Hepatic EncephalopathyPhase 2/3VSL#3NCT01110447
Secondary Prophylaxis of Hepatic Encephalopathy With a Probiotic Preparation
A Phase 2/3 study testing VSL#3 in people with Hepatic Encephalopathy, run by CD Pharma India Pvt. Ltd. at 1 site in India.
Trial summary
The aim of the proposed project is to study the effects of a probiotic preparation (VSL#3®) for the prevention of recurrence of HE (Hepatic encephalopathy) in patients after the recovery of an episode of overt HE (secondary prophylaxis) Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hepatic Encephalopathy
- What is being tested?
- VSL#3
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 130 participants
- Where
- 1 siteIndia
- Study dates
- Apr 2010to Mar 2013
- Phase
- Phase 2/3
- 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
- Patients diagnosed as having cirrhosis of liver at the Inpatient/Outpatient Liver Clinic of Department of Hepatology, PGIMER, Chandigarh, will be candidates for enrollment.
- The diagnosis of cirrhosis of liver will be based on clinical, biochemical, and ultrasonographical or liver histological data.
Who cannot join
- Alcohol intake during the past 6 weeks
- Hepatocellular carcinoma
- Previous transjugular intrahepatic portosystemic shunt or shunt surgery
- Significant comorbid illness such as heart, respiratory, or renal failure
- Any neurologic diseases such as Alzheimer's disease, Parkinson's disease, and nonhepatic metabolic encephalopathies.
- Patients on psychoactive drugs, such as antidepressants or sedatives
- Those who restart alcohol consumption during follow-up will also be excluded.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Secondary Prophylaxis of Hepatic Encephalopathy: A Double Blind, Randomized, Placebo Controlled Study With Supplementation With a Probiotic Preparation
The aim of the proposed project is to study the effects of a probiotic preparation (VSL#3®) for the prevention of recurrence of HE (Hepatic encephalopathy) in patients after the recovery of an episode of overt HE (secondary prophylaxis)
Read the detailed description
Hepatic encephalopathy (HE) represents a spectrum of neuropsychiatric abnormalities seen in patients with liver dysfunction after exclusion of other known brain disease. The Working Party at the 11th World Congress of Gastroenterology, Vienna proposed a multi-axial definition of HE that defined both, the type of hepatic abnormality (type A, B or C) and the duration/characteristics of neurological manifestations (episodic, persistent or minimal HE) in chronic liver disease. Overt hepatic encephalopathy occurs in 30%-45% of cirrhotic patients and 10%-50% of patients with transjugular intrahepatic portosystemic shunt. Development of HE is associated with a poor prognosis. Bustamante et al reported the survival probability of 42% at 1 year of follow-up and 23% at 3 years in patients with cirrhosis with a first episode of acute HE. The primary treatment of HE is the identification and treatment of the precipitating factors. The majority of the drugs used in the treatment of HE are primarily directed at the reduction or elimination of the increased neurotoxic ammonia levels. A meta-analysis of 22 randomized trials highlighted the lack of data supporting the efficacy of nonabsorbable disaccharides; however, the investigators concluded that current evidence is insufficient to support or refute the use of nonabsorbable disaccharides for treatment of HE. Recent studies with well defined groups however demonstrated the efficacy of lactulose. Alternative therapies such as benzodiazepine receptor antagonists, branched-chain amino acids, and L-ornithine-L-aspartate also have been shown to have some role. Antibiotics are effective in the treatment of HE, but adverse effects and concerns about long-term safety have limited their widespread use. Probiotics may have multiple beneficial effects in the prevention and/or treatment of HE. All four published studies on the effect of probiotics on hepatic encephalopathy have demonstrated efficacy. Treating patients to prevent development of a first episode is classified as primary prophylaxis of HE and preventing recurrence of HE in patients who had a previous episode of HE as secondary prophylaxis of HE. Sharma et al recently demonstrated that lactulose is effective in secondary prevention of HE. This study will assess the effects of a probiotic preparation for the prevention of recurrence of HE (secondary prophylaxis) in patients after the recovery of an episode of overt HE.
