Probiotic Supplement Versus Placebo for the Treatment of Patients With Non-alcoholic Fatty Liver Disease

NCT06491342 | Completed DMC

• 1 other identifier: PMK GI 001
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 2

Brief Summary

Probiotic supplement versus placebo for the treatment of patients with non-alcoholic fatty liver disease: a randomized, double-blind, placebo-controlled trial

Conditions

Fatty Liver, Nonalcoholic

Keywords

Probiotic

Outcome Measures

Primary Outcomes (3)

• Liver steatosis by fibroscan

  Shear wave velocity with controlled attenuation parameter (CAP) unit in decibels per meter (dB/m)

  12 weeks

• Liver steatosis by MRI

  Hepatic steatosis with MRI-PDFF (the percent ratio of the density of mobile protons from triglycerides and the total density of protons from mobile triglycerides and mobile water). Outcome Measures was report as percent

  12 weeks

• Liver stiffness by fibroscan

  Fibroscan- transient elastography in kilopascals (kPa)

  12 weeks

Secondary Outcomes (10)

• Liver inflammation

  12 weeks

• Metabolic profile

  12 weeks

• Metabolic profile

  12 weeks

• Metabolic profile: HOMA IR

  12 weeks

• Metabolic profile: serum lipid profiles

  12 weeks

Other Outcomes (1)

• Fecal SCFA

  12 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Maltodextrin in bovine gelatin capsule look same as probiotic (250 mg/capsule ) 2 capsule twice daily after breakfast and dinner

Dietary Supplement: Placebo

probiotic

ACTIVE COMPARATOR

Lactobacillus Zeae and Lactobacillus reuteri probiotic mixed with Maltodextrin in ratio 15:85 in bovine gelatin capsule (250 mg/capsule ) 2 capsule twice daily after breakfast and dinner (1,000 mg =1x109 CFU/g)

Dietary Supplement: Probiotic

Interventions

Probiotic DIETARY_SUPPLEMENT

Probiotic-Lactobacillus Zeae and Lactobacillus reuteri

probiotic

Placebo DIETARY_SUPPLEMENT

placebo

Placebo

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Fatty liver by imaging then fibroScan with CAP ≥ 248 dB m Liver biopsy compatible with NASH/NAFLD

You may not qualify if:

• Supplement with probiotic/prebiotic within 2 weeks
• Previous antibiotic/antifungus within 1 month
• History of significant alcohol consumption for a period of more than three consecutive months within 1 year before screening. Significant alcohol consumption is defined as equal to or greater than approximately two alcoholic drinks per day for males and approximately 1.5 alcoholic drinks per day for females
• Regular use of drugs historically associated with NAFLD, which include, but are not limited, to the following: amiodarone, methotrexate, systemic glucocorticoids at greater than 5 mg/d
• Chronic liver diseases from other cause such as viral hepatitis, autoimmune hepatitis
• Hepatic decompensation or impairment defined as presence of any of the following:
• History of esophageal varices, ascites or hepatic encephalopathy.
• Serum albumin \<3.5 g dl-1, except as explained by nonhepatic causes.
• INR \> 1.4
• Use of GLP-1 agonist therapy (for example, exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, semaglutide and albiglutide), vitamin E and pioglitazone
• Active autoimmune disease, including actively treated lupus, rheumatoid arthritis, inflammatory bowel disease
• Active malignancy on treatment
• New York Heart Association Class III or IV heart failure or known left ventricular ejection fraction \<30%
• Known immunocompromised status, HIV or who have recurrent or chronic systemic bacterial, fungal, viral or protozoal infections
• Respiratory compromised

Sponsors & Collaborators

• Phramongkutklao College of Medicine and Hospital: lead
• Chiang Mai University: collaborator
• Thailand Institute of scientific and technological research: collaborator

Study Sites (2)

Division of gastroenterology and hepatology

Ratchathewi, Bangkok, 10400, Thailand

Location

Chiangmai university

Chiang Mai, 50200, Thailand

Location

Related Publications (31)

• Sanyal AJ, Brunt EM, Kleiner DE, Kowdley KV, Chalasani N, Lavine JE, Ratziu V, McCullough A. Endpoints and clinical trial design for nonalcoholic steatohepatitis. Hepatology. 2011 Jul;54(1):344-53. doi: 10.1002/hep.24376.

