Silymarin in NAFLD

Study Overview
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Brief Summary
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This study evaluates the influence of Silymarin in reducing laboratory, ultrasonographic (Fibroscan) and metabolic components of NAFLD. Half of the patients will receive Silymarin (Verum) while the other half will receive placebo

Detailed Description
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In this study will participate patients who come to the regular ambulatory examinations (referred by gastroenterologists, nephrologists or family physicians in the Department of Gastroenterology and Department of Nephrology, dialysis and kidney transplantation KBC Rijeka) and have one or more components of the metabolic syndrome (hypertension, diabetes, obesity, dyslipidemia).Nonalcoholic fatty liver disease will be defined by transient elastography (FibroScan, Echosens, Paris); Controlled Attenuation Parameter (CAP) for assesment of liver steatosis and Liver Stiffness Measurements (LSM) for liver fibrosis. In all patients other causes of chronic liver disease will be excluded; chronic viral hepatitis, autoimmune diseases and other metabolic liver diseases as well as use of drugs than can cause liver steatosis and fibrosis and alcoholic liver disease. This study will include 350 patients. Taking into account the possible drop-out rate around 15% of the patients during the study period, a total of 400 patients will be randomized. Patients will be randomized into two groups. The first group will be consisted of the patients with NAFLD who will be receiving Verum therapy during the 6 month period. The second group will be consisted of the patients with NAFLD who will be receiving placebo during the 6 months period, which will be identical to the Verum preparation in its packaging and form. After the 6 months of therapy in all patients will be evaluated: liver enzymes and metabolic laboratory parameters of NAFLD (insulin resistance, lipidogram and serum glucose), as well as the TE-CAP in order to evaluate the efficiency of Silymarin for the treatment of NAFLD.

Official Title
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Silymarin® - Efficacy in Treatment of Non-alcoholic Fatty Liver Disease (NAFLD) Controlled by Laboratory and and Elastographic Parameters

Conditions
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Non-Alcoholic Fatty Liver Disease

Intervention / Treatment
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* Drug: Silymarin
* Other: Placebo Oral Capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: NAFLD patients signed informed consent possibility to follow instruction and the protocol Exclusion Criteria: chronic B or C hepatitis usage of hepatotoxic drugs in the period of 6 months before inclusion chronic kidney insufficiency (grade 4 and 5), hemodialysis any other chronic liver disease opioid dependancy any malignancy HIV seropositivity alcohol abuse pregnancy inability to follow the protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group Silymarin<br>Silymarin 2x200 mg 8 weeks (2x2 caps) Silymarin 2x100 mg 16 weeks (2x1 caps) | Drug: Silymarin<br>* Capsules contains 100 mg of silymarin<br>|
| Placebo Comparator: Group Placebo<br>2x2 placebo caps 8 weeks 2x1 placebo caps 16 weeks | Other: Placebo Oral Capsule<br>* Capsule will be identical in shape, size and color, packed in the same way like verum<br>* Other names: no other names;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change (Reduction) of parameters of liver steatosis defined by CAP (Controlled Attenuation Parameter) and liver fibrosis defined by LSM (liver stiffness measurements) during the 6 months period | Transient elastography detected by FibroScan®, Echosense, France | 0 week (Initiation) and during 24-25 week (End of the Study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in liver enzymes in period of 6 months | AST (Aspartate Aminotransferase ) ALT (alanine aminotransferase), GGT (gamma-glutamyltransferase), ALP (Alkaline Phosphatase). All outcomes have the same units of measure (UI/L) and all together represents liver function test. | 0 week (Initiation) and during 24-25 week (End of the Study) | 
| Change in insulin resistance in period of 6 months | In the assessment of the insulin resistance HOMA-IR scoring system will be used (fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5.) | 0 week (Initiation) and during 24-25 week (End of the Study) | 
| Change in lipidogram in period of 6 months | lipidogram (total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides) All outcomes have the same units of measure (umol/L) and all together represents lipid profile | 0 week (Initiation) and during 24-25 week (End of the Study) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NAFLD;, Fibroscan, Silymarin