Xanthohumol As an Adjuvant in the Treatment of Septic Shock

Phase 2

Recruiting

• Conditions: Septic Shock; Pneumonia; ARDS
• Interventions: Dietary Supplement: Xanthohumol

• Registration Number: NCT06225258
• Lead Sponsor: Medical University of Lublin

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2023-01-09
• Study First Submitted: 2023-12-21
• Study First Submitted QC: 2024-01-17
• Study First Posted: 2024-01-25
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-23
• Last Update Posted: 2024-12-27
• Primary Completion: 2025-06-30
• Study Completion: 2025-10-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

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

Read More

Exclusion Criteria

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group Xn	Xanthohumol	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.

Primary Outcome Measures

Name	Time	Method
Xanthohumol as an adjunctive treatment improves clinical course in ill septic shock patents	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 treatment affects sepsis-related glycocalyx injury	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.
Xanthohumol as an adjunctive treatmenty affects a severity of inflammation	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.

Secondary Outcome Measures

Name	Time	Method
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.	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.
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.	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.
Xanthohumol as an adjunctive treatment affects plasma syndecan 1 concentration.	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.
Xanthohumol as an adjunctive treatment affects plasma vascular endothelial adhesion molecule 1 concentration.	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.
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.	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.
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.	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.
Xanthohumol as an adjunctive treatment affects plasma E-selectin concentration.	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.
Xanthohumol as an adjunctive treatment affects plasma vascular endothelial growth factor concentration.	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.

Trial Locations

Locations (1)

Intensive Care Unit, University Hospital No 4,; 🇵🇱 Lublin, Poland