The Effect of Probiotics on Non Alcoholic Fatty Liver Disease

Probiotics and Non Alcoholic Steatohepatitis (NASH)

Nonalcoholic Fatty Liver Disease (NAFLD) has been suggested to be the most common cause of chronic liver disease in the general population in the Western World. In advanced stages of NAFLD, steatohepatitis (NASH) develops characterized by: steatosis, inflammation, and fibrosis progressing to cirrhosis in some patients. The knowledge of the role of small intestinal bacterial overgrowth (SIBO) in the pathogenesis of NASH has led to the proposal of probiotics as a therapeutic strategy for this disorder.

Study Overview

• Status: Terminated
• Conditions: Liver Disease
• Intervention / Treatment: Dietary supplement: BioFemale

Detailed Description

Probiotics may interfere with the development of NASH by several mechanisms. Data from an uncontrolled clinical trial in NASH patients show promising results, with improvement of liver enzymes in treated patients.

RESEARCH GOALS:

A. To assess the degree of SIBO in NAFLD patients vs. healthy controls. B. To evaluate the effect of probiotics vs. placebo on SIBO in NAFLD patients. C. To evaluate the effect of probiotics vs. placebo on disease severity (inflammation, steatosis, and fibrosis) in NAFLD patients.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 1

Contacts and Locations

Study Locations

• Israel
  • Petach Tikva, Israel, 49100
    • Rabin Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Controls- healthy volunteers, male and female, above 18 years.
• NAFLD group - patients with histological proven NAFLD, male and female, above 18 years.

Exclusion Criteria:

• Controls

  • those who will be found to have fatty liver in abdominal ultra sound
  • any participant who will take antibiotics for any indication for more than 1 week during the study period or before recruitment to the study
  • any participant who had lost more than 10% of baseline body weight during the study period.

• NAFLD group

  • those who will be found to have any concomitant liver disease (i.e., HBV/HCV/HIV/EBV/CMV infection
  • autoimmune hepatitis
  • metabolic liver disease: Wilson's disease, cholestatic liver disease: PBC/PSC, etc.)
  • any participant who will take antibiotics for any indication for more than 1 week during the study period or before recruitment to the study
  • any participant who had lost more than 10% of baseline body weight during the study period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OSA and NAFLD patients using CPAP; OSA and NAFLD patients using CPAP being followed for 6 months.	Dietary supplement: BioFemale; BioFemale 6 months.
No Intervention: control; OSA and NAFLD patients not using CPAP being followed for 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
SIBO in NASH patients in both treated groups (probiotics treated versus placebo treated) will be evaluated by lactulose breath test	Recruitment period of 6 months and 6 months of treatment after each recruitment
Lactulose breath test	Measurement at recruitment (0) and at the end of treatment period (6 mo)

Secondary Outcome Measures

Outcome Measure	Time Frame
FIBROMAX tests will assess severity of NAFLD in patients' group prior to treatment and post treatment	At recruitment to the study (0) and at the end of treatment (6 mo)
Fibromax test for the evaluation of NAFLD severity	At the recruitment (0) and at the end of treatment (6 mo)

Collaborators and Investigators

• Sponsor: Rabin Medical Center
• Investigators: Principal Investigator: Hemda Weiss, M.D., Rabin Medical Center

Publications and helpful links

General Publications

• Khoshini R, Dai SC, Lezcano S, Pimentel M. A systematic review of diagnostic tests for small intestinal bacterial overgrowth. Dig Dis Sci. 2008 Jun;53(6):1443-54. doi: 10.1007/s10620-007-0065-1.
• Yang SQ, Lin HZ, Lane MD, Clemens M, Diehl AM. Obesity increases sensitivity to endotoxin liver injury: implications for the pathogenesis of steatohepatitis. Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2557-62. doi: 10.1073/pnas.94.6.2557.
• Li Z, Yang S, Lin H, Huang J, Watkins PA, Moser AB, Desimone C, Song XY, Diehl AM. Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease. Hepatology. 2003 Feb;37(2):343-50. doi: 10.1053/jhep.2003.50048.
• Loguercio C, De Simone T, Federico A, Terracciano F, Tuccillo C, Di Chicco M, Carteni M. Gut-liver axis: a new point of attack to treat chronic liver damage? Am J Gastroenterol. 2002 Aug;97(8):2144-6. doi: 10.1111/j.1572-0241.2002.05942.x. No abstract available.
• Nair S, Cope K, Risby TH, Diehl AM. Obesity and female gender increase breath ethanol concentration: potential implications for the pathogenesis of nonalcoholic steatohepatitis. Am J Gastroenterol. 2001 Apr;96(4):1200-4. doi: 10.1111/j.1572-0241.2001.03702.x. Erratum In: Am J Gastroenterol 2001 Sep;96(9):2809. Terence RH [corrected to Risby TH].
• Chitturi S, Farrell GC. Etiopathogenesis of nonalcoholic steatohepatitis. Semin Liver Dis. 2001;21(1):27-41. doi: 10.1055/s-2001-12927.
• Wigg AJ, Roberts-Thomson IC, Dymock RB, McCarthy PJ, Grose RH, Cummins AG. The role of small intestinal bacterial overgrowth, intestinal permeability, endotoxaemia, and tumour necrosis factor alpha in the pathogenesis of non-alcoholic steatohepatitis. Gut. 2001 Feb;48(2):206-11. doi: 10.1136/gut.48.2.206.
• Solga SF, Buckley G, Clark JM, Horska A, Diehl AM. The effect of a probiotic on hepatic steatosis. J Clin Gastroenterol. 2008 Nov-Dec;42(10):1117-9. doi: 10.1097/MCG.0b013e31816d920c. No abstract available.

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: December 15, 2008
• First Submitted That Met QC Criteria: December 15, 2008
• First Posted (Estimate): December 16, 2008

Study Record Updates

• Last Update Posted (Estimate): April 8, 2016
• Last Update Submitted That Met QC Criteria: April 7, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Probiotics; Non Alcoholic Fatty Liver Disease; Small bowel bacterial overgrowth; Non Alcoholic SteatoHepatitis; Patients with Non Alcoholic Fatty Liver Disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: RMC085077CTIL; RMC local ID 5077