Synbiotics Impact on Insulin and TNF-α in MAFLD: a Gut Microbiota Profile Analysis

NCT06585982 | Recruiting DMC

• 1 other identifier: CT-1583
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objective: To analyze the effect of synbiotic supplementation on metabolic profile, insulin and TNF-α and gut microbiota changes in patients with Metabolic dysfunction-Associated Fatty Liver Disease (MAFLD). Research question: Are there any changes in metabolic profile, Insulin and TNF-α and gut microbiota changes in MAFLD patients after synbiotic supplementation Participants will:

• Treatment group given supplementation and the control group will be given placebo at a dose of 2x1 tablet for 12 weeks.
• Patients will visit the hospital every 28 days for up to 4 months for control and follow-up supplementation.
• patients will be given a supplement consumption compliance logbook and a food record logbook used to record food consumption filled in by the patient.

Conditions

Fatty Liver Disease

Keywords

Metabolic dysfunction-associated fatty liver disease; Gut Microbiota; Metabolic profile; Synbiotic

Outcome Measures

Primary Outcomes (7)

• Complete Hematology

  Complete Hematology analysis before and after intervention

  3 months

• Metabolic Profile

  Analyzing fasting glucose and HbA1C before and after the intervention

  3 months

• Metabolic Profile

  Analyzing liver function SGOT (Serum Glutamic Oxaloacetic Transaminase) and SGPT (Serum Glutamic Pyruvic Transaminase) before and after intervention

  3 months

• Metabolic Profile

  Analyzing lipid profile (total cholesterol, triglycerides, HDL, LDL) before and after intervention

  3 months

• Insulin

  Insulin test results were taken before and after the intervention

  3 months

• TNF-alpha

  TNF-alpha test results were taken before and after the intervention

  3 months

• CRP (C-Reactive Protein)

  Analyzing C-Reactive Protein (CRP) before and after intervention

  3 months

Secondary Outcomes (4)

• Alpha Diversity of Gut Microbioata

  4 months

• Anti-HCV

  3 months

• HBsAg (Hepatitis B Surface Antigen)

  3 months

• Beta Diversity of Gut Microbioata

  4 months

Study Arms (2)

RILLUS

ACTIVE COMPARATOR

Treatment group receive RILLUS, a synbiotic that each tablet contains Viable cells 1.0 x 109 CFU containing three types of prebiotic species (Lactobacillus plantarum 8.55mg, Streptococcus thermophilus 8.55mg, and Bifidobacterium bifidum 2.55 mg) and Fructooligosaccharide (FOS) 480 mg as prebiotic.

Dietary Supplement: Treatment

Placebo

PLACEBO COMPARATOR

Control group receive what appeared to be RILLUS, but only placebo containing Fructooligosaccharide, Xylitol DC, Isomalt, Microcrystalline cellulose, Corn starch, Milk flavor powder, Hydroxypropyl methylcellulose, Vanilla flavor powder, Magnesium stearate

Dietary Supplement: Control

Interventions

Treatment DIETARY_SUPPLEMENT

RILLUS is a synbiotic produced by Kalbe Farma

RILLUS

Control DIETARY_SUPPLEMENT

Placebo produced by Kalbe Farma

Placebo

Eligibility Criteria

• Age: 25 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Adult patients aged 25-55 years
• Patients are willing to become research respondents after filling out informed consent
• Patients can and are willing to consume supplements orally within a predetermined time
• Patients are willing to record compliance with taking supplements in a diary that has been provided
• Patients diagnosed with MAFLD by FibroScan interpreted by a specialist in gastroenterology-hepatology with a CAP score ≥263 dB/m

You may not qualify if:

• Patients with hepatitis (hepatitis B, hepatitis C, and autoimmune hepatitis) and alcoholic liver disease, cirrhosis of the liver
• Patients who are pregnant, or breastfeeding or in a programme to become pregnant during participation in this study.
• Patients with a history of alcohol consumption \>40 g/day.
• Patients with a history of decompensated disease including ascites, encephalopathy, variceal haemorrhage
• Patients with Hepatocellular Carcinoma (HCC)
• Patients with a history of bowel resection or bariatric surgery Patients with chronic inflammatory bowel disease (IBD)
• Patients with a history of antibiotic use or probiotic/prebiotic/synbiotic consumption in the past 1 month
• Use of Vitamin E and omega-3 fatty acids
• Patients who were not hospitalised in the last month and therefore did not have any food restrictions related to their illness.

