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NCT Number: NCT06585982

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

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.

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Key information

Age range

25 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Treatment

Dietary Supplement

RILLUS is a synbiotic produced by Kalbe Farma

Control

Dietary Supplement

Placebo produced by Kalbe Farma

Primary outcomes

  1. Complete Hematology

    Time frame: 3 months

    Complete Hematology analysis before and after intervention

  2. Metabolic Profile

    Time frame: 3 months

    Analyzing fasting glucose and HbA1C before and after the intervention

  3. Metabolic Profile

    Time frame: 3 months

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

  4. Metabolic Profile

    Time frame: 3 months

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

  5. Insulin

    Time frame: 3 months

    Insulin test results were taken before and after the intervention

  6. TNF-alpha

    Time frame: 3 months

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

  7. CRP (C-Reactive Protein)

    Time frame: 3 months

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

Secondary outcomes

  1. Alpha Diversity of Gut Microbioata

    Time frame: 4 months

    Calculation of Gut Microbiota's species diversity index using Shannon Index, where the gene expresion were observed at OTUs level.

  2. Anti-HCV

    Time frame: 3 months

    Anti-HCV test is used as a screening to ensure respondents do not have hepatitis

  3. HBsAg (Hepatitis B Surface Antigen)

    Time frame: 3 months

    HBsAg test is used as a screening to ensure respondents do not have hepatitis

  4. Beta Diversity of Gut Microbioata

    Time frame: 4 months

    Calculation of Gut Microbiota's species diversity index using Bray Curtis, where the gene expresion were observed at OTUs level.

Study contacts

Contact information is provided by the study sponsor or research team.

Adiyan Pramono, PhD

CONTACT

[email protected]

+6281282037051

Hery D Purnomo, Dr

CONTACT

[email protected]

+628122803136

Sponsors and collaborators

Lead sponsor

Universitas Diponegoro

Other

Collaborators

  • Dr. Kariadi General Hospital Medical Center
  • PT Kalbe Farma Tbk

Registry information

Official study 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)

Important dates

Study start
2024
Primary completion
2025
Study completion
2025
First posted
Sep 19, 2024
Registry last updated
Nov 12, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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