  PMID: 21520200 BACKGROUND

• Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016 Jul;64(1):73-84. doi: 10.1002/hep.28431. Epub 2016 Feb 22.

  PMID: 26707365 BACKGROUND

• Chang Y, Jung HS, Cho J, Zhang Y, Yun KE, Lazo M, Pastor-Barriuso R, Ahn J, Kim CW, Rampal S, Cainzos-Achirica M, Zhao D, Chung EC, Shin H, Guallar E, Ryu S. Metabolically Healthy Obesity and the Development of Nonalcoholic Fatty Liver Disease. Am J Gastroenterol. 2016 Aug;111(8):1133-40. doi: 10.1038/ajg.2016.178. Epub 2016 May 17.

  PMID: 27185080 BACKGROUND

• Schnabl B, Brenner DA. Interactions between the intestinal microbiome and liver diseases. Gastroenterology. 2014 May;146(6):1513-24. doi: 10.1053/j.gastro.2014.01.020. Epub 2014 Jan 15.

  PMID: 24440671 BACKGROUND

• Trinchieri G, Sher A. Cooperation of Toll-like receptor signals in innate immune defence. Nat Rev Immunol. 2007 Mar;7(3):179-90. doi: 10.1038/nri2038.

  PMID: 17318230 BACKGROUND

• Imajo K, Fujita K, Yoneda M, Nozaki Y, Ogawa Y, Shinohara Y, Kato S, Mawatari H, Shibata W, Kitani H, Ikejima K, Kirikoshi H, Nakajima N, Saito S, Maeyama S, Watanabe S, Wada K, Nakajima A. Hyperresponsivity to low-dose endotoxin during progression to nonalcoholic steatohepatitis is regulated by leptin-mediated signaling. Cell Metab. 2012 Jul 3;16(1):44-54. doi: 10.1016/j.cmet.2012.05.012.

  PMID: 22768838 BACKGROUND

• Wang S, Charbonnier LM, Noval Rivas M, Georgiev P, Li N, Gerber G, Bry L, Chatila TA. MyD88 Adaptor-Dependent Microbial Sensing by Regulatory T Cells Promotes Mucosal Tolerance and Enforces Commensalism. Immunity. 2015 Aug 18;43(2):289-303. doi: 10.1016/j.immuni.2015.06.014. Epub 2015 Jul 28.

  PMID: 26231118 BACKGROUND

• Cani PD, Possemiers S, Van de Wiele T, Guiot Y, Everard A, Rottier O, Geurts L, Naslain D, Neyrinck A, Lambert DM, Muccioli GG, Delzenne NM. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut. 2009 Aug;58(8):1091-103. doi: 10.1136/gut.2008.165886. Epub 2009 Feb 24.

  PMID: 19240062 BACKGROUND

• Zhu L, Baker SS, Gill C, Liu W, Alkhouri R, Baker RD, Gill SR. Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: a connection between endogenous alcohol and NASH. Hepatology. 2013 Feb;57(2):601-9. doi: 10.1002/hep.26093. Epub 2013 Jan 8.

  PMID: 23055155 BACKGROUND

• Bron PA, Kleerebezem M, Brummer RJ, Cani PD, Mercenier A, MacDonald TT, Garcia-Rodenas CL, Wells JM. Can probiotics modulate human disease by impacting intestinal barrier function? Br J Nutr. 2017 Jan;117(1):93-107. doi: 10.1017/S0007114516004037.

  PMID: 28102115 BACKGROUND

• Alisi A, Bedogni G, Baviera G, Giorgio V, Porro E, Paris C, Giammaria P, Reali L, Anania F, Nobili V. Randomised clinical trial: The beneficial effects of VSL#3 in obese children with non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2014 Jun;39(11):1276-85. doi: 10.1111/apt.12758. Epub 2014 Apr 16.

  PMID: 24738701 BACKGROUND

• Abhari K, Saadati S, Yari Z, Hosseini H, Hedayati M, Abhari S, Alavian SM, Hekmatdoost A. The effects of Bacillus coagulans supplementation in patients with non-alcoholic fatty liver disease: A randomized, placebo-controlled, clinical trial. Clin Nutr ESPEN. 2020 Oct;39:53-60. doi: 10.1016/j.clnesp.2020.06.020. Epub 2020 Jul 24.

