<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03749070</url>
  </required_header>
  <id_info>
    <org_study_id>2.635.954</org_study_id>
    <nct_id>NCT03749070</nct_id>
  </id_info>
  <brief_title>Efficacy of Silymarin in Patients With Non-alcoholic Fatty Liver Disease - The SILIVER Trial</brief_title>
  <official_title>Efficacy of Silymarin in Patients With Non-alcoholic Fatty Liver Disease - The SILIVER Trial: Randomized Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Camila Ribeiro de Avelar</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital Universitário Professor Edgard Santos</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Non-Alcoholic Fatty Liver Disease (NAFLD) is one of the most prevalent chronic liver diseases&#xD;
      in Brazil and its treatment is still limited. Thus, this project aims to conduct a&#xD;
      double-blind, controlled, randomized clinical trial to evaluate the effect of silymarin on&#xD;
      laboratory markers and clinical evolution of adult patients with NAFLD treated at Edgard&#xD;
      Santos Hospital, as well as identify the dietary pattern of these individuals.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Non-Alcoholic Fatty Liver Disease (NAFLD) is one of the most prevalent chronic liver diseases&#xD;
      in Brazil. It has a significantly increasing incidence today and is considered an important&#xD;
      global health problem. It affects approximately 20 to 30% of the adult population and&#xD;
      increases according to the severity of the risk factors. The diagnosis of this disease&#xD;
      usually occurs in 10 to 20% of the non-obese individuals, 50% in the overweight and 80 to 90%&#xD;
      in the obese, being twice as present in individuals with Metabolic Syndrome. Pharmacological&#xD;
      treatment options for NAFLD are still limited and Silybum marianum, one of the most&#xD;
      sought-after herbal remedies in patients with liver disease, is commonly used by patients&#xD;
      because of the claim of the hepatoprotective effect of silymarin. Studies have demonstrated&#xD;
      the therapeutic potential of silymarin in patients with NAFLD, but clinical trials with more&#xD;
      judicious methodological designs is still needed to prove these effects. Thus, this project&#xD;
      aims to evaluate the efficacy of silymarin in adult patients with NAFLD seen at the Clinic of&#xD;
      Nutrition and Hepatology of Edgard Santos Hospital. A randomized, double-blind, controlled&#xD;
      clinical trial lasting 12 weeks will be performed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 15, 2019</start_date>
  <completion_date type="Anticipated">August 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">August 31, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Clinical trial, randomized, double-blind and controlled</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Double-blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Absence or change in NAFLD degree</measure>
    <time_frame>They will be dosed at baseline and after 12 weeks of intervention.</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Lipid profile</measure>
    <time_frame>They will be dosed at baseline and after 12 weeks of intervention.</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fasting blood glucose</measure>
    <time_frame>They will be dosed at baseline and after 12 weeks of intervention.</time_frame>
    <description>Fasting blood glucose (mg/dL) will be measured before and after the intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glycated haemoglobin</measure>
    <time_frame>They will be dosed at baseline and after 12 weeks of intervention.</time_frame>
    <description>Hb A1c (%) will be measured before and after the intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Insulin</measure>
    <time_frame>They will be dosed at baseline and after 12 weeks of intervention.</time_frame>
    <description>Insulin (µU/mL) will be measured before and after the intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Iron</measure>
    <time_frame>They will be dosed at baseline and after 12 weeks of intervention.</time_frame>
    <description>Serum iron (mcg/dL) will be measured before and after intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Transferrin saturation</measure>
    <time_frame>They will be dosed at baseline and after 12 weeks of intervention.</time_frame>
    <description>Transferrin saturation (%) will be measured before and after intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum ferritin</measure>
    <time_frame>They will be dosed at baseline and after 12 weeks of intervention.</time_frame>
    <description>Serum ferritin will be evaluated in µg/L before and after intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hepatic transaminases</measure>
    <time_frame>They will be dosed at baseline and after 12 weeks of intervention.</time_frame>
    <description>Alanine aminotransferase (ALT) and Aspartate Aminotransferase (AST) will be evaluated in U/L before and after intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>gamma glutamyl transferase</measure>
    <time_frame>They will be dosed at baseline and after 12 weeks of intervention.</time_frame>
    <description>Gamma glutamyl transferase will be evaluated in U/L before and after intervention.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">132</enrollment>
  <condition>Non-Alcoholic Fatty Liver Disease</condition>
  <arm_group>
    <arm_group_label>Silymarin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Silymarin</intervention_name>
    <description>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.</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Silymarin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults between 20 and 60 years of age, both men and women,&#xD;
&#xD;
          -  Clinical diagnosis of NAFLD, confirmed by imaging exams,&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women in the menacing period, with the exception of those who have performed&#xD;
             definitive sterilization, such as hysterectomy or tubal ligation.&#xD;