- Conditions
- Hepatic Encephalopathy
- Being tested
- VSL#3, Placebo
- Keywords
- Hepatic Encephalopathy, probiotics
- Medical subject headings
- Hepatic Encephalopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VSL#3Drug
Also called Probiotic
VSL#3® is made up of 4 strains of Lactobacilli (L. paracasei, L. plantarum, L. acidophilus and L. delbrueckii subsp. bulgaricus), 3 strains of Bifidobacteria (B. longum, B. infantis, B. breve) and 1 strain of Streptococcus thermophilus. Dose would be 1 sachet per day (Each sachet containing 900 Billion CFU). The duration of treatment would be for 24 weeks
PlaceboOther
Also called Dummy Preparation
Placebo sachets contain corn starch. Dose: 1 sachet per day Duration of treatment: 24 weeks
| Study group | Role | What they receive |
|---|---|---|
| VSL#3 | Experimental | VSL#3® is made up of 4 strains of Lactobacilli (L. paracasei, L. plantarum, L. acidophilus and L. delbrueckii subsp. bulgaricus), 3 strains of Bifidobacteria (B. longum, B. infantis, B. breve) and 1 strain of Streptococcus thermophilus. Receives: Drug: VSL#3 |
| Placebo | Placebo comparator | Placebo sachets contain corn starch Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary end point will be development of overt HE or completion of a follow-up of 6 months after enrollment
Measured: 6 months after enrollment
Secondary outcomes (1)
Improvement in liver functions (Child and MELD score), psychometry (psychometric hepatic encephalopathy score), blood ammonia, blood cytokines level and survival time after medication
Measured: 6 months after enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2010 (estimated)
- Study startApr 2010
- Primary completionMar 2013
- Study completionMar 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hepatic EncephalopathyStudies 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 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 130 participants (actual)
Sponsor and investigators
- Lead sponsor
- CD Pharma India Pvt. Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Post Graduate Institute of Medical Education and Research, Chandigarh
- Responsible party
- Sponsor
- Investigators
- Radha K Dhiman, MD,DM,MNAMS, Principal investigator, Postgraduate Institute of Medical Education & Research (PGIMER)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01110447
- Sponsor's protocol ID
- MHE2-VSL#3-Ver3_30032010
- Acronym
- VSL#3
- Status last verified
- Dec 2013
- First submitted
- 23 Apr 2010
- Last updated
- 30 Dec 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Dhiman RK, Grover GS, Premkumar M, Roy A, Taneja S, Duseja A, Arora S; MMPHCRF Investigators. Outcomes of Real-World Integrated HCV Microelimination for People Who Inject Drugs: An expansion of the Punjab Model. EClinicalMedicine. 2021 Oct 17;41:101148. doi: 10.1016/j.eclinm.2021.101148. eCollection 2021 Nov.
PubMed 34712928Dhiman RK, Grover GS, Premkumar M, Taneja S, Duseja A, Arora S, Rathi S, Satsangi S, Roy A; MMPHCRF Investigators. Decentralized care with generic direct-acting antivirals in the management of chronic hepatitis C in a public health care setting. J Hepatol. 2019 Dec;71(6):1076-1085. doi: 10.1016/j.jhep.2019.07.006. Epub 2019 Jul 17.
PubMed 31325468Dhiman RK, Rana B, Agrawal S, Garg A, Chopra M, Thumburu KK, Khattri A, Malhotra S, Duseja A, Chawla YK. Probiotic VSL#3 reduces liver disease severity and hospitalization in patients with cirrhosis: a randomized, controlled trial. Gastroenterology. 2014 Dec;147(6):1327-37.e3. doi: 10.1053/j.gastro.2014.08.031. Epub 2014 Aug 27.
PubMed 25450083
Study at a glance
From the registry record, last updated by the sponsor on 30 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Secondary Prophylaxis of Hepatic Encephalopathy: A Double Blind, Randomized, Placebo Controlled Study With Supplementation With a Probiotic Preparation
- ClinicalTrials.gov ID
- NCT01110447
- Acronym / sponsor ID
- VSL#3 / MHE2-VSL#3-Ver3_30032010
- Conditions
- Hepatic Encephalopathy
- Keywords
- Hepatic Encephalopathy, probiotics
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 130 participants (actual)
- Lead sponsor
- CD Pharma India Pvt. Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Post Graduate Institute of Medical Education and Research, Chandigarh
- Study start
- Apr 2010
- Primary completion
- Mar 2013 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 26 Apr 2010 (estimated)
- 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.
