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

Sponsor

Camila Ribeiro de Avelar (Other)

Overall Status

Recruiting

CT.gov ID

NCT03749070

Collaborator

(none)

132

Enrollment

Location

Arms

42.5

Anticipated Duration (Months)

3.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Non-Alcoholic Fatty Liver Disease	Dietary Supplement: Silymarin	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

132 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Clinical trial, randomized, double-blind and controlledClinical trial, randomized, double-blind and controlled

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Double-blind

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 15, 2019

Anticipated Primary Completion Date :

Aug 31, 2022

Anticipated Study Completion Date :

Aug 31, 2022

Arms and Interventions

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.

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

Outcome Measures

Primary Outcome Measures

Absence or change in NAFLD degree [They will be dosed at baseline and after 12 weeks of intervention.]
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.

Secondary Outcome Measures

Lipid profile [They will be dosed at baseline and after 12 weeks of intervention.]
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.
Fasting blood glucose [They will be dosed at baseline and after 12 weeks of intervention.]
Fasting blood glucose (mg/dL) will be measured before and after the intervention.
Glycated haemoglobin [They will be dosed at baseline and after 12 weeks of intervention.]
Hb A1c (%) will be measured before and after the intervention.
Insulin [They will be dosed at baseline and after 12 weeks of intervention.]
Insulin (µU/mL) will be measured before and after the intervention.
Serum Iron [They will be dosed at baseline and after 12 weeks of intervention.]
Serum iron (mcg/dL) will be measured before and after intervention.
Transferrin saturation [They will be dosed at baseline and after 12 weeks of intervention.]
Transferrin saturation (%) will be measured before and after intervention.
Serum ferritin [They will be dosed at baseline and after 12 weeks of intervention.]
Serum ferritin will be evaluated in µg/L before and after intervention.
Hepatic transaminases [They will be dosed at baseline and after 12 weeks of intervention.]
Alanine aminotransferase (ALT) and Aspartate Aminotransferase (AST) will be evaluated in U/L before and after intervention.
gamma glutamyl transferase [They will be dosed at baseline and after 12 weeks of intervention.]
Gamma glutamyl transferase will be evaluated in U/L before and after intervention.

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.