<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/NCT02216552</url>
  </required_header>
  <id_info>
    <org_study_id>2013-01-15-RESV</org_study_id>
    <nct_id>NCT02216552</nct_id>
  </id_info>
  <brief_title>Resveratrol for the Treatment of Non Alcoholic Fatty Liver Disease and Insulin Resistance in Overweight Adolescents</brief_title>
  <official_title>Safety and Efficacy of Resveratrol for the Treatment of Non-Alcoholic Fatty Liver Disease and Associated Insulin Resistance in Overweight and Obese Adolescents</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Manitoba</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>DSM Nutritional Products, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Manitoba</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The current project is designed as a 30-day pilot trial to demonstrate the safety and&#xD;
      tolerability of resveratrol therapy in overweight adolescents to decrease liver fat, and&#xD;
      improve insulin sensitivity to prevent type 2 diabetes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Pilot study of 10 overweight or obese children with MRS determined fatty liver randomized to&#xD;
      resveratrol or placebo. Primary outcome measures include change in liver triglyceride content&#xD;
      as determined by MRS and improvement in insulin resistance as determined by the area under&#xD;
      the curve of glucose excursion during a 75 gram oral glucose tolerance test.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2015</start_date>
  <completion_date type="Actual">March 20, 2017</completion_date>
  <primary_completion_date type="Actual">January 1, 2017</primary_completion_date>
  <phase>Phase 2/Phase 3</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>Resveratrol as ResVida (TM) compared to a placebo</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety/ Adverse Event Outcome</measure>
    <time_frame>One week</time_frame>
    <description>Primary Side effect profile determined by participant interview and serum biochemistry. Side effect profile determined by serum biochemistry: AST, ALT, total and conjugated bilirubin, Creatinine, sodium, potassium, calcium, magnesium, chloride and TC02, haemoglobin, haematocrit, white blood cell and platelet counts, erythrocytes, and fasting lipid levels (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides). Fasting glucose and insulin levels. PT/INR and PTT levels.&#xD;
Vital signs</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety/ Adverse Event Outcome</measure>
    <time_frame>Week 2</time_frame>
    <description>Primary Side effect profile determined by participant interview. Side effect profile determined by serum biochemistry: AST, ALT, total and conjugated bilirubin, Creatinine, sodium, potassium, calcium, magnesium, chloride and TC02, haemoglobin, haematocrit, white blood cell and platelet counts, erythrocytes, and fasting lipid levels (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides). Fasting glucose and insulin levels. PT/INR and PTT levels.&#xD;
Vital signs</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety/ Adverse Event Outcome</measure>
    <time_frame>Week 3</time_frame>
    <description>Primary Side effect profile determined by participant interview. Side effect profile determined by serum biochemistry: AST, ALT, total and conjugated bilirubin, Creatinine, sodium, potassium, calcium, magnesium, chloride and TC02, haemoglobin, haematocrit, white blood cell and platelet counts, erythrocytes, and fasting lipid levels (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides). Fasting glucose and insulin levels. PT/INR and PTT levels.&#xD;
Vital signs</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety/ Adverse Event Outcome</measure>
    <time_frame>Week 4</time_frame>
    <description>Primary Side effect profile determined by participant interview. Side effect profile determined by serum biochemistry: AST, ALT, total and conjugated bilirubin, Creatinine, sodium, potassium, calcium, magnesium, chloride and TC02, haemoglobin, haematocrit, white blood cell and platelet counts, erythrocytes, and fasting lipid levels (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides). Fasting glucose and insulin levels. PT/INR and PTT levels.&#xD;
Vital signs</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety/ Adverse Event Outcome</measure>
    <time_frame>Week 8</time_frame>
    <description>Primary Side effect profile determined by participant interview. Side effect profile determined by serum biochemistry: AST, ALT, total and conjugated bilirubin, Creatinine, sodium, potassium, calcium, magnesium, chloride and TC02, haemoglobin, haematocrit, white blood cell and platelet counts, erythrocytes, and fasting lipid levels (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides). Fasting glucose and insulin levels. PT/INR and PTT levels.&#xD;
Vital signs</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Efficacy Outcome</measure>
    <time_frame>Week 4</time_frame>
