Efficacy of Silymarin in Patients With Non-alcoholic Fatty Liver Disease - The SILIVER Trial

Efficacy of Silymarin in Patients With Non-alcoholic Fatty Liver Disease - The SILIVER Trial: Randomized Clinical Trial

Non-Alcoholic Fatty Liver Disease (NAFLD) is one of the most prevalent chronic liver diseases in Brazil and its treatment is still limited. Thus, this project aims to conduct a double-blind, controlled, randomized clinical trial to evaluate the effect of silymarin on laboratory markers and clinical evolution of adult patients with NAFLD treated at Edgard Santos Hospital, as well as identify the dietary pattern of these individuals.

Study Overview

• Status: Recruiting
• Conditions: Non-Alcoholic Fatty Liver Disease
• Intervention / Treatment: Dietary supplement: Silymarin

Detailed Description

Non-Alcoholic Fatty Liver Disease (NAFLD) is one of the most prevalent chronic liver diseases in Brazil. It has a significantly increasing incidence today and is considered an important global health problem. It affects approximately 20 to 30% of the adult population and increases according to the severity of the risk factors. The diagnosis of this disease usually occurs in 10 to 20% of the non-obese individuals, 50% in the overweight and 80 to 90% in the obese, being twice as present in individuals with Metabolic Syndrome. Pharmacological treatment options for NAFLD are still limited and Silybum marianum, one of the most sought-after herbal remedies in patients with liver disease, is commonly used by patients because of the claim of the hepatoprotective effect of silymarin. Studies have demonstrated the therapeutic potential of silymarin in patients with NAFLD, but clinical trials with more judicious methodological designs is still needed to prove these effects. Thus, this project aims to evaluate the efficacy of silymarin in adult patients with NAFLD seen at the Clinic of Nutrition and Hepatology of Edgard Santos Hospital. A randomized, double-blind, controlled clinical trial lasting 12 weeks will be performed.

• Study Type: Interventional
• Enrollment (Anticipated): 132
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Camila Avelar; Phone Number: +55 +55 (71)991540434; Email: contato@camilaavelar.com.br

Study Locations

• Brazil
  • Bahia
    • Salvador, Bahia, Brazil, 40.110.060
      • Recruiting
      • Camila Ribeiro de Avelar
      • Contact: Camila Avelar; Phone Number: +55(71)991540434; Email: contato@camilaavelar.com.br

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults between 20 and 60 years of age, both men and women,
• Clinical diagnosis of NAFLD, confirmed by imaging exams,

Exclusion Criteria:

• Women in the menacing period, with the exception of those who have performed definitive sterilization, such as hysterectomy or tubal ligation.
• Patients with established prior diagnosis of chronic noncommunicable disease (congestive heart failure, decompensated or severe lung disease, neoplasms, renal disease, advanced liver disease - Child Pugh C classification)
• Patients with schistosomiasis;
• Hemochromatosis
• Wilson's disease
• Viral or autoimmune hepatitis
• HIV virus carriers
• Woman who is breastfeeding
• Users of illicit drugs
• Patients with an intake of more than 20 g / day of alcohol and / or past alcoholism with abstention less than 6 months;
• Patients with ingestion of medications such as steroids, estrogens, amiodarone, warfarin, anti-convulsants, antipsychotics, tamoxifen or other chemotherapeutic agents in the last 6 months
• Patients with clinically manifest infections or inflammation, surgery, trauma or hospitalization in the last 30 days
• Chronic non-hepatic degenerative diseases (sclerosis, Parkinson's disease or Alzheimer's disease)
• Patients who do not participate in all stages of the research.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Silymarin; Patients will receive 2 capsules containing a total of 700mg of silymarin, 8mg of vitamin E and 50mg of phosphatidylcholine, in addition to the excipient, which should be ingested daily for 12 weeks.	Dietary supplement: Silymarin; It is a randomized, double-blind, controlled clinical trial to be performed at outpatient level. The intervention will last 12 weeks and the invited participants will be patients attended at the outpatient clinic of the Edgard Santos Hospital, which will be randomized into two groups: control and intervention. Data on laboratory and clinical markers, imaging, nutritional and dietary assessment will be collected at the beginning and end of the trial for comparison purposes.
Placebo Comparator: Placebo; Patients will also receive similarly 2 capsules per day, but without the bioactive principle tested (silymarin). Therefore, the capsules in the control group will contain only 700 mg of maltodextrin, a neutral food component derived from starch, in addition to the excipient and the same amount of vitamin E and phosphatidylcholine to balance the two groups.	Dietary supplement: Silymarin; It is a randomized, double-blind, controlled clinical trial to be performed at outpatient level. The intervention will last 12 weeks and the invited participants will be patients attended at the outpatient clinic of the Edgard Santos Hospital, which will be randomized into two groups: control and intervention. Data on laboratory and clinical markers, imaging, nutritional and dietary assessment will be collected at the beginning and end of the trial for comparison purposes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absence or change in NAFLD degree	Absence or change in NAFLD degree, assessed by the value of the difference in the attenuation coefficient between liver and spleen obtained by computed tomography of the upper abdomen performed at the beginning and at the end of the study.	They will be dosed at baseline and after 12 weeks of intervention.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lipid profile	Total cholesterol (mg/dL), LDL-cholesterol (mg/dL), HDL-cholesterol (mg/dL), VLDL-cholesterol (mg/dL) and triglycerides (mg/dL) will be measured before and after the intervention.	They will be dosed at baseline and after 12 weeks of intervention.
Fasting blood glucose	Fasting blood glucose (mg/dL) will be measured before and after the intervention.	They will be dosed at baseline and after 12 weeks of intervention.
Glycated haemoglobin	Hb A1c (%) will be measured before and after the intervention.	They will be dosed at baseline and after 12 weeks of intervention.
Insulin	Insulin (µU/mL) will be measured before and after the intervention.	They will be dosed at baseline and after 12 weeks of intervention.
Serum Iron	Serum iron (mcg/dL) will be measured before and after intervention.	They will be dosed at baseline and after 12 weeks of intervention.
Transferrin saturation	Transferrin saturation (%) will be measured before and after intervention.	They will be dosed at baseline and after 12 weeks of intervention.
Serum ferritin	Serum ferritin will be evaluated in µg/L before and after intervention.	They will be dosed at baseline and after 12 weeks of intervention.
Hepatic transaminases	Alanine aminotransferase (ALT) and Aspartate Aminotransferase (AST) will be evaluated in U/L before and after intervention.	They will be dosed at baseline and after 12 weeks of intervention.
gamma glutamyl transferase	Gamma glutamyl transferase will be evaluated in U/L before and after intervention.	They will be dosed at baseline and after 12 weeks of intervention.

Collaborators and Investigators

• Sponsor: Camila Ribeiro de Avelar

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2019
• Primary Completion (Anticipated): August 31, 2022
• Study Completion (Anticipated): August 31, 2022

Study Registration Dates

• First Submitted: October 28, 2018
• First Submitted That Met QC Criteria: November 19, 2018
• First Posted (Actual): November 21, 2018

Study Record Updates

• Last Update Posted (Actual): August 2, 2022
• Last Update Submitted That Met QC Criteria: August 1, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Non-Alcoholic Fatty Liver Disease; sylimarin
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Antioxidants; Silymarin
• Other Study ID Numbers: 2.635.954

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No