Xanthohumol as an Adjuvant in the Treatment of Septic Shock

July 1, 2025 updated by: Medical University of Lublin

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Poland
      • Lublin, Poland, 20-954
        • Recruiting
        • Intensive Care Unit, University Hospital No 4,
        • Sub-Investigator:
          • Wlodzimierz Plotek, Prof MD, PhD
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • lack of agreement
  • septic shock treated for more than 1 day,
  • history of severe chronic cardiac, pulmonary and/or liver diseases

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Group C
Patients are treated according to the recommendations of the Surviving Sepsis Campaign.
Experimental: Group Xn
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.
Dietary supplement: Xanthohumol
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.
Other Names:
  • ChmielXnActive (Salutis Pharmacy, Poland)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
7 and 28 days mortality
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.
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
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.
7 time points: just after ICU admission and on the days 1,2,3,4,5 and 6 after ICU admission.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
7 time points: just after ICU admission and on the days 1,2,3,4,5 and 6 after ICU admission.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical University of Lublin

Investigators

  • Study Chair: Wojciech Dabrowski, Prof, Medical University of Lublin, Poland
  • Principal Investigator: Wlodzimierz Plotek, Medical University of Lublin, Poland

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 9, 2023

Primary Completion (Estimated)

October 30, 2025

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

December 21, 2023

First Submitted That Met QC Criteria

January 17, 2024

First Posted (Actual)

January 25, 2024

Study Record Updates

Last Update Posted (Actual)

July 4, 2025

Last Update Submitted That Met QC Criteria

July 1, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SEPXN

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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