Clinical trial NCT02973295: Silymarin in NAFLD
Official title: Silymarin® - Efficacy in Treatment of Non-alcoholic Fatty Liver Disease (NAFLD) Controlled by Laboratory and and Elastographic Parameters
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Non-Alcoholic Fatty Liver Disease
Keywords: NAFLD;
Fibroscan
Silymarin
Lead sponsor: University Hospital Rijeka
Sponsor class: OTHER
Collaborators: name: University of Rijeka, Medical Faculty
name: Belupo
name: University of Rijeka, Faculty of Health studies
First posted: 2016-11-25
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 0 week (Initiation) and during 24-25 week (End of the Study)
Secondary outcomes:
measure: Change in liver enzymes in period of 6 months
timeFrame: 0 week (Initiation) and during 24-25 week (End of the Study)
measure: Change in insulin resistance in period of 6 months
timeFrame: 0 week (Initiation) and during 24-25 week (End of the Study)
measure: Change in lipidogram in period of 6 months
timeFrame: 0 week (Initiation) and during 24-25 week (End of the Study)
Other outcomes:
Locations:
city: Rijeka
country: Croatia
facility: Clinical Hospital Centre
state: Kresimirova 42
Study officials:
affiliation: Clinical Hospital Centre Rijek, Croatia
name: Goran Hauser, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Festi D, Schiumerini R, Marzi L, Di Biase AR, Mandolesi D, Montrone L, Scaioli E, Bonato G, Marchesini-Reggiani G, Colecchia A. Review article: the diagnosis of non-alcoholic fatty liver disease -- availability and accuracy of non-invasive methods. Aliment Pharmacol Ther. 2013 Feb;37(4):392-400. doi: 10.1111/apt.12186. Epub 2012 Dec 20.
citation: Mikolasevic I, Orlic L, Franjic N, Hauser G, Stimac D, Milic S. Transient elastography (FibroScan((R))) with controlled attenuation parameter in the assessment of liver steatosis and fibrosis in patients with nonalcoholic fatty liver disease - Where do we stand? World J Gastroenterol. 2016 Aug 28;22(32):7236-51. doi: 10.3748/wjg.v22.i32.7236.
citation: Mikolasevic I, Milic S, Orlic L, Stimac D, Franjic N, Targher G. Factors associated with significant liver steatosis and fibrosis as assessed by transient elastography in patients with one or more components of the metabolic syndrome. J Diabetes Complications. 2016 Sep-Oct;30(7):1347-53. doi: 10.1016/j.jdiacomp.2016.05.014. Epub 2016 May 20.
citation: Mikolasevic I, Orlic L, Hrstic I, Milic S. Metabolic syndrome and non-alcoholic fatty liver disease after liver or kidney transplantation. Hepatol Res. 2016 Aug;46(9):841-52. doi: 10.1111/hepr.12642. Epub 2016 Feb 4.