Xanthohumol as an Adjuvant in the Treatment of Septic Shock

NCT06225258 | Recruiting Phase 2

• 1 other identifier: SEPXN
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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). 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

Keywords

septic shock; inflammation; Xanthohumol; adjuvant; endotheliopathy; ARDS; cytokine

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  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

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

Study Arms (2)

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.

Dietary Supplement: Xanthohumol

Interventions

Xanthohumol DIETARY_SUPPLEMENT

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.

Also known as: ChmielXnActive (Salutis Pharmacy, Poland)

Group Xn

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Medical University of Lublin: lead

Study Sites (1)

Intensive Care Unit, University Hospital No 4,

Lublin, Lublin Voivodeship, 20-954, Poland

RECRUITING

Related Publications (22)

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MeSH Terms

Conditions

Shock, Septic; Pneumonia; Inflammation

Interventions

xanthohumol

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Wojciech Dabrowski, Prof

  Medical University of Lublin, Poland

  STUDY CHAIR

• Wlodzimierz Plotek

  Medical University of Lublin, Poland

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wojciech Dabrowski, Prof

CONTACT

+48604241040; wojciech.dabrowski@umlub.pl

Wojciech Dabrowski

CONTACT

+48604241040; w.dabrowski5@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 21, 2023
• First Posted: January 25, 2024
• Study Start: January 9, 2023
• Primary Completion: October 30, 2025
• Study Completion: December 31, 2025
• Last Updated: July 4, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1)