The aim of the proposed project is to study the effects of a probiotic preparation (VSL#3®) for the prevention of recurrence of HE (Hepatic encephalopathy) in patients after the recovery of an episode of overt HE (secondary prophylaxis)
Detailed description
Hepatic encephalopathy (HE) represents a spectrum of neuropsychiatric abnormalities seen in patients with liver dysfunction after exclusion of other known brain disease. The Working Party at the 11th World Congress of Gastroenterology, Vienna proposed a multi-axial definition of HE that defined both, the type of hepatic abnormality (type A, B or C) and the duration/characteristics of neurological manifestations (episodic, persistent or minimal HE) in chronic liver disease. Overt hepatic encephalopathy occurs in 30%-45% of cirrhotic patients and 10%-50% of patients with transjugular intrahepatic portosystemic shunt. Development of HE is associated with a poor prognosis. Bustamante et al reported the survival probability of 42% at 1 year of follow-up and 23% at 3 years in patients with cirrhosis with a first episode of acute HE. The primary treatment of HE is the identification and treatment of the precipitating factors. The majority of the drugs used in the treatment of HE are primarily directed at the reduction or elimination of the increased neurotoxic ammonia levels. A meta-analysis of 22 randomized trials highlighted the lack of data supporting the efficacy of nonabsorbable disaccharides; however, the investigators concluded that current evidence is insufficient to support or refute the use of nonabsorbable disaccharides for treatment of HE. Recent studies with well defined groups however demonstrated the efficacy of lactulose. Alternative therapies such as benzodiazepine receptor antagonists, branched-chain amino acids, and L-ornithine-L-aspartate also have been shown to have some role. Antibiotics are effective in the treatment of HE, but adverse effects and concerns about long-term safety have limited their widespread use. Probiotics may have multiple beneficial effects in the prevention and/or treatment of HE. All four published studies on the effect of probiotics on hepatic encephalopathy have demonstrated efficacy. Treating patients to prevent development of a first episode is classified as primary prophylaxis of HE and preventing recurrence of HE in patients who had a previous episode of HE as secondary prophylaxis of HE. Sharma et al recently demonstrated that lactulose is effective in secondary prevention of HE. This study will assess the effects of a probiotic preparation for the prevention of recurrence of HE (secondary prophylaxis) in patients after the recovery of an episode of overt HE.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| VSL#3 | Experimental | Drug: VSL#3VSL#3® is made up of 4 strains of Lactobacilli (L. paracasei, L. plantarum, L. acidophilus and L. delbrueckii subsp. bulgaricus), 3 strains of Bifidobacteria (B. longum, B. infantis, B. breve) and 1 strain of Streptococcus thermophilus. |
| Placebo | Placebo comparator | Other: PlaceboPlacebo sachets contain corn starch |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients diagnosed as having cirrhosis of liver at the Inpatient/Outpatient Liver Clinic of Department of Hepatology, PGIMER, Chandigarh, will be candidates for enrollment.
- The diagnosis of cirrhosis of liver will be based on clinical, biochemical, and ultrasonographical or liver histological data.
Key exclusion criteria (7 listed)
- Alcohol intake during the past 6 weeks
- Hepatocellular carcinoma
- Previous transjugular intrahepatic portosystemic shunt or shunt surgery
- Significant comorbid illness such as heart, respiratory, or renal failure
- Any neurologic diseases such as Alzheimer's disease, Parkinson's disease, and nonhepatic metabolic encephalopathies.
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 |
|---|---|---|
| VSL#3Also: ProbioticVSL#3® is made up of 4 strains of Lactobacilli (L. paracasei, L. plantarum, L. acidophilus and L. delbrueckii subsp. bulgaricus), 3 strains of Bifidobacteria (B. longum, B. infantis, B. breve) and 1 strain of Streptococcus thermophilus. Dose would be 1 sachet per day (Each sachet containing 900 Billion CFU). The duration of treatment would be for 24 weeks | Drug | VSL#3 |
| PlaceboAlso: Dummy PreparationPlacebo sachets contain corn starch. Dose: 1 sachet per day Duration of treatment: 24 weeks | Other | Placebo |
Primary outcome
The primary end point will be development of overt HE or completion of a follow-up of 6 months after enrollment
Time frame: 6 months after enrollment
1 secondary outcome
Improvement in liver functions (Child and MELD score), psychometry (psychometric hepatic encephalopathy score), blood ammonia, blood cytokines level and survival time after medication
Time frame: 6 months after enrollment
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 30 Dec 2013.
- Derived from this study: PubMed 34712928Dhiman RK, Grover GS, Premkumar M, Roy A, Taneja S, Duseja A, Arora S; MMPHCRF Investigators. Outcomes of Real-World Integrated HCV Microelimination for People Who Inject Drugs: An expansion of the Punjab Model. EClinicalMedicine. 2021 Oct 17;41:101148. doi: 10.1016/j.eclinm.2021.101148. eCollection 2021 Nov.
- Derived from this study: PubMed 31325468Dhiman RK, Grover GS, Premkumar M, Taneja S, Duseja A, Arora S, Rathi S, Satsangi S, Roy A; MMPHCRF Investigators. Decentralized care with generic direct-acting antivirals in the management of chronic hepatitis C in a public health care setting. J Hepatol. 2019 Dec;71(6):1076-1085. doi: 10.1016/j.jhep.2019.07.006. Epub 2019 Jul 17.
- Derived from this study: PubMed 25450083Dhiman RK, Rana B, Agrawal S, Garg A, Chopra M, Thumburu KK, Khattri A, Malhotra S, Duseja A, Chawla YK. Probiotic VSL#3 reduces liver disease severity and hospitalization in patients with cirrhosis: a randomized, controlled trial. Gastroenterology. 2014 Dec;147(6):1327-37.e3. doi: 10.1053/j.gastro.2014.08.031. Epub 2014 Aug 27.
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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.
Radha K Dhiman, MD,DM,MNAMS principal investigator
Postgraduate Institute of Medical Education & Research (PGIMER)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing VSL#3 in people with Hepatic Encephalopathy, run by CD Pharma India Pvt. Ltd. at 1 site in India.
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 2 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 30 Dec 2013. 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 India. 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.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 primary end point will be development of overt HE or completion of a follow-up of 6 months after enrollment (time frame: 6 months after enrollment). 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 NCT01110447, which also lists 3 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 30 Dec 2013.