Xanthohumol as an Adjuvant in the Treatment of Septic Shock

Medical University of Lublin

Status and phase: Enrolling; Phase 2

Conditions: Pneumonia; ARDS; Septic Shock

Treatments: Dietary Supplement: Xanthohumol

Study type: Interventional

Funder types: Other

Identifiers

NCT06225258

SEPXN

Details and patient eligibility

About

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.

Enrollment: 50 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

---

50 participants in 2 patient groups

Group C

No Intervention group

Description:

Patients are treated according to the recommendations of the Surviving Sepsis Campaign.

Group Xn

Experimental group

Description:

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.

Treatment:

Dietary Supplement: Xanthohumol