Sponsors & Collaborators

• Universitas Diponegoro: lead
• Dr. Kariadi General Hospital Medical Center: collaborator
• PT Kalbe Farma Tbk: collaborator

Study Sites (1)

RSUP Dr. Kariadi

Semarang, Semarang, 50244, Indonesia

RECRUITING

Related Publications (19)

• Meagratia, R. A., Cayami, F. K., Bahrudin, U., Lestari, W., Maharani, N., Faradz, S. M., & Purnomo, H. D. (2021). Adiponutrin and Adiponectin Gene Variants in Indonesian Patients with Non-Alcoholic Fatty Liver Disease: a Preliminary Study. In Journal of Biomedicine and Translational Research (Vol. 7, Issue 2, pp. 86-91). Institute of Research and Community Services Diponegoro University (LPPM UNDIP). https://doi.org/10.14710/jbtr.v7i2.11777

  BACKGROUND

• Verma N, Duseja A, Mehta M, De A, Lin H, Wong VW, Wong GL, Rajaram RB, Chan WK, Mahadeva S, Zheng MH, Liu WY, Treeprasertsuk S, Prasoppokakorn T, Kakizaki S, Seki Y, Kasama K, Charatcharoenwitthaya P, Sathirawich P, Kulkarni A, Purnomo HD, Kamani L, Lee YY, Wong MS, Tan EXX, Young DY. Machine learning improves the prediction of significant fibrosis in Asian patients with metabolic dysfunction-associated steatotic liver disease - The Gut and Obesity in Asia (GO-ASIA) Study. Aliment Pharmacol Ther. 2024 Mar;59(6):774-788. doi: 10.1111/apt.17891. Epub 2024 Feb 1.

  PMID: 38303507 BACKGROUND

• The Relationship between the Duration of Suffering from Diabetes and HbA1c Levels with the Degree of Liver Stiffness in Type 2 Diabetes Mellitus Patients

  BACKGROUND

• Byrne CD, Targher G. NAFLD: a multisystem disease. J Hepatol. 2015 Apr;62(1 Suppl):S47-64. doi: 10.1016/j.jhep.2014.12.012.

  PMID: 25920090 BACKGROUND

• Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, Harrison SA, Brunt EM, Sanyal AJ. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018 Jan;67(1):328-357. doi: 10.1002/hep.29367. Epub 2017 Sep 29. No abstract available.

  PMID: 28714183 BACKGROUND

• Boccatonda A, Andreetto L, D'Ardes D, Cocco G, Rossi I, Vicari S, Schiavone C, Cipollone F, Guagnano MT. From NAFLD to MAFLD: Definition, Pathophysiological Basis and Cardiovascular Implications. Biomedicines. 2023 Mar 13;11(3):883. doi: 10.3390/biomedicines11030883.

  PMID: 36979861 BACKGROUND

• Eslam M, Newsome PN, Sarin SK, Anstee QM, Targher G, Romero-Gomez M, Zelber-Sagi S, Wai-Sun Wong V, Dufour JF, Schattenberg JM, Kawaguchi T, Arrese M, Valenti L, Shiha G, Tiribelli C, Yki-Jarvinen H, Fan JG, Gronbaek H, Yilmaz Y, Cortez-Pinto H, Oliveira CP, Bedossa P, Adams LA, Zheng MH, Fouad Y, Chan WK, Mendez-Sanchez N, Ahn SH, Castera L, Bugianesi E, Ratziu V, George J. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement. J Hepatol. 2020 Jul;73(1):202-209. doi: 10.1016/j.jhep.2020.03.039. Epub 2020 Apr 8.

  PMID: 32278004 BACKGROUND

• Mathews SE, Kumar RB, Shukla AP. Nonalcoholic steatohepatitis, obesity, and cardiac dysfunction. Curr Opin Endocrinol Diabetes Obes. 2018 Oct;25(5):315-320. doi: 10.1097/MED.0000000000000432.

  PMID: 30074500 BACKGROUND

• Rachmatullah TF, Permatadewi CO, Hutami HT, Limantoro C, Purnomo, MD, PhD HD. Correlation between Non-Alcoholic Fatty Liver Disease (NAFLD) fibrosis score (NFS) with Left Ventricular Mass Index (LVMI) in patients with NAFLD. J Biomed Transl Res. 2021 Aug 31;7(2):79-85.

