CirrhosisPrBHCCirNCT05231772
Probiotics and Hemodynamic Changes in Cirrhosis
A study testing Saccharomyces Boulardii Probiotic Supplement in people with Cirrhosis, run by I.M. Sechenov First Moscow State Medical University at 1 site in Russia.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Cirrhosis
- What is being tested?
- Saccharomyces Boulardii Probiotic Supplement
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteRussia
- Study dates
- 1 Mar 2021to 29 Mar 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Cirrhosis
- Child-Pugh class B or C;
- Age between 18 and 70 years;
- Signed informed consent.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Russia1 site
Clinic for Internal Diseases, Gastroenterology and Hepatology at Sechenov University
Moscow, 119435
About this study
Official title: The Effect of Probiotics on Hemodynamic Changes and Complications of Cirrhosis
This is a single-center blinded randomized interventional placebo-controlled study of the effect of probiotics on hemodynamic parameters and liver function in cirrhosis.
Read the 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.
- Conditions
- Cirrhosis
- Being tested
- Saccharomyces Boulardii Probiotic Supplement, Placebo
- Keywords
- gut-liver axis, microbiota, microbiome, liver, cirrhosis, hemodynamics
- Medical subject headings
- Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Saccharomyces Boulardii Probiotic SupplementDrug
Also called Probiotics, Enterol
Probiotic yeast
PlaceboDrug
Also called No other name
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Probiotics | Experimental | Patients in the Test arm will receive Saccharomyces boulardii (Saccharomyces), (Enterol), Biocodex Ltd, France, registration number LP-000622 from 21.09.2011 at a dose of 250 mg 2 times a day for 3 months. Receives: Drug: Saccharomyces Boulardii Probiotic Supplement |
| Placebo | Placebo comparator | Patients in the Placebo arm will receive the placebo at a dose of 250 mg 2 times a day for 3 months. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: at inclusion and 3 months after the start of the study
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)).
Measured: at inclusion and 3 months after the start of the study
Secondary outcomes (14)
the change in the serum albumin level
venous blood will be take on an empty stomach at 7-9 am without any special preparation
Measured: at inclusion and 3 months after the start of the study
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
Measured: at inclusion and 3 months after the start of the study
the change in the international normalized ratio
venous blood will be take on an empty stomach at 7-9 am without any special preparation
Measured: at inclusion and 3 months after the start of the study
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
Measured: at inclusion and 3 months after the start of the study
the change in systemic vascular resistance
systemic vascular resistance will be calculated as mean arterial pressure/cardiac output
Measured: at inclusion and 3 months after the start of the study
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)
Measured: at inclusion and 3 months after the start of the study
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.
Measured: at inclusion and 3 months after the start of the study
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.
Measured: at inclusion and 3 months after the start of the study
the change in the serum presepsin level
venous blood will be take on an empty stomach at 7-9 am without any special preparation
Measured: at inclusion and 3 months after the start of the study
the change in the serum lipopolysaccharide level
venous blood will be take on an empty stomach at 7-9 am without any special preparation
Measured: at inclusion and 3 months after the start of the study
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
Measured: at inclusion and 3 months after the start of the study
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
Measured: at inclusion and 3 months after the start of the study
the change in the serum nitrites level
venous blood will be take on an empty stomach at 7-9 am without any special preparation
Measured: at inclusion and 3 months after the start of the study
the change in the serum big endothelin level
venous blood will take on an empty stomach at 7-9 am without any special preparation
Measured: at inclusion and 3 months after the start of the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2022
- Study start1 Mar 2021
- Primary completion29 Mar 2022
- Study completion29 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for CirrhosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- I.M. Sechenov First Moscow State Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vladimir Ivashkin, Prof., Principal investigator, I.M. Sechenov First Moscow State Medical University (Sechenov University)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05231772
- Sponsor's protocol ID
- 2533644
- Acronym
- PrBHCCir
- Status last verified
- Jan 2022
- First submitted
- 27 Jan 2022
- Last updated
- 31 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Data disclosure is not permitted by the Local Ethics Committee of I.M. Sechenov First Moscow State Medical University. For more information about the study, you need to contact the principal investigator.
Publications
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.
PubMed 34877269Maslennikov 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.
PubMed 34131470Maslennikov 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.
PubMed 34630882Ivashkin 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.
