Effect of Adjunctive Ursodeoxycholic Acid on Oxidative Stress, Inflammation, and Organ Dysfunction in Adults With Sepsis
Effect of Adjunctive Ursodeoxycholic Acid on Oxidative Stress, Inflammation, and Organ Dysfunction in Adults With Sepsis: A Randomized Open-Label, Blinded-Endpoint Trial
epsis is a life-threatening syndrome characterized by acute organ dysfunction resulting from a dysregulated host response to infection. Despite advances in antimicrobial therapy, source control, hemodynamic resuscitation, and organ-supportive strategies, sepsis continues to be associated with substantial morbidity and mortality. Current management is primarily supportive and does not directly target the interconnected processes of excessive inflammation, oxidative stress, endothelial dysfunction, and cellular injury that contribute to progressive organ dysfunction. Current international guidance emphasizes prompt antimicrobial therapy, source control, hemodynamic resuscitation, lactate assessment, and appropriate organ support as the foundation of management.
Oxidative stress is an important component of sepsis pathophysiology. Excessive production of reactive oxygen species, together with impaired endogenous antioxidant defenses, can promote lipid peroxidation, mitochondrial dysfunction, cellular injury, and amplification of inflammatory signaling. Maladaptive activation of inflammatory pathways, including nuclear factor-kappa B (NF-κB), contributes to increased production of pro-inflammatory mediators such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). These processes may contribute to dysfunction of the kidney, liver, lungs, cardiovascular system, and other organs.
Ursodeoxycholic acid (UDCA) is a hydrophilic endogenous bile acid with an established clinical safety record and established hepatobiliary therapeutic use. Beyond its conventional hepatoprotective effects, experimental evidence suggests that UDCA may exert antioxidant, anti-inflammatory, anti-apoptotic, cytoprotective, and mitochondrial effects.
The rationale for investigating UDCA in sepsis is supported by several lines of evidence. Experimental work has demonstrated that UDCA can attenuate sepsis-induced acute kidney injury through activation of the Nrf2/HO-1 antioxidant pathway and inhibition of NF-κB signaling, accompanied by reductions in TNF-α, IL-1β, IL-6, and renal injury markers. Experimental studies have also demonstrated attenuation of sepsis-associated lung injury, pulmonary barrier dysfunction, oxidative stress, inflammatory cytokine production, and PANoptosis following UDCA administration.
Importantly, emerging clinical evidence has begun to investigate UDCA in adult sepsis. A retrospective matched study of critically ill adults with sepsis/septic shock did not demonstrate significant improvement in day-3 SOFA score or vasopressor requirements, although improvement in the PaO₂/FiO₂ ratio and earlier extubation were observed among UDCA recipients. More recently, a small prospective pilot involving eight septic patients receiving UDCA explored its potential effects on sepsis-associated platelet dysfunction, while mechanistic studies implicated TREM2-linked signaling.
Therefore, a randomized controlled trial is warranted to determine whether adjunctive UDCA can modify the biological abnormalities underlying sepsis, particularly oxidative stress and inflammation, and whether these effects are accompanied by improvement in organ dysfunction.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 3
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age ≥18 years.
- Confirmed or strongly suspected bacterial, viral, fungal, or other infectious --disease.
- Diagnosis of sepsis according to Sepsis-3 criteria.
Exclusion Criteria:
- Known hypersensitivity to UDCA.
- Pregnancy or breastfeeding.
Study Plan
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 |
|---|---|
|
Active Comparator: UDCA
|
Ursodeoxycholic acid 10-15 mg/kg/day |
|
Other: CONTROL
standard medical treatment of sepsis |
placebo |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Absolute change in serum MDA concentration from baseline to day 5.
Time Frame: 7 days
|
7 days
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- UDCA in Sepsis
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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.