Treatment of Nonalcoholic Fatty Liver Disease With Probiotics and Prebiotics

Nonalcoholic Fatty Liver Disease Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00870012
• Other study ID #: NAFLD-GUT#2
• Status: Completed
• Phase: N/A
• First received: March 25, 2009
• Last updated: February 20, 2014
• Start date: February 2009
• Est. completion date: January 2012

Study information

• Verified date: February 2014
• Source: Chinese University of Hong Kong
• Contact: n/a
• Is FDA regulated: No
• Health authority: Hong Kong: Department of Health
• Study type: Interventional

Clinical Trial Summary

The investigators' aim is to determine whether probiotic and prebiotic treatment plus lifestyle advice is more effective in reducing hepatic fat content than lifestyle advice alone in patients with Nonalcoholic Fatty Liver Disease (NAFLD).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Age 18 to 70 years

• Fatty liver identified by imaging studies including ultrasound, computer tomography or magnetic resonance imaging

• Elevated alanine aminotransferase (ALT) according to Prati's criteria (>30 IU/l in men and >19 IU/l in women)18

• Written informed consent obtained

Exclusion Criteria:

• Positive hepatitis B surface antigen, anti-hepatitis C virus antibody, or anti-nuclear antibody titer above 1/160

• Alcohol consumption above 30 g per week in men or 20 g per week in women

• ALT above 10 times the upper limit of normal

• Liver decompensation, as evidenced by bilirubin above 50 µmol/l, platelet count below 100 × 109/l, prothrombin time above 1.3 times the upper limit of normal, albumin below 35 g/l, presence of ascites or varices

• Use of systemic corticosteroids and methotrexate in the last 6 months

• Evidence of hepatocellular carcinoma

• Terminal illness or cancer, unless in complete remission for more than 5 years

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor)

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Nonalcoholic Fatty Liver Disease

Intervention

Drug:
• Lepicol probiotic & prebiotic formula
NAFLD patients treated with Lepicol probiotic and prebiotic formula for 24 weeks.

Other:
• Simple lifestyle advice
NAFLD patients treated with lifestyle advice.

Locations

Country	Name	City	State
China	Cheng Suen Man Shook Hepatitis Center, Institute of Digestive Disease, The Chinese University of Hong Kong, Prince of Wales Hospital	Hong Kong SAR

Sponsors (1)

Lead Sponsor	Collaborator
Chinese University of Hong Kong

Country where clinical trial is conducted

China, 

References & Publications (23)

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Bäckhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, Semenkovich CF, Gordon JI. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15718-23. Epub 2004 Oct 25. — View Citation

Balas B, Belfort R, Harrison SA, Darland C, Finch J, Schenker S, Gastaldelli A, Cusi K. Pioglitazone treatment increases whole body fat but not total body water in patients with non-alcoholic steatohepatitis. J Hepatol. 2007 Oct;47(4):565-70. Epub 2007 May 24. — View Citation

Belfort R, Harrison SA, Brown K, Darland C, Finch J, Hardies J, Balas B, Gastaldelli A, Tio F, Pulcini J, Berria R, Ma JZ, Dwivedi S, Havranek R, Fincke C, DeFronzo R, Bannayan GA, Schenker S, Cusi K. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med. 2006 Nov 30;355(22):2297-307. — View Citation

Bigorgne AE, Bouchet-Delbos L, Naveau S, Dagher I, Prévot S, Durand-Gasselin I, Couderc J, Valet P, Emilie D, Perlemuter G. Obesity-induced lymphocyte hyperresponsiveness to chemokines: a new mechanism of Fatty liver inflammation in obese mice. Gastroenterology. 2008 May;134(5):1459-69. doi: 10.1053/j.gastro.2008.02.055. Epub 2008 Mar 4. — View Citation

Bugianesi E, Leone N, Vanni E, Marchesini G, Brunello F, Carucci P, Musso A, De Paolis P, Capussotti L, Salizzoni M, Rizzetto M. Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology. 2002 Jul;123(1):134-40. — View Citation

Canani RB, Cirillo P, Terrin G, Cesarano L, Spagnuolo MI, De Vincenzo A, Albano F, Passariello A, De Marco G, Manguso F, Guarino A. Probiotics for treatment of acute diarrhoea in children: randomised clinical trial of five different preparations. BMJ. 2007 Aug 18;335(7615):340. Epub 2007 Aug 9. — View Citation