  BACKGROUND

• Purnomo HD, Kasno, Sudijanto E, Hirlan, Darmono, Daldiyono, et al. The roles of metabolic syndrome and several biomarkers in incidence and severity of non-alcoholic fatty liver disease. Hiroshima J Med Sci. 2018;67(4):138-46.

  BACKGROUND

• Buzzetti E, Pinzani M, Tsochatzis EA. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism. 2016 Aug;65(8):1038-48. doi: 10.1016/j.metabol.2015.12.012. Epub 2016 Jan 4.

  PMID: 26823198 BACKGROUND

• Tilg H, Adolph TE, Moschen AR. Multiple Parallel Hits Hypothesis in Nonalcoholic Fatty Liver Disease: Revisited After a Decade. Hepatology. 2021 Feb;73(2):833-842. doi: 10.1002/hep.31518. Epub 2021 Feb 6. No abstract available.

  PMID: 32780879 BACKGROUND

• Boursier J, Diehl AM. Nonalcoholic Fatty Liver Disease and the Gut Microbiome. Clin Liver Dis. 2016 May;20(2):263-75. doi: 10.1016/j.cld.2015.10.012. Epub 2015 Dec 24.

  PMID: 27063268 BACKGROUND

• Park E, Jeong JJ, Won SM, Sharma SP, Gebru YA, Ganesan R, Gupta H, Suk KT, Kim DJ. Gut Microbiota-Related Cellular and Molecular Mechanisms in the Progression of Nonalcoholic Fatty Liver Disease. Cells. 2021 Oct 2;10(10):2634. doi: 10.3390/cells10102634.

  PMID: 34685614 BACKGROUND

• Zhang Y, Yan S, Sheng S, Qin Q, Chen J, Li W, Li T, Gao X, Wang L, Ang L, Ding S. Comparison of gut microbiota in male MAFLD patients with varying liver stiffness. Front Cell Infect Microbiol. 2022 Aug 3;12:873048. doi: 10.3389/fcimb.2022.873048. eCollection 2022.

  PMID: 35992168 BACKGROUND

• Oh JH, Lee JH, Cho MS, Kim H, Chun J, Lee JH, Yoon Y, Kang W. Characterization of Gut Microbiome in Korean Patients with Metabolic Associated Fatty Liver Disease. Nutrients. 2021 Mar 21;13(3):1013. doi: 10.3390/nu13031013.

  PMID: 33801023 BACKGROUND

• Behrouz V, Aryaeian N, Zahedi MJ, Jazayeri S. Effects of probiotic and prebiotic supplementation on metabolic parameters, liver aminotransferases, and systemic inflammation in nonalcoholic fatty liver disease: A randomized clinical trial. J Food Sci. 2020 Oct;85(10):3611-3617. doi: 10.1111/1750-3841.15367. Epub 2020 Sep 4.

  PMID: 32885440 BACKGROUND

• Bomhof MR, Parnell JA, Ramay HR, Crotty P, Rioux KP, Probert CS, Jayakumar S, Raman M, Reimer RA. Histological improvement of non-alcoholic steatohepatitis with a prebiotic: a pilot clinical trial. Eur J Nutr. 2019 Jun;58(4):1735-1745. doi: 10.1007/s00394-018-1721-2. Epub 2018 May 19.

  PMID: 29779170 BACKGROUND

• Mofidi F, Poustchi H, Yari Z, Nourinayyer B, Merat S, Sharafkhah M, Malekzadeh R, Hekmatdoost A. Synbiotic supplementation in lean patients with non-alcoholic fatty liver disease: a pilot, randomised, double-blind, placebo-controlled, clinical trial. Br J Nutr. 2017 Mar;117(5):662-668. doi: 10.1017/S0007114517000204. Epub 2017 Mar 27.

  PMID: 28345499 BACKGROUND

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Therapeutics

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Hery D Purnomo, Dr

  Dr. Kariadi Medical Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hery D Purnomo, Dr

CONTACT

+628122803136; herydjagat@yahoo.co.id

Adiyan Pramono, PhD

CONTACT

+6281282037051; adriyanpramono@fk.undip.ac.id

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Drug coding and group assignment are done by the pharmacy, where the investigator only receives data in the form of sample coding but does not know whether the coded sample received an intervention or control.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer

Study Record Dates

• First Submitted: September 3, 2024
• First Posted: September 19, 2024
• Study Start: March 4, 2024
• Primary Completion: March 7, 2025
• Study Completion: March 7, 2025
• Last Updated: November 12, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

ID (1)