- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00870012
Treatment of Nonalcoholic Fatty Liver Disease With Probiotics and Prebiotics
February 20, 2014 updated by: Henry LY Chan, Chinese University of Hong Kong
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).
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
20
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Hong Kong SAR, China
- Cheng Suen Man Shook Hepatitis Center, Institute of Digestive Disease, The Chinese University of Hong Kong, Prince of Wales Hospital
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years to 68 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Lepicol probiotic & prebiotic formula+simple lifestyle advice
|
NAFLD patients treated with Lepicol probiotic and prebiotic formula for 24 weeks.
NAFLD patients treated with lifestyle advice.
|
Placebo Comparator: Simple lifestyle advice alone
|
NAFLD patients treated with lifestyle advice.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
The primary endpoint is the reduction in hepatic triglyceride content from baseline to week 24.
Time Frame: 24 weeks
|
24 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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).
Time Frame: 24 weeks
|
24 weeks
|
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.
Time Frame: 24 weeks
|
24 weeks
|
The changes in visceral fat will be determined by magnetic resonance imaging at the same session both at baseline and month 12.
Time Frame: 12 months
|
12 months
|
The changes in liver fibrosis will be determined by transient elastography by Fibroscan both at baseline and month 12.
Time Frame: 12 months
|
12 months
|
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.
Time Frame: 12 months
|
12 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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. doi: 10.1053/gast.2002.34168.
- 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. doi: 10.1056/NEJMoa060326.
- 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. doi: 10.7326/0003-4819-137-1-200207020-00006.
- Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature. 2006 Dec 21;444(7122):1022-3. doi: 10.1038/4441022a.
- 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. doi: 10.1136/bmj.39272.581736.55. Epub 2007 Aug 9.
- Backhed 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. doi: 10.1073/pnas.0407076101. Epub 2004 Oct 25.
- 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. doi: 10.1126/science.1110591. Epub 2005 Apr 14.
- 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. doi: 10.1038/nature05414.
- Ley RE, Backhed 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. doi: 10.1073/pnas.0504978102. Epub 2005 Jul 20.
- Farrell GC, Larter CZ. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology. 2006 Feb;43(2 Suppl 1):S99-S112. doi: 10.1002/hep.20973.
- Fassio E, Alvarez E, Dominguez N, Landeira G, Longo C. Natural history of nonalcoholic steatohepatitis: a longitudinal study of repeat liver biopsies. Hepatology. 2004 Oct;40(4):820-6. doi: 10.1002/hep.20410.
- 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. doi: 10.1111/j.1365-2036.2005.02334.x.
- 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. doi: 10.1002/hep.20781.
- 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. doi: 10.1016/j.cgh.2006.06.011. Epub 2006 Aug 14.
- 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. doi: 10.2337/dc07-0349. Epub 2007 May 22. No abstract available.
- 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. doi: 10.1002/hep.21661.
- 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. doi: 10.1016/j.jhep.2007.04.013. Epub 2007 May 24.
- 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. doi: 10.1056/NEJMoa022637.
- 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. doi: 10.1016/0016-5085(90)90833-m.
- Bigorgne AE, Bouchet-Delbos L, Naveau S, Dagher I, Prevot 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.
- 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. doi: 10.1136/bmj.39231.599815.55. Epub 2007 Jun 29.
- Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997 Sep 1;25(17):3389-402. doi: 10.1093/nar/25.17.3389.
- 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. doi: 10.1093/nar/gki038.
- Wong VW, Won GL, Chim AM, Chu WC, Yeung DK, Li KC, Chan HL. Treatment of nonalcoholic steatohepatitis with probiotics. A proof-of-concept study. Ann Hepatol. 2013 Mar-Apr;12(2):256-62.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
February 1, 2009
Primary Completion (Actual)
January 1, 2012
Study Completion (Actual)
January 1, 2012
Study Registration Dates
First Submitted
March 25, 2009
First Submitted That Met QC Criteria
March 25, 2009
First Posted (Estimate)
March 26, 2009
Study Record Updates
Last Update Posted (Estimate)
February 24, 2014
Last Update Submitted That Met QC Criteria
February 20, 2014
Last Verified
February 1, 2014
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- NAFLD-GUT#2
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Nonalcoholic Fatty Liver Disease
-
University of AarhusCompletedNASH - Nonalcoholic Steatohepatitis | NAFLD - Nonalcoholic Fatty Liver DiseaseDenmark
-
Columbia UniversityThorne Research Inc.WithdrawnNASH - Nonalcoholic Steatohepatitis | NAFLD - Nonalcoholic Fatty Liver Disease
-
Merck Sharp & Dohme LLCRecruitingNon-alcoholic Fatty Liver Disease | NAFLD | Nonalcoholic Fatty Liver Disease | Nonalcoholic Steatohepatitis | Fatty Liver, NonalcoholicCanada, United States, Puerto Rico, Israel, Japan, Korea, Republic of, Taiwan, Spain, Chile, France, Italy, Hungary, Switzerland, Belgium, China, Singapore, Czechia, Portugal, Austria, United Kingdom, Thailand, Hong Kong, Turkey
-
Columbia UniversityPfizerWithdrawnNASH (Nonalcoholic Steatohepatitis) | NAFLD (Nonalcoholic Fatty Liver Disease)
-
AdventHealth Translational Research InstituteCompletedNASH - Nonalcoholic Steatohepatitis; NAFLD - Nonalcoholic Fatty Liver DiseaseUnited States
-
AstraZenecaCompletedNon-alcoholic Fatty Liver Disease | NAFLD | Nonalcoholic Fatty Liver Disease | Nonalcoholic Steatohepatitis | NASH | Fatty Liver, NonalcoholicUnited States
-
Shiraz University of Medical SciencesCompletedFatty Liver | Fatty Liver, NonalcoholicIran, Islamic Republic of
-
Miriam Vos, MDImmuron Ltd.; Advanced MR Analytics ABCompletedNonalcoholic Fatty Liver Disease (NAFLD)United States
-
Assistance Publique - Hôpitaux de ParisCompletedNonalcoholic Fatty Liver Disease (NAFLD)France
-
Massachusetts General HospitalCompletedNonalcoholic Fatty Liver Disease (NAFLD)United States
Clinical Trials on Lepicol probiotic & prebiotic formula
-
Centros de Investigación de Nutrición y SaludNutribioticaCompletedFunctional ConstipationSpain
-
Assistance Publique - Hôpitaux de ParisBlédina SA, Villefranche sur Saône, FranceCompletedPreterms With Gestational Age Ranging From 30 to 35 WeeksFrance
-
AronPharma Sp. z o. o.Recruiting
-
BLIS Technologies LimitedRecruiting
-
Wageningen University and ResearchNexira; Roquette Freres; Bioiberica; Ingredion Incorporated; Naturex; Ministery of... and other collaboratorsCompleted
-
Istituto Clinico HumanitasRecruiting
-
China Medical University HospitalGlac Biotech Co., LtdCompletedProbiotics Infant Formula | Infants HealthTaiwan
-
Vanderbilt University Medical CenterNot yet recruitingHIV | Non-Alcoholic Fatty Liver Disease | Metabolic-Associated Steatotic Liver DiseaseUnited States
-
University of HelsinkiUnknownFood Hypersensitivity | Asthma | Atopic Dermatitis | Allergic Conjunctivitis | Allergic Rhinitis, SeasonalFinland