Cole JR, Chai B, Farris RJ, Wang Q, Kulam SA, McGarrell DM, Garrity GM, Tiedje JM. The Ribosomal Database Project (RDP-II): sequences and tools for high-throughput rRNA analysis. Nucleic Acids Res. 2005 Jan 1;33(Database issue):D294-6. — View Citation

Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA. Diversity of the human intestinal microbial flora. Science. 2005 Jun 10;308(5728):1635-8. Epub 2005 Apr 14. — View Citation

Farrell GC, Larter CZ. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology. 2006 Feb;43(2 Suppl 1):S99-S112. Review. — View Citation

Fassio E, Alvarez E, Domínguez N, Landeira G, Longo C. Natural history of nonalcoholic steatohepatitis: a longitudinal study of repeat liver biopsies. Hepatology. 2004 Oct;40(4):820-6. — View Citation

Hickson M, D'Souza AL, Muthu N, Rogers TR, Want S, Rajkumar C, Bulpitt CJ. Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial. BMJ. 2007 Jul 14;335(7610):80. Epub 2007 Jun 29. — View Citation

Hui AY, Wong VW, Chan HL, Liew CT, Chan JL, Chan FK, Sung JJ. Histological progression of non-alcoholic fatty liver disease in Chinese patients. Aliment Pharmacol Ther. 2005 Feb 15;21(4):407-13. — View Citation

Ley RE, Bäckhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI. Obesity alters gut microbial ecology. Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):11070-5. Epub 2005 Jul 20. — View Citation

Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature. 2006 Dec 21;444(7122):1022-3. — View Citation

Lichtman SN, Sartor RB, Keku J, Schwab JH. Hepatic inflammation in rats with experimental small intestinal bacterial overgrowth. Gastroenterology. 1990 Feb;98(2):414-23. — View Citation

Lutchman G, Modi A, Kleiner DE, Promrat K, Heller T, Ghany M, Borg B, Loomba R, Liang TJ, Premkumar A, Hoofnagle JH. The effects of discontinuing pioglitazone in patients with nonalcoholic steatohepatitis. Hepatology. 2007 Aug;46(2):424-9. — View Citation

Prati D, Taioli E, Zanella A, Della Torre E, Butelli S, Del Vecchio E, Vianello L, Zanuso F, Mozzi F, Milani S, Conte D, Colombo M, Sirchia G. Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann Intern Med. 2002 Jul 2;137(1):1-10. — View Citation

Samaha FF, Iqbal N, Seshadri P, Chicano KL, Daily DA, McGrory J, Williams T, Williams M, Gracely EJ, Stern L. A low-carbohydrate as compared with a low-fat diet in severe obesity. N Engl J Med. 2003 May 22;348(21):2074-81. — View Citation

Targher G, Bertolini L, Rodella S, Tessari R, Zenari L, Lippi G, Arcaro G. Nonalcoholic fatty liver disease is independently associated with an increased incidence of cardiovascular events in type 2 diabetic patients. Diabetes Care. 2007 Aug;30(8):2119-21. Epub 2007 May 22. — View Citation

Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006 Dec 21;444(7122):1027-31. — View Citation

Villanova N, Moscatiello S, Ramilli S, Bugianesi E, Magalotti D, Vanni E, Zoli M, Marchesini G. Endothelial dysfunction and cardiovascular risk profile in nonalcoholic fatty liver disease. Hepatology. 2005 Aug;42(2):473-80. — View Citation

Wong VW, Hui AY, Tsang SW, Chan JL, Tse AM, Chan KF, So WY, Cheng AY, Ng WF, Wong GL, Sung JJ, Chan HL. Metabolic and adipokine profile of Chinese patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2006 Sep;4(9):1154-61. Epub 2006 Aug 14. — View Citation

* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary endpoint is the reduction in hepatic triglyceride content from baseline to week 24.		24 weeks	No
Secondary	The proportion of patients with normal ALT at week 24 will be determined. Normal ALT is defined according to Prati's cutoffs (=30 IU/l in men and =19 IU/l in women).		24 weeks	No
Secondary	The proportion of patients with impaired fasting glucose, diabetes, insulin resistance (estimated by the homeostasis model), hypertension, dyslipidemia and metabolic syndrome will be determined both at baseline and during each visit.		24 weeks	No
Secondary	The changes in visceral fat will be determined by magnetic resonance imaging at the same session both at baseline and month 12.		12 months	No
Secondary	The changes in liver fibrosis will be determined by transient elastography by Fibroscan both at baseline and month 12.		12 months	No
Secondary	The percentage of total sequences of individual microbes will be calculated. In particular, the proportion of Firmicutes and Bacteroidetes will be compared between the two treatment arms.		12 months	No