Clinical trial NCT00808990: The Effect of Probiotics on Non Alcoholic Fatty Liver Disease
Official title: Probiotics and Non Alcoholic Steatohepatitis (NASH)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Liver Disease
Keywords: Non Alcoholic Fatty Liver Disease
Non Alcoholic SteatoHepatitis
Small bowel bacterial overgrowth
Probiotics
Patients with Non Alcoholic Fatty Liver Disease
Lead sponsor: Rabin Medical Center
Sponsor class: OTHER
First posted: 2008-12-16
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: SIBO in NASH patients in both treated groups (probiotics treated versus placebo treated) will be evaluated by lactulose breath test
timeFrame: Recruitment period of 6 months and 6 months of treatment after each recruitment
measure: Lactulose breath test
timeFrame: Measurement at recruitment (0) and at the end of treatment period (6 mo)
Secondary outcomes:
measure: FIBROMAX tests will assess severity of NAFLD in patients' group prior to treatment and post treatment
timeFrame: At recruitment to the study (0) and at the end of treatment (6 mo)
measure: Fibromax test for the evaluation of NAFLD severity
timeFrame: At the recruitment (0) and at the end of treatment (6 mo)
Other outcomes:
Locations:
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
Study officials:
affiliation: Rabin Medical Center
name: Hemda Weiss, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Chitturi S, Farrell GC. Etiopathogenesis of nonalcoholic steatohepatitis. Semin Liver Dis. 2001;21(1):27-41. doi: 10.1055/s-2001-12927.
citation: 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.
citation: 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.