PubMed 34643888
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Probiotics on Hemodynamic Changes and Complications of Cirrhosis
- ClinicalTrials.gov ID
- NCT05231772
- Acronym / sponsor ID
- PrBHCCir / 2533644
- Conditions
- Cirrhosis
- Keywords
- gut-liver axis, microbiota, microbiome, liver, cirrhosis, hemodynamics
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- I.M. Sechenov First Moscow State Medical UniversityUniversity, hospital or other
- Study start
- 1 Mar 2021 (actual)
- Primary completion
- 29 Mar 2022 (actual)
- Study completion
- 29 Mar 2022 (actual)
- First posted
- 9 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Probiotics | Experimental | Drug: Saccharomyces Boulardii Probiotic SupplementPatients in the Test arm will receive Saccharomyces boulardii (Saccharomyces), (Enterol), Biocodex Ltd, France, registration number LP-000622 from 21.09.2011 at a dose of 250 mg 2 times a day for 3 months. |
| Placebo | Placebo comparator | Drug: PlaceboPatients in the Placebo arm will receive the placebo at a dose of 250 mg 2 times a day for 3 months. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Cirrhosis
- Child-Pugh class B or C;
- Age between 18 and 70 years;
- Signed informed consent.
Key exclusion criteria (7 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Saccharomyces Boulardii Probiotic SupplementAlso: Probiotics, EnterolProbiotic yeast | Drug | Probiotics |
| PlaceboAlso: No other namePlacebo | Drug | Placebo |
Primary outcome
the change in cardiac output
Time frame: at inclusion and 3 months after the start of the study
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).
the change in number of points on the Child-Pugh scale
Time frame: at inclusion and 3 months after the start of the study
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)).
14 secondary outcomes
the change in the serum albumin level
Time frame: at inclusion and 3 months after the start of the study
the change in the serum total bilirubin level
Time frame: at inclusion and 3 months after the start of the study
the change in the international normalized ratio
Time frame: at inclusion and 3 months after the start of the study
the change in the serum C-reactive protein level
Time frame: at inclusion and 3 months after the start of the study
the change in systemic vascular resistance
Time frame: at inclusion and 3 months after the start of the study
the change in the degree of hepatic encephalopathy
Time frame: at inclusion and 3 months after the start of the study
the change in the degree of ascites
Time frame: at inclusion and 3 months after the start of the study
the change in the presence of small intestinal bacterial overgrowth
Time frame: at inclusion and 3 months after the start of the study
the change in the serum presepsin level
Time frame: at inclusion and 3 months after the start of the study
the change in the serum lipopolysaccharide level
Time frame: at inclusion and 3 months after the start of the study
the change in the serum claudin 3 level
Time frame: at inclusion and 3 months after the start of the study
the change in the serum tumor necrosis factor alpha level
Time frame: at inclusion and 3 months after the start of the study
the change in the serum nitrites level
Time frame: at inclusion and 3 months after the start of the study
the change in the serum big endothelin level
Time frame: at inclusion and 3 months after the start of the study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2022.
- Background: PubMed 34877269Maslennikov 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.
- Background: PubMed 34131470Maslennikov 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.
- Background: PubMed 34630882Maslennikov 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.
- Background: PubMed 34643888Ivashkin 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.
- Individual participant dataSharing planned: No. Data disclosure is not permitted by the Local Ethics Committee of I.M. Sechenov First Moscow State Medical University. For more information about the study, you need to contact the principal investigator.
Related trials for Cirrhosis
Not yet recruitingObservational study
A Study of Fatigue, Itching and Daily Activities in People With Primary Biliary Cholangitis Starting Elafibranor
Primary Biliary Cholangitis (PBC)
RecruitingPhase 1/2
Nitazoxanide in Spontaneous Bacterial Peritonitis
SBP - Spontaneous Bacterial Peritonitis
RecruitingPhase 3
Fenofibrate for Patients With Primary Biliary Cirrhosis Who Had An Inadequate Response to Ursodeoxycholic Acid
Primary Biliary Cirrhosis
RecruitingPhase 1/2
N-Acetylcysteine in the Management of Spontaneous Bacterial Peritonitis
SBP - Spontaneous Bacterial Peritonitis
RecruitingPhase 2/3
Fenofibrate in Patients With Primary Biliary Cholangitis (PBC)
Primary Biliary Cholangitis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vladimir Ivashkin, Prof. principal investigator
I.M. Sechenov First Moscow State Medical University (Sechenov University)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Saccharomyces Boulardii Probiotic Supplement in people with Cirrhosis, run by I.M. Sechenov First Moscow State Medical University at 1 site in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the change in cardiac output (time frame: at inclusion and 3 months after the start of the study). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05231772, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2022.