Role of Probiotics in Treatment of Pediatric NAFLD Patients by Assessing With Fibroscan

Study Overview
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Brief Summary
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The goal of this study is to evaluate the role of probiotics in the treatment of pediatric NAFLD by evaluating for steatosis and fibrosis with a Fibroscan machine. This will be done by performing a fibroscan during each visit and comparing patients' ALT at various intervals. This is an important study as current pediatric guidelines only recommend lifestyle modifications for the treatment of NAFLD and the use of ALT and sonogram to assess improvement as standard of care. Investigators hypothesized that treatment with a probiotic will demonstrate an improvement in NAFLD as assessed by a fibroscan of liver which is good for the monitoring of steatosis and fibrosis. Additionally, analysis of fecal microbiome results may offer insight into targeted therapy in the future.

Detailed Description
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The goal/objective of this study is to evaluate the role of probiotics in the treatment of NAFLD by assessing with fibroscan in both newly diagnosed and known pediatric patients with NAFLD. This will be done by performing a fibroscan during each visit and comparing patient ALT and fecal microbiome at various intervals. The primary endpoint is to assess the effect of probiotic treatment in liver steatosis and fibrosis by assessing with fibroscan using CAP score and TE staging. The higher the CAP score (S1, S2, S3) so worse the steatosis. TE staging (F0-F4), higher the staging indicates worsening of fibrosis. Secondary endpoints include: The rate of decline of ALT over 3 month time interval and through whole study starting at initial diagnosis. The rate of decrease in hepatic steatosis and BMI This study will target pediatric patients with NAFLD. Participants will be new and previously diagnosed NAFLD patients between the ages of 5 years and 18 years. This is single center study. Investigators will enroll patients from The Division of Pediatric Gastroenterology, Liver Disease and Nutrition. Participants will be blindly randomized into one of two groups: probiotic or placebo. Investigators expect the study to run for 1 year from 09/15/2020 to 09/14/2021. Investigators will enroll patients over a 6 month period. After randomization into two separate groups (probiotic vs placebo), Investigators plan to collect data for the subsequent 6 months following enrollment.

Official Title
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Role of Probiotics in Treatment of Pediatric Nonalcoholic Fatty Liver Disease (NAFLD) Patients by Assessing With Fibroscan

Conditions
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Non-Alcoholic Fatty Liver Disease

Intervention / Treatment
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* Dietary Supplement: Culturelle (Lactobacillus rhamnosus strain GG)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: This study will target pediatric patients with NAFLD. Participants will be new and previously diagnosed NAFLD patients between the ages of 5 years and 18 years. Diagnosis must be made by elevated serum ALT (two times above the sex specific upper limit of normal) and a sonogram consistent with steatosis Exclusion Criteria: Exclusion criteria for both groups Concomitant underlying liver disease such as but not limited to autoimmune hepatitis Concomitant infectious hepatitis Medication use of steroids, methotrexate, metformin, and therapeutic dose of Vit. E Recent antibiotic use in last 4 weeks Clinically significant weight loss (at least 5% reduction in weight from baseline level [18]) on follow up NAFLD patients who were on life style modification intervention Cirrhosis (Fibroscan score ≥14.0)>

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be blindly randomized at Visit 1 into one of two groups (probiotic or placebo). Probiotic group will receive Lactobacillus rhamnosus strain GG one capsule oral daily (10 billion CFU/day) and the other group receive placebo oral capsule daily throughout the study. All participants in either group will undergo: Life style modification as per NASPGHAN NAFLD guidelines. Fibroscan assessing CAP and TE score once every 3 month until the end of study. Monitoring ALT every 3 months until end of study as per standard of care guidelines.Collection of stool sample to be sent for microbiome analysis at the time of diagnosis, 3 months and 6 months (end of the study). Secondary variables collected, Age, Gender, Race, BMI, Fibroscan probe.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic group<br>Probiotic group will receive Lactobacillus rhamnosus strain GG one capsule oral daily (10 billion CFU/day) throughout the study | Dietary Supplement: Culturelle (Lactobacillus rhamnosus strain GG)<br>* Culturelle probiotics are typically sold over the counter as dietary supplements Probiotics group will take 1 capsule of probiotics orally once daily<br>|
| Placebo Comparator: Placebo Group<br>Placebo group is to receive placebo oral capsule daily throughout the study. | Other: Placebo<br>* Placebo group will take 1 capsule of placebo orally once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The role of probiotics in the treatment of pediatric NAFLD by evaluating for steatosis with a Fibroscan machine. | The primary endpoint/outcome assesses the effect of probiotic treatment in liver steatosis by assessing with fibroscan using CAP score. | One year | 
| The role of probiotics in the treatment of pediatric NAFLD by evaluating for fibrosis with a Fibroscan machine. | The primary endpoint/outcome assesses the effect of probiotic treatment in liver fibrosis by assessing with fibroscan using TE staging. | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of decline in ALT. | The rate of decline of ALT over 3 month time interval and through whole study starting at initial diagnosis. | One year | 
| Change in fecal microbiome | Compare changes in stool microbiome | One year | 
| Decrease in BMI | The rate of change in hepatic steatosis with change in BMI | One year |