  PMID: 32859329 BACKGROUND

• Ferolla SM, Couto CA, Costa-Silva L, Armiliato GN, Pereira CA, Martins FS, Ferrari Mde L, Vilela EG, Torres HO, Cunha AS, Ferrari TC. Beneficial Effect of Synbiotic Supplementation on Hepatic Steatosis and Anthropometric Parameters, But Not on Gut Permeability in a Population with Nonalcoholic Steatohepatitis. Nutrients. 2016 Jun 28;8(7):397. doi: 10.3390/nu8070397.

  PMID: 27367724 BACKGROUND

• Zhou D, Fan JG. Microbial metabolites in non-alcoholic fatty liver disease. World J Gastroenterol. 2019 May 7;25(17):2019-2028. doi: 10.3748/wjg.v25.i17.2019.

  PMID: 31114130 BACKGROUND

• Rau M, Rehman A, Dittrich M, Groen AK, Hermanns HM, Seyfried F, Beyersdorf N, Dandekar T, Rosenstiel P, Geier A. Fecal SCFAs and SCFA-producing bacteria in gut microbiome of human NAFLD as a putative link to systemic T-cell activation and advanced disease. United European Gastroenterol J. 2018 Dec;6(10):1496-1507. doi: 10.1177/2050640618804444. Epub 2018 Sep 30.

  PMID: 30574320 BACKGROUND

• Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, Spertus JA, Costa F; American Heart Association; National Heart, Lung, and Blood Institute. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005 Oct 25;112(17):2735-52. doi: 10.1161/CIRCULATIONAHA.105.169404. Epub 2005 Sep 12. No abstract available.

  PMID: 16157765 BACKGROUND

• Carr RM, Oranu A, Khungar V. Nonalcoholic Fatty Liver Disease: Pathophysiology and Management. Gastroenterol Clin North Am. 2016 Dec;45(4):639-652. doi: 10.1016/j.gtc.2016.07.003. Epub 2016 Oct 13.

  PMID: 27837778 BACKGROUND

• Castera L, Friedrich-Rust M, Loomba R. Noninvasive Assessment of Liver Disease in Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology. 2019 Apr;156(5):1264-1281.e4. doi: 10.1053/j.gastro.2018.12.036. Epub 2019 Jan 18.

  PMID: 30660725 BACKGROUND

• Sasso M, Beaugrand M, de Ledinghen V, Douvin C, Marcellin P, Poupon R, Sandrin L, Miette V. Controlled attenuation parameter (CAP): a novel VCTE guided ultrasonic attenuation measurement for the evaluation of hepatic steatosis: preliminary study and validation in a cohort of patients with chronic liver disease from various causes. Ultrasound Med Biol. 2010 Nov;36(11):1825-35. doi: 10.1016/j.ultrasmedbio.2010.07.005. Epub 2010 Sep 27.

  PMID: 20870345 BACKGROUND

• Dietrich CF, Bamber J, Berzigotti A, Bota S, Cantisani V, Castera L, Cosgrove D, Ferraioli G, Friedrich-Rust M, Gilja OH, Goertz RS, Karlas T, de Knegt R, de Ledinghen V, Piscaglia F, Procopet B, Saftoiu A, Sidhu PS, Sporea I, Thiele M. EFSUMB Guidelines and Recommendations on the Clinical Use of Liver Ultrasound Elastography, Update 2017 (Long Version). Ultraschall Med. 2017 Aug;38(4):e16-e47. doi: 10.1055/s-0043-103952. Epub 2017 Apr 13.

  PMID: 28407655 BACKGROUND

• Shen QL, Chen YJ, Wang ZM, Zhang TC, Pang WB, Shu J, Peng CH. Assessment of liver fibrosis by Fibroscan as compared to liver biopsy in biliary atresia. World J Gastroenterol. 2015 Jun 14;21(22):6931-6. doi: 10.3748/wjg.v21.i22.6931.

