Probiotics in Pediatric Chronic Cholestasis

Study Overview
=================
Brief Summary
-----------------
double blinded RCT (probiotics vs placebo) given to pediatric patients with chronic cholestasis for 4 weeks duration. baseline characteristics (antropometry, gastrointestinal symptoms, laboratory examinations) would be compared pre vs post treatment

Detailed Description
-----------------
In mice model of cirrhosis and ascites, there is an increased intestinal permeability (leaky gut syndrome), subsequently leads to bacterial translocation. Bacterial translocation ultimately leads to bacterial overgrowth and increases associated morbidity, for instance, protracted diarrhea. This RCT aims to administer probiotics product (lacto-B) in pediatric patients with chronic cholestasis (cholestasis > 4 weeks, evidenced from laboratory examination results). method: double-blinded RCT regimen: (identical, plain silver packaging, with code 0/1 --> revealed by 3rd party upon study completion) intervention group: lacto-B 2 sachet per day for 4 weeks (28 days) each sachet of lacto-B contains: Viable Counts 1 x 107 CFU/g living bacteria in dual pH dependent release coated (Lactobacillus acidophilus, Bifidobacterium longum, Streptococcus thermophilus), Vitamin C 10 mg, Vitamin B1 0.5 mg, Vitamin B2 0.5 mg, Vitamin B6 0.5 mg, Niacin 2 mg. control group: placebo sachet (saccharum lactis 1gr) outcomes will be measured following completion of 4 weeks-course of probiotics/placebo

Official Title
-----------------
The Role of Probiotics in Chronic Cholestasis to Prevent Gastrointestinal Diseases in Pediatric Patients in Cipto Mangunkusumo Hospital

Conditions
-----------------
Cholestatic Liver Disease

Intervention / Treatment
-----------------
* Other: placebo
* Combination Product: probiotics


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: diagnosed with chronic cholestasis (>4 weeks evidence of cholestasis from laboratory evidence) patient/guardian give consent to participate Exclusion Criteria: immunocompromised consumed antibiotic within 2 weeks prior to recruitment time patient already consuming probiotic-added formula (any probiotic supplementation or formula milk with added probiotic)

Ages Eligible for Study
-----------------
Minimum Age: 29 Days
Maximum Age: 215 Months

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: probiotics<br>2 sachets per day for 4 weeks. 1 sachet of probiotics (1gram) contains: Viable Counts 1 x 107 CFU/g living bacteria in dual pH dependent release coated (Lactobacillus acidophilus, Bifidobacterium longum, Streptococcus thermophilus), Vitamin C 10 mg, Vitamin B1 0.5 mg, Vitamin B2 0.5 mg, Vitamin B6 0.5 mg, Niacin 2 mg. | Combination Product: probiotics<br>* Lactobacillus acidophilus, Bifidobacterium longum, Strepococcus thermophilus<br>|
| Placebo Comparator: placebo<br>2 sachets per day for 4 weeks. 1 sachet of placebo (1gram) contains: saccharum lactis | Other: placebo<br>* saccharum lactis<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| macroscopic fecal analysis | consistency of stool according to Bristol stool chart | 28th day of product consumption | 
| microscopic fecal erythrocyte count | fecal erythrocyte count per high power field | 28th day of product consumption | 
| microscopic fecal leukocyte count | fecal leukocyte count per high power field | 28th day of product consumption | 
| fecal calprotectin | fecal calprotectin measured using ELISA technique, reported in micrograms/gram | 28th day of product consumption | 
| gut microbiota diversity | PCR of gut microbiota diversity | 28th day of product consumption | 
| presence of intestinal bacteria overgrowth | measured using hydrogen breath test | 28th day of product consumption | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| albumin | serum albumin level measured in umol/L | 28th day of product consumption | 
| ALT | serum ALT measured in u/L | 28th day of product consumption | 
| AST | serum AST measured in u/L | 28th day of product consumption | 
| ALP | serum ALP measured in u/L | 28th day of product consumption | 
| GGT | serum GGT measured in u/L | 28th day of product consumption | 
| bilirubin level | serum total, direct and indirect bilirubin levels measured in u/L | 28th day of product consumption | 
| incidence of diarrhea | any episode of diarrhea within intervention period (>3x/day, loose bowel, or exceeds usual frequency for infants) | day 1- day 28 of product consumption | 
| antibiotic use | any antibiotic consumption as indicated by presence of infection (any organ system) | day1 - day 28 of product consumption |