Clinical trial NCT06585982: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Fatty Liver Disease
Keywords: Metabolic dysfunction-associated fatty liver disease
Gut Microbiota
Metabolic profile
Synbiotic
Lead sponsor: Universitas Diponegoro
Sponsor class: OTHER
Collaborators: name: Dr. Kariadi General Hospital Medical Center
name: PT Kalbe Farma Tbk
First posted: 2024-09-19
Enrollment: 50
Sex: ALL
Minimum age (years): 25
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

Primary outcomes:
measure: Complete Hematology
timeFrame: 3 months
measure: Metabolic Profile
timeFrame: 3 months
measure: Metabolic Profile
timeFrame: 3 months
measure: Metabolic Profile
timeFrame: 3 months
measure: Insulin
timeFrame: 3 months
measure: TNF-alpha
timeFrame: 3 months
measure: CRP (C-Reactive Protein)
timeFrame: 3 months
Secondary outcomes:
measure: Alpha Diversity of Gut Microbioata
timeFrame: 4 months
measure: Anti-HCV
timeFrame: 3 months
measure: HBsAg (Hepatitis B Surface Antigen)
timeFrame: 3 months
measure: Beta Diversity of Gut Microbioata
timeFrame: 4 months
Other outcomes:
Locations:
city: Semarang
country: Indonesia
facility: RSUP Dr. Kariadi
Study officials:
affiliation: Dr. Kariadi Medical Hospital
name: Hery D Purnomo, Dr
role: PRINCIPAL_INVESTIGATOR
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