    <description>To determine efficacy of resveratrol to reduce hepatic and cardiac triglyceride content in adolescents with NAFL MR spectroscopy will be performed using a 3.0-Tesla whole-body magnet. Sixty-four spectra will be acquired and averaged for the determination of intracellular water and lipid content. LCModel software will be used to isolate and quantify lipid and water peaks. Hepatic steatosis will be defined as hepatic triglyceride content of &gt;.5% fat/water.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Efficacy Outcome</measure>
    <time_frame>Week 4</time_frame>
    <description>To determine efficacy of resveratrol to reduce whole body insulin resistance in overweight and obese adolescents with NAFL. The 3-hr frequently sampled oral glucose tolerance test (OGTT) using a standard 75-gram-glucose-load will be performed at the baseline visit and after completion of supplementation (day 30; visit 3). Blood samples will be collected at 20, 30, 60, 90, 120 and 180 minutes after ingestion of glucose will be used for the determination of insulin sensitivity using the Matsuda index</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy Outcome</measure>
    <time_frame>Week 4</time_frame>
    <description>To determine the effects of resveratrol on cardiac function and morphology in the study population. Cardiac function and morphology will be measured using a cardiac ultrasound at baseline (day 0) and at completion of supplementation (day 30; visit 3).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy Outcome</measure>
    <time_frame>Week 1</time_frame>
    <description>To determine the effect of resveratrol supplementation on serum markers of inflammation. Inflammatory markers will be assessed by measurements of circulating adiponectin, leptin, CRP, ESR, TNFalpha, IL-1beta, IL-6, and IL-10, using commercially available ELISA assays.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy Outcome</measure>
    <time_frame>Week 2</time_frame>
    <description>To determine the effect of resveratrol supplementation on serum markers of inflammation. Inflammatory markers will be assessed by measurements of circulating adiponectin, leptin, CRP, ESR, TNFalpha, IL-1beta, IL-6, and IL-10, using commercially available ELISA assays.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy Outcome</measure>
    <time_frame>Week 3</time_frame>
    <description>To determine the effect of resveratrol supplementation on serum markers of inflammation. Inflammatory markers will be assessed by measurements of circulating adiponectin, leptin, CRP, ESR, TNFalpha, IL-1beta, IL-6, and IL-10, using commercially available ELISA assays</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy Outcome</measure>
    <time_frame>Week 4</time_frame>
    <description>To determine the effect of resveratrol supplementation on serum markers of inflammation. Inflammatory markers will be assessed by measurements of circulating adiponectin, leptin, CRP, ESR, TNFalpha, IL-1beta, IL-6, and IL-10, using commercially available ELISA assays</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>NAFLD</condition>
  <condition>TYPE 2 DIABETES</condition>
  <condition>METABOLIC SYNDROME</condition>
  <arm_group>
    <arm_group_label>Resveratrol</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intervention: Resveratrol Oral supplementation of resveratrol (ResVida) 75 mg twice daily (with breakfast and dinner) for a total daily dose of 150 mg for the duration of 30 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Intervention: Placebo Control Oral supplementation of placebo twice daily (with breakfast and dinner) for a total duration of 30 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Resveratrol</intervention_name>
    <description>All adolescents will receive standardized lifestyle counselling at enrolment designed and disseminated by a registered dietitian as well as a licensed physiotherapist who both have experience working with overweight adolescents. The lifestyle component will be goal-based and tailored to each participant. The overall content and messaging will be consistent for all participants with nutritional recommendations based on Canada Food Guide and physical activity counselling aligning with the Healthy Active Living Recommendations of the Canadian Pediatric Society and Health Canada's Physical Activity Guidelines.</description>
    <arm_group_label>Resveratrol</arm_group_label>
    <other_name>ResVida (Registered Trademark of DSM)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>All adolescents will receive standardized lifestyle counselling at enrolment designed and disseminated by a registered dietitian as well as a licensed physiotherapist who both have experience working with overweight adolescents. The lifestyle component will be goal-based and tailored to each participant. The overall content and messaging will be consistent for all participants with nutritional recommendations based on Canada Food Guide and physical activity counselling aligning with the Healthy Active Living Recommendations of the Canadian Pediatric Society and Health Canada's Physical Activity Guidelines.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  13 to &lt;18 years of age&#xD;
&#xD;
          -  BMI considered overweight (BMI &gt; 25 kg/m2 ) or obese (BMI &gt; 30 kg/m2 )&#xD;
&#xD;
