Xanthohumol as an Adjuvant in the Treatment of Septic Shock

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

Interventions

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.

Sponsors & Collaborators

• Medical University of Lublin

  lead OTHER

Principal Investigators

• Wojciech Dabrowski, Prof · Medical University of Lublin, Poland

• Wlodzimierz Plotek · Medical University of Lublin, Poland

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-01-09

Primary Completion

2025-10-30

Completion

2025-12-31

Countries

• Poland

Study Locations