| CTRI Number |
CTRI/2008/091/000268 [Registered on: 08/12/2008] |
| Last Modified On: |
26/09/2013 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
Type of Study
Modification(s)
|
Probiotic
Preventive |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
Public Title of Study
Modification(s)
|
Probiotic preparation, VSL#3 as a support pharmaceutical therapy in cirrhotic patients for the treatment of minimal hepatic encephalopathy (MHE) |
|
Scientific Title of Study
|
Supplementation with a probiotic preparation, VSL#3® as a support pharmaceutical therapy in cirrhotic patients for the treatment of minimal hepatic encephalopathy (MHE). A double-blind, randomized, placebo controlled study. |
| Trial Acronym |
|
Secondary IDs if Any
Modification(s)
|
| Secondary ID |
Identifier |
| MHE-VSL#3- version 2 – Dated 09-Apr-08 |
Protocol Number |
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)
|
| Name |
Dr R K Dhiman |
| Designation |
Professor |
| Affiliation |
PGIMER |
| Address |
Dept. of Hepatology, PGIMER
Sector-12
Chandigarh
CHANDIGARH
160012
India |
| Phone |
09914209337 |
| Fax |
0172-2744401 |
| Email |
rkpsdhiman@hotmail.com |
|
Details of Contact Person
Scientific Query
Modification(s)
|
| Name |
R K Dhiman |
| Designation |
Professor |
| Affiliation |
PGIMER, Chandigarh |
| Address |
Dept. of Hepatology, PGIMER
Sector-12
Chandigarh
CHANDIGARH
160012
India |
| Phone |
09914209337 |
| Fax |
0172-2744401 |
| Email |
rkpsdhiman@hotmail.com |
|
Details of Contact Person
Public Query
Modification(s)
|
| Name |
R K Dhiman |
| Designation |
Professor |
| Affiliation |
PGIMER, Chandigarh |
| Address |
Dept. of Hepatology, PGIMER
Sector-12
Chandigarh
CHANDIGARH
160012
India |
| Phone |
09914209337 |
| Fax |
0172-2744401 |
| Email |
rkpsdhiman@hotmail.com |
|
|
Source of Monetary or Material Support
|
| CD Pharma India Pvt. Ltd., C-1/53, First Floor, SDA, New Delhi-110016, Tel.:+91-11-41759898 |
|
Primary Sponsor
Modification(s)
|
| Name |
CD Pharma India Pvt Ltd |
| Address |
C-1/53, First Floor, SDA, New delhi-110016 |
| Type of Sponsor |
Pharmaceutical industry-Indian |
|
|
Details of Secondary Sponsor
|
|
Countries of Recruitment
Modification(s)
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr. R K Dhiman |
Dept. of Hepatology |
PGIMER, Sector-12,-160012
Chandigarh
CHANDIGARH |
+91-9914209337
+91-172-2744401
rkpsdhiman@hotmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| IEC, PGIMER |
Approved |
|
Regulatory Clearance Status from DCGI
Modification(s)
|
|
Health Condition / Problems Studied
Modification(s)
|
| Health Type |
Condition |
| Patients |
Cirrhotic patients with Minimal Hepatic encephalopathy , |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Placebo sachets containing corn starch |
1 sachet per day for 16 weeks |
| Intervention |
VSL#3® sachets, each containing 900 billion viable lyophilised bacteria, comprising 4 strains of Lactobacillus (L. paracasei, L. plantarum, L. acidophilus and L. bulgaricus), 3 strains of Bifidobacteria (B. longum, B. breve and B. infantis) and 1 strain of Streptococcus thermophilus |
1 sachet per day for 16 weeks |
|
Inclusion Criteria
Modification(s)
|
| Age From |
16.00 Year(s) |
| Age To |
80.00 Year(s) |
| Gender |
Both |
| Details |
1. Male and female patients aged more than 16 years;
2. Diagnosis of cirrhosis based on standard clinical and biochemical criteria and, possibly, biopsy proven;
3. No long-term antibiotic treatment needed
4. Able to provide written informed consent
|
|
| ExclusionCriteria |
| Details |
1. Alcohol consumption or substance abuse within the last 3 months
2. Overt HE or a history of overt HE
3. Renal insufficiency with creatinine greater than 1.5 mg/dL (233 μmol/L)
4. Ongoing treatment for HE, including treatment with antibiotics (possible treatments should have been stopped at least one month before)
5. Need to take long term antibiotics for any reason
6. Pregnant females, or females planning to become pregnant, or nursing
7. Patients who are unable or unwilling to provide informed consent
8. Patients who are taking benzodiazepines, narcotics, anti-depressants, or anti-psychotic medication (previous medication with these drugs should have stopped by one month or more)
9. Patients with history of shunt surgery or transjugular intrahepatic portosystemic shunt (TIPSS) for portal hypertension
10. Patients with any other organic brain disease, including dementia from any cause, mental retardation, Wilson?s disease, previous stroke, TIA, etc.