          -  Confirmed 1H-MRS defined hepatic steatosis (&gt;5.5% fat/water)&#xD;
&#xD;
          -  Parent/Guardian willing and able to provide written, signed informed consent, and&#xD;
             subjects willing to co-sign parental consent&#xD;
&#xD;
          -  Sexually active subjects must be willing to use an acceptable method of contraception&#xD;
&#xD;
          -  Females of child bearing potential must have a negative pregnancy test at screening.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  The use of any chronic medications with the exception of oral birth control and&#xD;
             natural health products with the exception of multivitamins.&#xD;
&#xD;
          -  Adolescents with altered insulin sensitivity or tissue lipid content unrelated to&#xD;
             obesity and the metabolic syndrome, including:&#xD;
&#xD;
        type 2 diabetes; present or previous malignancy renal disease, hypertension (anyone who has&#xD;
        BPs over the 99th percentile for age and gender) or liver disease;&#xD;
&#xD;
          -  significant weight loss (10% in last six months) or enrolled in weight loss program in&#xD;
             the six months prior to the study;&#xD;
&#xD;
          -  self-reported history of alcohol consumption of greater than two drinks per day and/or&#xD;
             drinking alcohol more than once weekly;&#xD;
&#xD;
          -  report using non-prescription recreational drugs;&#xD;
&#xD;
          -  allergies or sensitivities to any of the ingredients in the investigational product or&#xD;
             placebo;&#xD;
&#xD;
          -  females breastfeeding at screening or planning on becoming pregnant at any time during&#xD;
             the study;&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>13 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Brandy A Wicklow, MD, MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Manitoba</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Hospital Research Institute of Manitoba/University of Manitoba</name>
      <address>
        <city>Winnipeg</city>
        <state>Manitoba</state>
        <zip>R3E 3P4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>August 12, 2014</study_first_submitted>
  <study_first_submitted_qc>August 12, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 15, 2014</study_first_posted>
  <last_update_submitted>May 2, 2017</last_update_submitted>
  <last_update_submitted_qc>May 2, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 5, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Manitoba</investigator_affiliation>
    <investigator_full_name>Dr. Brandy Wicklow</investigator_full_name>
    <investigator_title>Principal Investigator MD</investigator_title>
  </responsible_party>
  <keyword>Pediatrics</keyword>
  <keyword>Adolescents</keyword>
  <keyword>NAFLD</keyword>
  <keyword>Spectroscopy</keyword>
  <keyword>Type 2 diabetes</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>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
    <mesh_term>Overweight</mesh_term>
    <mesh_term>Metabolic Syndrome</mesh_term>
    <mesh_term>Insulin Resistance</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Resveratrol</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/NCT02216552
org study id: 2013-01-15-RESV
nct id: NCT02216552
lead sponsor: 
collaborator: 
has dmc: Yes
The current project is designed as a 30-day pilot trial to demonstrate the safety and
      tolerability of resveratrol therapy in overweight adolescents to decrease liver fat, and
      improve insulin sensitivity to prevent type 2 diabetes.
Pilot study of 10 overweight or obese children with MRS determined fatty liver randomized to
      resveratrol or placebo. Primary outcome measures include change in liver triglyceride content
      as determined by MRS and improvement in insulin resistance as determined by the area under
      the curve of glucose excursion during a 75 gram oral glucose tolerance test.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Resveratrol as ResVida (TM) compared to a placebo
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Safety/ Adverse Event Outcome
time frame: One week
description: Primary Side effect profile determined by participant interview and serum biochemistry. Side effect profile determined by serum biochemistry: AST, ALT, total and conjugated bilirubin, Creatinine, sodium, potassium, calcium, magnesium, chloride and TC02, haemoglobin, haematocrit, white blood cell and platelet counts, erythrocytes, and fasting lipid levels (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides). Fasting glucose and insulin levels. PT/INR and PTT levels.
Vital signs
measure: Safety/ Adverse Event Outcome
time frame: Week 2
description: Primary Side effect profile determined by participant interview. Side effect profile determined by serum biochemistry: AST, ALT, total and conjugated bilirubin, Creatinine, sodium, potassium, calcium, magnesium, chloride and TC02, haemoglobin, haematocrit, white blood cell and platelet counts, erythrocytes, and fasting lipid levels (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides). Fasting glucose and insulin levels. PT/INR and PTT levels.
