Clinical trial NCT05231772: Probiotics and Hemodynamic Changes in Cirrhosis
Official title: The Effect of Probiotics on Hemodynamic Changes and Complications of Cirrhosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cirrhosis
Keywords: gut-liver axis
microbiota
microbiome
liver
cirrhosis
hemodynamics
Lead sponsor: I.M. Sechenov First Moscow State Medical University
Sponsor class: OTHER
First posted: 2022-02-09
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a single-center blinded randomized interventional placebo-controlled study of the effect of probiotics on hemodynamic parameters and liver function in cirrhosis.

Detailed description: Forty patients with Child-Pugh class B and C cirrhosis will be randomized in a 1.5:1 ratio to test and control arms. Patients in the test arm will receive probiotic Saccharomyces boulardii (A07FA02 - Saccharomyces (Enterol) Biocodex Ltd, France, registration number LP-000622 from 21.09.2011) for 3 months, patients in the control arm will receive placebo for 3 months. All patients also will receive standard treatment: spironolactone 100 mg/day in ascites and carvedilol 12.5 mg/day in esophageal varices. The patients will be blinded. At inclusion and after 3 months after starting of probiotic/placebo treatment, systemic hemodynamics parameters (cardiac output and systemic vascular resistance), liver function (serum albumin and total bilirubin level, international normalized ratio, presence and degree of ascites or hepatic encephalopathy), the gut microbiome, biomarkers of bacterial translocation (presepsin, lipopolysaccharide), intestinal permeability (claudin 3), systemic inflammation (tumor necrosis factor alpha ) and endothelial dysfunction (nitrites, endothelin) will be assessed. After the end of the study, an interim analysis of the effect of the probiotic on aforementioned systemic hemodynamics and liver function indicators will be carried out. If there is a positive effect, a full analysis of all the aforementioned factors contributing to its development will be performed.

Eligibility criteria: Inclusion Criteria:

* Cirrhosis
* Child-Pugh class B or C;
* Age between 18 and 70 years;
* Signed informed consent.

Exclusion Criteria:

* Use of lactulose, lactitol, or other prebiotics, probiotics, antibiotics, or metformin in the past 6 weeks before inclusion;
* Alcohol consumption in the past 6 weeks before inclusion;
* Inflammatory bowel disease;
* Cancer;
* Prematurely discontinuation of the consumption of tested probiotic/placebo;
* Started taking antibiotics, other probiotics, or prebiotics during the follow-up period;
* Refusal to participate during the follow-up period.

Primary outcomes:
measure: the change in cardiac output
timeFrame: at inclusion and 3 months after the start of the study
measure: the change in number of points on the Child-Pugh scale
timeFrame: at inclusion and 3 months after the start of the study
Secondary outcomes:
measure: the change in the serum albumin level
timeFrame: at inclusion and 3 months after the start of the study
measure: the change in the serum total bilirubin level
timeFrame: at inclusion and 3 months after the start of the study
measure: the change in the international normalized ratio
timeFrame: at inclusion and 3 months after the start of the study
measure: the change in the serum C-reactive protein level
timeFrame: at inclusion and 3 months after the start of the study
measure: the change in systemic vascular resistance
timeFrame: at inclusion and 3 months after the start of the study
measure: the change in the degree of hepatic encephalopathy
timeFrame: at inclusion and 3 months after the start of the study
measure: the change in the degree of ascites
timeFrame: at inclusion and 3 months after the start of the study
measure: the change in the presence of small intestinal bacterial overgrowth
timeFrame: at inclusion and 3 months after the start of the study
measure: the change in the serum presepsin level
timeFrame: at inclusion and 3 months after the start of the study
measure: the change in the serum lipopolysaccharide level
timeFrame: at inclusion and 3 months after the start of the study
measure: the change in the serum claudin 3 level
timeFrame: at inclusion and 3 months after the start of the study
measure: the change in the serum tumor necrosis factor alpha level
timeFrame: at inclusion and 3 months after the start of the study
measure: the change in the serum nitrites level
timeFrame: at inclusion and 3 months after the start of the study
measure: the change in the serum big endothelin level
timeFrame: at inclusion and 3 months after the start of the study
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Clinic for Internal Diseases, Gastroenterology and Hepatology at Sechenov University
Study officials:
affiliation: I.M. Sechenov First Moscow State Medical University (Sechenov University)
name: Vladimir Ivashkin, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Maslennikov R, Ivashkin V, Efremova I, Poluektova E, Shirokova E. Gut-liver axis in cirrhosis: Are hemodynamic changes a missing link? World J Clin Cases. 2021 Nov 6;9(31):9320-9332. doi: 10.12998/wjcc.v9.i31.9320.
citation: Maslennikov R, Ivashkin V, Efremova I, Alieva A, Kashuh E, Tsvetaeva E, Poluektova E, Shirokova E, Ivashkin K. Gut dysbiosis is associated with poorer long-term prognosis in cirrhosis. World J Hepatol. 2021 May 27;13(5):557-570. doi: 10.4254/wjh.v13.i5.557.
citation: Maslennikov R, Ivashkin V, Efremova I, Poluektova E, Shirokova E. Probiotics in hepatology: An update. World J Hepatol. 2021 Sep 27;13(9):1154-1166. doi: 10.4254/wjh.v13.i9.1154.
citation: Ivashkin V, Fomin V, Moiseev S, Brovko M, Maslennikov R, Ulyanin A, Sholomova V, Vasilyeva M, Trush E, Shifrin O, Poluektova E. Efficacy of a Probiotic Consisting of Lacticaseibacillus rhamnosus PDV 1705, Bifidobacterium bifidum PDV 0903, Bifidobacterium longum subsp. infantis PDV 1911, and Bifidobacterium longum subsp. longum PDV 2301 in the Treatment of Hospitalized Patients with COVID-19: a Randomized Controlled Trial. Probiotics Antimicrob Proteins. 2023 Jun;15(3):460-468. doi: 10.1007/s12602-021-09858-5. Epub 2021 Oct 13.