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

Official title

Gut Microbiota Profile Analysis and Randomized Controlled Trials (RCT) Study of the Effect of Synbiotics on Insulin and TNF-α in Metabolic Dysfunction -Associated Fatty Liver Disease (MAFLD)

Overview

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.

Detailed description

Non-alcoholic Fatty Liver Disease (NAFLD) is a common chronic liver disease estimated to affect 25% of the global population. NAFLD is defined as the presence of fat in the liver that is not associated with alcohol consumption. The researchers proposed a new term, Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), which covers a range of liver conditions associated with metabolic dysregulation, including obesity and type 2 diabetes. MAFLD is a systemic disease with complications such as obesity, which is closely related to glucose and lipid metabolism. Obesity is associated with comorbidities such as dyslipidaemia, hypertension and diabetes.

The pathogenesis mechanism of MAFLD is complex and involves several factors such as mitochondrial dysfunction, oxidative stress, and increased free fatty acids (FFA). The 'multi-hit' theory explains how lifestyle, environmental and genetic factors contribute to the development of MAFLD. The gut microbiota also plays an important role in the development of MAFLD through the gut-liver axis, where microbiota imbalance can lead to inflammation and liver damage.

Research shows the microbiota composition in MAFLD patients is different from healthy people, with an increase in Proteobacteria and Actinobacteria and a decrease in butyrate-producing bacteria. Interventions with probiotics and prebiotics (synbiotics) have been shown to reduce liver fibrosis and improve metabolic profiles. The investigators are interested in assessing the effects of synbiotics on changes in metabolic biomarkers, insulin, TNF-α, and gut microbiota in MAFLD patients.

Interventions

• Dietary supplement Treatment
  RILLUS is a synbiotic produced by Kalbe Farma
• Dietary supplement Control
  Placebo produced by Kalbe Farma

Primary outcome measures

• Complete Hematology [Time frame: 3 months]
• Metabolic Profile [Time frame: 3 months]
• Metabolic Profile [Time frame: 3 months]
• Metabolic Profile [Time frame: 3 months]
• Insulin [Time frame: 3 months]
• TNF-alpha [Time frame: 3 months]
• CRP (C-Reactive Protein) [Time frame: 3 months]

Secondary outcome measures (4)

• Alpha Diversity of Gut Microbioata [Time frame: 4 months]
• Anti-HCV [Time frame: 3 months]
• HBsAg (Hepatitis B Surface Antigen) [Time frame: 3 months]
• Beta Diversity of Gut Microbioata [Time frame: 4 months]

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Indonesia · 1 center

• RSUP Dr. Kariadi — Semarang

Publications

• 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 UNDI
• 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-asso PMID 38303507
• The Relationship between the Duration of Suffering from Diabetes and HbA1c Levels with the Degree of Liver Stiffness in Type 2 Diabetes Mellitus Patients
• 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
• 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
• 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
• 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 m PMID 32278004
• 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

Identifiers

NCT: NCT06585982 · CT-1583

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