  PMID: 26078570 BACKGROUND

• Noureddin M, Lam J, Peterson MR, Middleton M, Hamilton G, Le TA, Bettencourt R, Changchien C, Brenner DA, Sirlin C, Loomba R. Utility of magnetic resonance imaging versus histology for quantifying changes in liver fat in nonalcoholic fatty liver disease trials. Hepatology. 2013 Dec;58(6):1930-40. doi: 10.1002/hep.26455. Epub 2013 Oct 17.

  PMID: 23696515 BACKGROUND

• Middleton MS, Heba ER, Hooker CA, Bashir MR, Fowler KJ, Sandrasegaran K, Brunt EM, Kleiner DE, Doo E, Van Natta ML, Lavine JE, Neuschwander-Tetri BA, Sanyal A, Loomba R, Sirlin CB; NASH Clinical Research Network. Agreement Between Magnetic Resonance Imaging Proton Density Fat Fraction Measurements and Pathologist-Assigned Steatosis Grades of Liver Biopsies From Adults With Nonalcoholic Steatohepatitis. Gastroenterology. 2017 Sep;153(3):753-761. doi: 10.1053/j.gastro.2017.06.005. Epub 2017 Jun 15.

  PMID: 28624576 BACKGROUND

• Ahn SB, Jun DW, Kang BK, Lim JH, Lim S, Chung MJ. Randomized, Double-blind, Placebo-controlled Study of a Multispecies Probiotic Mixture in Nonalcoholic Fatty Liver Disease. Sci Rep. 2019 Apr 5;9(1):5688. doi: 10.1038/s41598-019-42059-3.

  PMID: 30952918 BACKGROUND

• Doron S, Snydman DR. Risk and safety of probiotics. Clin Infect Dis. 2015 May 15;60 Suppl 2(Suppl 2):S129-34. doi: 10.1093/cid/civ085.

  PMID: 25922398 BACKGROUND

• Snydman DR. The safety of probiotics. Clin Infect Dis. 2008 Feb 1;46 Suppl 2:S104-11; discussion S144-51. doi: 10.1086/523331.

  PMID: 18181712 BACKGROUND

• Salminen MK, Rautelin H, Tynkkynen S, Poussa T, Saxelin M, Valtonen V, Jarvinen A. Lactobacillus bacteremia, clinical significance, and patient outcome, with special focus on probiotic L. rhamnosus GG. Clin Infect Dis. 2004 Jan 1;38(1):62-9. doi: 10.1086/380455. Epub 2003 Dec 4.

  PMID: 14679449 BACKGROUND

• Sullivan A, Nord CE. Probiotic lactobacilli and bacteraemia in Stockholm. Scand J Infect Dis. 2006;38(5):327-31. doi: 10.1080/00365540500449826.

  PMID: 16709533 BACKGROUND

• Zielinska D, Sionek B, Kołozyn-Krajewska D. Safety of Probiotics. Diet, Microbiome and Health. 2018;:131-161

  BACKGROUND

• Chambers ES, Viardot A, Psichas A, Morrison DJ, Murphy KG, Zac-Varghese SE, MacDougall K, Preston T, Tedford C, Finlayson GS, Blundell JE, Bell JD, Thomas EL, Mt-Isa S, Ashby D, Gibson GR, Kolida S, Dhillo WS, Bloom SR, Morley W, Clegg S, Frost G. Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults. Gut. 2015 Nov;64(11):1744-54. doi: 10.1136/gutjnl-2014-307913. Epub 2014 Dec 10.

  PMID: 25500202 BACKGROUND

• Zhou D, Pan Q, Liu XL, Yang RX, Chen YW, Liu C, Fan JG. Clostridium butyricum B1 alleviates high-fat diet-induced steatohepatitis in mice via enterohepatic immunoregulation. J Gastroenterol Hepatol. 2017 Sep;32(9):1640-1648. doi: 10.1111/jgh.13742.

  PMID: 28109017 BACKGROUND

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Probiotics

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Natchaporn Noppacroh

  phramongkutklao

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: probiotic vs placebo

Study Record Dates

• First Submitted: June 16, 2024
• First Posted: July 9, 2024
• Study Start: July 25, 2024
• Primary Completion: April 22, 2025
• Study Completion: May 28, 2025
• Last Updated: July 25, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

TH (2)