11. Severe medical problems such as congestive heart failure, pulmonary disease, neurological or psychiatric disorder, etc., that could influence quality-of-life measurement;
12. Inability to perform NP tests due to bad vision
13. Patients with gastrointestinal dysfunction (motility, prior resection/surgery, obstruction)
14. Gastrointestinal bleeding within 30 days
15. Serious infection (e.g. peritonitis) within 30 days
16. Known hepatocellular carcinoma or AFP>400
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
Method of Concealment
Modification(s)
|
Sequentially numbered, sealed, opaque envelopes |
Blinding/Masking
Modification(s)
|
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| The primary outcome is the evaluation of the beneficial effects of supplementation with VSL#3® in cirrhotic patients assessed by a reduction in MHE prevalence and improvement in cognitive functions assessed by psychometric hepatic encephalopathy score (PHES). |
16 weeks |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| Assessment of the beneficial effects of food supplementation with the probiotic preparation VSL#3® on:
? Improvement in health related quality of life (HR-QOL) (SF-36 score)
? Prevention of major complications of cirrhosis (overt encephalopathy, variceal bleeding, spontaneous bacterial peritonitis, and hepatopulmonary syndrome)
? Liver function
? Renal functions
? Improvement in hypoxia
? Blood ammonia levels, blood cytokines levels,
? Small intestinal bacterial overgrowth and orocecal transit time
? HVPG
? Hospital admissions due to cirrhosis complications
? Survival time after study medication
|
16 weeks and 20 weeks |
|
Target Sample Size
Modification(s)
|
Total Sample Size="0"
Sample Size from India="72"
Final Enrollment numbers achieved (Total)= ""
Final Enrollment numbers achieved (India)="" |
|
Phase of Trial
|
Phase 2/ Phase 3 |
Date of First Enrollment (India)
Modification(s)
|
01/08/2009 |
| Date of Study Completion (India) |
Date Missing |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Date Missing |
Estimated Duration of Trial
Modification(s)
|
Years="2"
Months="6"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Completed |
|
Publication Details
|
|
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
This is a randomized, double-blind, placebo controlled trial to study supplementation with a probiotic preparation, VSL#3® as a support pharmaceutical therapy in cirrhotic patients for the treatment of minimal hepatic encephalopathy (MHE). The study Period is for24 months from the beginning (recruitment: 18 months; VSL#3® supplementation or placebo: 16 weeks). The study population for screening will comprise 150 adult cirrhotic patients (as per hospital prevalence rates) of which 72 would be enrolled for the study: 50% of the patients with MHE will be randomised to receive VSL#3® and 50% to receive placebo. The dose which each patients will receive is one sachet of VSL#3® or placebo per day for 16 weeks. The primary outcome is the evaluation of the beneficial effects of VSL#3® supplementation in cirrhotic patients assessed by a reduction in MHE prevalence and improvement in cognitive functions assessed by psychometric hepatic encephalopathy score (PHES). The secondary outcomes are as follows: Improvement in health related quality of life (HRQOL) assessed by the SF-36 score, liver and renal functions, prevention of major complications of cirrhosis (overt hepatic encephalopathy, variceal bleeding, spontaneous bacterial peritonitis, and hepatopulmonary syndrome), blood ammonia levels, blood cytokines levels, hospital admissions due to cirrhosis complications and survival time after medication. Physical status evaluations include assessment of PHES and SF-36 scores, venous phlebotomy (for Child class, MELD score, ammonia, PCR, endotoxins, interleukin 1 and 6, tumor necrosis factor alpha), H2 breath test for orocecal transit time and small intestinal bacterial overgrowth and HVPG.
|