Probiotics and Hemodynamic Changes in Cirrhosis

Cirrhosis Clinical Trial

— PrBHCCir  

Official title:

The Effect of Probiotics on Hemodynamic Changes and Complications of Cirrhosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05231772
• Other study ID #: 2533644
• Status: Completed
• Phase: N/A
• Start date: March 1, 2021
• Est. completion date: March 29, 2022

Study information

• Verified date: January 2022
• Source: I.M. Sechenov First Moscow State Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: March 29, 2022
• Est. primary completion date: March 29, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cirrhosis
• Fibrosis
• Liver Cirrhosis

Intervention

Drug:
• Saccharomyces Boulardii Probiotic Supplement
Probiotic yeast
• Placebo
Placebo

Locations

Country	Name	City	State
Russian Federation	Clinic for Internal Diseases, Gastroenterology and Hepatology at Sechenov University	Moscow

Sponsors (1)

Lead Sponsor	Collaborator
I.M. Sechenov First Moscow State Medical University

Country where clinical trial is conducted

Russian Federation, 

References & Publications (4)

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. 2021 Oct 13. doi: 10.1007/s12602-021-09858-5. [Epub ahead of print] — View 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. — View 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. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the change in cardiac output	Transthoracic echocardiography (with Acuson S2000 by Siemens Ltd, USA, registration number 2017/6109 from 24.07.2018) according to the guidelines of the American Society of Echocardiography (published in 2015) with a simultaneous assessment of blood pressure (with semi-automatic tonometer UA-604 by AND Ltd, Japan, registration number 2011/09642 from 10.10.2018) and heart rate will be performed to assess systemic hemodynamics. Cardiac output will be calculated as (stroke volume) × (heart rate).	at inclusion and 3 months after the start of the study
Primary	the change in number of points on the Child-Pugh scale	The scale assesses the degree of hyperbilirubinemia (1 point - serum total bilirubin level is less than 2 mg / dl, 2 points - 2-3 mg / dl, 3 points - above 3 mg / dl), hypoalbuminemia (1 point - serum albumin level above 35 g / l, 2 points - 28-35 g / l, 3 points - less than 28 g / l), hypocoagulation (1 point - international normalized ratio less than 1.7, 2 points - 1.7-2.3, 3 points - above 2.3) degree of ascites (1 points - no ascites, 2 points - ascites detected only with ultrasound, 3 points - large ascites visible to the eyes) of hepatic encephalopathy (1 point - no hepatic encephalopathy; 2 points - hepatic encephalopathy without severe manifestations (stupor or coma); 3 points - severe hepatic encephalopathy (stupor or coma)).	at inclusion and 3 months after the start of the study
Secondary	the change in the serum albumin level	venous blood will be take on an empty stomach at 7-9 am without any special preparation	at inclusion and 3 months after the start of the study
Secondary	the change in the serum total bilirubin level	venous blood will be take on an empty stomach at 7-9 am without any special preparation	at inclusion and 3 months after the start of the study
Secondary	the change in the international normalized ratio	venous blood will be take on an empty stomach at 7-9 am without any special preparation	at inclusion and 3 months after the start of the study
Secondary	the change in the serum C-reactive protein level	venous blood will be take on an empty stomach at 7-9 am without any special preparation	at inclusion and 3 months after the start of the study
Secondary	the change in systemic vascular resistance	systemic vascular resistance will be calculated as mean arterial pressure/cardiac output	at inclusion and 3 months after the start of the study
Secondary	the change in the degree of hepatic encephalopathy	0 - no hepatic encephalopathy, 1 - minimal hepatic encephalopathy (normal neurological status but abnormal number connection test), 2 - overt hepatic encephalopathy (abnormal neurological status)	at inclusion and 3 months after the start of the study
Secondary	the change in the degree of ascites	0 points - no ascites, 1 points - ascites detected only with ultrasound, 2 points - ascites detected with the shifting dullness method; 3 point - gross refractory ascites.	at inclusion and 3 months after the start of the study
Secondary	the change in the presence of small intestinal bacterial overgrowth	lactulose hydrogene breath test with Gastro+Gastrolyzer (by Bedfont Ltd, the United kingdom, registration number 2010/06253 from 17.09.2020) in accordance with the North American Consensus: the presence of small intestinal bacterial overgrowth is considered when there was an increase in breath hydrogen of at least 20 ppm above the baseline value within 90 minutes after taking 10 ml of lactulose dissolved in 200 ml of water.	at inclusion and 3 months after the start of the study
Secondary	the change in the serum presepsin level	venous blood will be take on an empty stomach at 7-9 am without any special preparation	at inclusion and 3 months after the start of the study
Secondary	the change in the serum lipopolysaccharide level	venous blood will be take on an empty stomach at 7-9 am without any special preparation	at inclusion and 3 months after the start of the study
Secondary	the change in the serum claudin 3 level	venous blood will be take on an empty stomach at 7-9 am without any special preparation	at inclusion and 3 months after the start of the study
Secondary	the change in the serum tumor necrosis factor alpha level	venous blood will be take on an empty stomach at 7-9 am without any special preparation	at inclusion and 3 months after the start of the study
Secondary	the change in the serum nitrites level	venous blood will be take on an empty stomach at 7-9 am without any special preparation	at inclusion and 3 months after the start of the study
Secondary	the change in the serum big endothelin level	venous blood will take on an empty stomach at 7-9 am without any special preparation	at inclusion and 3 months after the start of the study