002/cbin.11963. Epub 2022 Nov 15.
- Results publication: PubMed 24200239Costa R, Negrao R, Valente I, Castela A, Duarte D, Guardao L, Magalhaes PJ, Rodrigues JA, Guimaraes JT, Gomes P, Soares R. Xanthohumol modulates inflammation, oxidative stress, and angiogenesis in type 1 diabetic rat skin wound healing. J Nat Prod. 2013 Nov 22;76(11):2047-53. doi: 10.1021/np4002898. Epub 2013 Nov 7.
- Results publication: PubMed 36508996Dabrowski W, Gagos M, Siwicka-Gieroba D, Piechota M, Siwiec J, Bielacz M, Kotfis K, Stepulak A, Grzycka-Kowalczyk L, Jaroszynski A, Malbrain ML. Humulus lupus extract rich in xanthohumol improves the clinical course in critically ill COVID-19 patients. Biomed Pharmacother. 2023 Feb;158:114082. doi: 10.1016/j.biopha.2022.114082. Epub 2022 Dec 9.
- Results publication: PubMed 33231055Dartiguelongue JB. Systemic inflammation and sepsis. Part I: Storm formation. Arch Argent Pediatr. 2020 Dec;118(6):e527-e535. doi: 10.5546/aap.2020.eng.e527. English, Spanish.
- Results publication: PubMed 21659748Chong DLW, Sriskandan S. Pro-inflammatory mechanisms in sepsis. Contrib Microbiol. 2011;17:86-107. doi: 10.1159/000324022. Epub 2011 Jun 9.
- Results publication: PubMed 37520007Gaudette S, Smart L, Woodward AP, Sharp CR, Hughes D, Bailey SR, Dandrieux JRS, Santos L, Boller M. Biomarkers of endothelial activation and inflammation in dogs with organ dysfunction secondary to sepsis. Front Vet Sci. 2023 Jul 13;10:1127099. doi: 10.3389/fvets.2023.1127099. eCollection 2023.
- Results publication: PubMed 34170599Girisa S, Saikia Q, Bordoloi D, Banik K, Monisha J, Daimary UD, Verma E, Ahn KS, Kunnumakkara AB. Xanthohumol from Hop: Hope for cancer prevention and treatment. IUBMB Life. 2021 Aug;73(8):1016-1044. doi: 10.1002/iub.2522. Epub 2021 Jul 6.
- Results publication: PubMed 35857130Jung F, Staltner R, Tahir A, Baumann A, Burger K, Halilbasic E, Hellerbrand C, Bergheim I. Oral intake of xanthohumol attenuates lipoteichoic acid-induced inflammatory response in human PBMCs. Eur J Nutr. 2022 Dec;61(8):4155-4166. doi: 10.1007/s00394-022-02964-2. Epub 2022 Jul 20.
- Results publication: PubMed 21093515Lee IS, Lim J, Gal J, Kang JC, Kim HJ, Kang BY, Choi HJ. Anti-inflammatory activity of xanthohumol involves heme oxygenase-1 induction via NRF2-ARE signaling in microglial BV2 cells. Neurochem Int. 2011 Feb;58(2):153-60. doi: 10.1016/j.neuint.2010.11.008. Epub 2010 Nov 18.
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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.
Wojciech Dabrowski, Prof study chair
Medical University of Lublin, Poland
Wlodzimierz Plotek principal investigator
Medical University of Lublin, Poland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Xanthohumol in people with Septic Shock and Pneumonia, run by Medical University of Lublin at 1 site in Poland.
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 6 inclusion and 3 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: looking for participants now, as of the sponsor's last update on 4 Jul 2025. 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 Poland. 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 phase mean?
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Wojciech Dabrowski, Prof (+48604241040, wojciech.dabrowski@umlub.pl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Xanthohumol as an adjunctive treatment improves clinical course in ill septic shock patents (time frame: 7 and 28 days mortality). The study lists 3 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 NCT06225258, which also lists 22 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 4 Jul 2025.