Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Dr. Kariadi General Hospital Medical Center | OTHER |
| PT Kalbe Farma Tbk | INDUSTRY |
Not provided
Not provided
Not provided
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:
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Treatment | Dietary Supplement | RILLUS is a synbiotic produced by Kalbe Farma |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Alpha Diversity of Gut Microbioata | Calculation of Gut Microbiota's species diversity index using Shannon Index, where the gene expresion were observed at OTUs level. | 4 months |
| Anti-HCV | Anti-HCV test is used as a screening to ensure respondents do not have hepatitis |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Hery D Purnomo, Dr | Contact | +628122803136 | herydjagat@yahoo.co.id | |
| Adiyan Pramono, PhD | Contact | +6281282037051 | adriyanpramono@fk.undip.ac.id |
| Name | Affiliation | Role |
|---|---|---|
| Hery D Purnomo, Dr | Dr. Kariadi Medical Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| RSUP Dr. Kariadi | Recruiting | Semarang | Semarang | 50244 | Indonesia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Background | 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 | ||
| 38303507 | 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. | |
| 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 |
Not provided
Not provided
Based on the consent from the respondent that already written in inform consent, we cannot legally give the information to anyone else
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D065626 | Non-alcoholic Fatty Liver Disease |
| ID | Term |
|---|---|
| D005234 | Fatty Liver |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D013812 | Therapeutics |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
| Control |
| Dietary Supplement |
Placebo produced by Kalbe Farma |
|
| 3 months |
| HBsAg (Hepatitis B Surface Antigen) | HBsAg test is used as a screening to ensure respondents do not have hepatitis | 3 months |
| Beta Diversity of Gut Microbioata | Calculation of Gut Microbiota's species diversity index using Bray Curtis, where the gene expresion were observed at OTUs level. | 4 months |
| 25920090 | 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. |
| 28714183 | 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. |
| 36979861 | 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. |
| 32278004 | 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. |
| 30074500 | 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. |
| 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. |
| 26823198 | 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. |
| 32780879 | 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. |
| 27063268 | 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. |
| 34685614 | 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. |
| 35992168 | 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. |
| 33801023 | 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. |
| 32885440 | 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. |
| 29779170 | 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. |
| 28345499 | 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. |