&#xD;
          -  Patients with established prior diagnosis of chronic noncommunicable disease&#xD;
             (congestive heart failure, decompensated or severe lung disease, neoplasms, renal&#xD;
             disease, advanced liver disease - Child Pugh C classification)&#xD;
&#xD;
          -  Patients with schistosomiasis;&#xD;
&#xD;
          -  Hemochromatosis&#xD;
&#xD;
          -  Wilson's disease&#xD;
&#xD;
          -  Viral or autoimmune hepatitis&#xD;
&#xD;
          -  HIV virus carriers&#xD;
&#xD;
          -  Woman who is breastfeeding&#xD;
&#xD;
          -  Users of illicit drugs&#xD;
&#xD;
          -  Patients with an intake of more than 20 g / day of alcohol and / or past alcoholism&#xD;
             with abstention less than 6 months;&#xD;
&#xD;
          -  Patients with ingestion of medications such as steroids, estrogens, amiodarone,&#xD;
             warfarin, anti-convulsants, antipsychotics, tamoxifen or other chemotherapeutic agents&#xD;
             in the last 6 months&#xD;
&#xD;
          -  Patients with clinically manifest infections or inflammation, surgery, trauma or&#xD;
             hospitalization in the last 30 days&#xD;
&#xD;
          -  Chronic non-hepatic degenerative diseases (sclerosis, Parkinson's disease or&#xD;
             Alzheimer's disease)&#xD;
&#xD;
          -  Patients who do not participate in all stages of the research.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Camila Avelar</last_name>
    <phone>+55 (71)991540434</phone>
    <phone_ext>+55</phone_ext>
    <email>contato@camilaavelar.com.br</email>
  </overall_contact>
  <location>
    <facility>
      <name>Camila Ribeiro de Avelar</name>
      <address>
        <city>Salvador</city>
        <state>Bahia</state>
        <zip>40.110.060</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Camila Avelar</last_name>
      <phone>+55(71)991540434</phone>
      <email>contato@camilaavelar.com.br</email>
    </contact>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>October 28, 2018</study_first_submitted>
  <study_first_submitted_qc>November 19, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 21, 2018</study_first_posted>
  <last_update_submitted>August 1, 2022</last_update_submitted>
  <last_update_submitted_qc>August 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Hospital Universitário Professor Edgard Santos</investigator_affiliation>
    <investigator_full_name>Camila Ribeiro de Avelar</investigator_full_name>
    <investigator_title>Doctor student</investigator_title>
  </responsible_party>
  <keyword>Non-Alcoholic Fatty Liver Disease</keyword>
  <keyword>sylimarin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Diseases</mesh_term>
    <mesh_term>Fatty Liver</mesh_term>
    <mesh_term>Non-alcoholic Fatty Liver Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Silymarin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03749070
org study id: 2.635.954
nct id: NCT03749070
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Clinical trial, randomized, double-blind and controlled
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Double-blind
measure: Absence or change in NAFLD degree
time frame: They will be dosed at baseline and after 12 weeks of intervention.
description: 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.
measure: Lipid profile
time frame: They will be dosed at baseline and after 12 weeks of intervention.
description: 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.
measure: Fasting blood glucose
time frame: They will be dosed at baseline and after 12 weeks of intervention.
description: Fasting blood glucose (mg/dL) will be measured before and after the intervention.
measure: Glycated haemoglobin
time frame: They will be dosed at baseline and after 12 weeks of intervention.
description: Hb A1c (%) will be measured before and after the intervention.
measure: Insulin
time frame: They will be dosed at baseline and after 12 weeks of intervention.
description: Insulin (µU/mL) will be measured before and after the intervention.
measure: Serum Iron
time frame: They will be dosed at baseline and after 12 weeks of intervention.
description: Serum iron (mcg/dL) will be measured before and after intervention.
measure: Transferrin saturation
time frame: They will be dosed at baseline and after 12 weeks of intervention.
description: Transferrin saturation (%) will be measured before and after intervention.
measure: Serum ferritin
time frame: They will be dosed at baseline and after 12 weeks of intervention.
description: Serum ferritin will be evaluated in µg/L before and after intervention.
measure: Hepatic transaminases
time frame: They will be dosed at baseline and after 12 weeks of intervention.
description: Alanine aminotransferase (ALT) and Aspartate Aminotransferase (AST) will be evaluated in U/L before and after intervention.
measure: gamma glutamyl transferase
time frame: They will be dosed at baseline and after 12 weeks of intervention.
description: Gamma glutamyl transferase will be evaluated in U/L before and after intervention.
arm group label: Silymarin
arm group type: Active Comparator
description: 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.
arm group label: Placebo
arm group type: Placebo Comparator
description: 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.
intervention type: Dietary Supplement
intervention name: Silymarin
description: 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 group label: Placebo
arm group label: Silymarin
criteria: 
gender: All
minimum age: 20 Years
maximum age: 60 Years
healthy volunteers: No
last name: Camila Avelar
phone: +55 (71)991540434
phone ext: +55
email: contato@camilaavelar.com.br
facility: 
status: Recruiting
contact: 
country: Brazil
responsible party type: Sponsor-Investigator
investigator affiliation: Hospital Universitário Professor Edgard Santos
investigator full name: Camila Ribeiro de Avelar
investigator title: Doctor student
mesh term: Liver Diseases
mesh term: Fatty Liver
mesh term: Non-alcoholic Fatty Liver Disease
mesh term: Silymarin
sharing ipd: No