Vital signs
measure: Safety/ Adverse Event Outcome
time frame: Week 3
description: Primary Side effect profile determined by participant interview. Side effect profile determined by serum biochemistry: AST, ALT, total and conjugated bilirubin, Creatinine, sodium, potassium, calcium, magnesium, chloride and TC02, haemoglobin, haematocrit, white blood cell and platelet counts, erythrocytes, and fasting lipid levels (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides). Fasting glucose and insulin levels. PT/INR and PTT levels.
Vital signs
measure: Safety/ Adverse Event Outcome
time frame: Week 4
description: Primary Side effect profile determined by participant interview. Side effect profile determined by serum biochemistry: AST, ALT, total and conjugated bilirubin, Creatinine, sodium, potassium, calcium, magnesium, chloride and TC02, haemoglobin, haematocrit, white blood cell and platelet counts, erythrocytes, and fasting lipid levels (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides). Fasting glucose and insulin levels. PT/INR and PTT levels.
Vital signs
measure: Safety/ Adverse Event Outcome
time frame: Week 8
description: Primary Side effect profile determined by participant interview. Side effect profile determined by serum biochemistry: AST, ALT, total and conjugated bilirubin, Creatinine, sodium, potassium, calcium, magnesium, chloride and TC02, haemoglobin, haematocrit, white blood cell and platelet counts, erythrocytes, and fasting lipid levels (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides). Fasting glucose and insulin levels. PT/INR and PTT levels.
Vital signs
measure: Efficacy Outcome
time frame: Week 4
description: To determine efficacy of resveratrol to reduce hepatic and cardiac triglyceride content in adolescents with NAFL MR spectroscopy will be performed using a 3.0-Tesla whole-body magnet. Sixty-four spectra will be acquired and averaged for the determination of intracellular water and lipid content. LCModel software will be used to isolate and quantify lipid and water peaks. Hepatic steatosis will be defined as hepatic triglyceride content of >.5% fat/water.
measure: Efficacy Outcome
time frame: Week 4
description: To determine efficacy of resveratrol to reduce whole body insulin resistance in overweight and obese adolescents with NAFL. The 3-hr frequently sampled oral glucose tolerance test (OGTT) using a standard 75-gram-glucose-load will be performed at the baseline visit and after completion of supplementation (day 30; visit 3). Blood samples will be collected at 20, 30, 60, 90, 120 and 180 minutes after ingestion of glucose will be used for the determination of insulin sensitivity using the Matsuda index
measure: Efficacy Outcome
time frame: Week 4
description: To determine the effects of resveratrol on cardiac function and morphology in the study population. Cardiac function and morphology will be measured using a cardiac ultrasound at baseline (day 0) and at completion of supplementation (day 30; visit 3).
measure: Efficacy Outcome
time frame: Week 1
description: To determine the effect of resveratrol supplementation on serum markers of inflammation. Inflammatory markers will be assessed by measurements of circulating adiponectin, leptin, CRP, ESR, TNFalpha, IL-1beta, IL-6, and IL-10, using commercially available ELISA assays.
measure: Efficacy Outcome
time frame: Week 2
description: To determine the effect of resveratrol supplementation on serum markers of inflammation. Inflammatory markers will be assessed by measurements of circulating adiponectin, leptin, CRP, ESR, TNFalpha, IL-1beta, IL-6, and IL-10, using commercially available ELISA assays.
measure: Efficacy Outcome
time frame: Week 3
description: To determine the effect of resveratrol supplementation on serum markers of inflammation. Inflammatory markers will be assessed by measurements of circulating adiponectin, leptin, CRP, ESR, TNFalpha, IL-1beta, IL-6, and IL-10, using commercially available ELISA assays
measure: Efficacy Outcome
time frame: Week 4
description: To determine the effect of resveratrol supplementation on serum markers of inflammation. Inflammatory markers will be assessed by measurements of circulating adiponectin, leptin, CRP, ESR, TNFalpha, IL-1beta, IL-6, and IL-10, using commercially available ELISA assays
arm group label: Resveratrol
arm group type: Experimental
description: Intervention: Resveratrol Oral supplementation of resveratrol (ResVida) 75 mg twice daily (with breakfast and dinner) for a total daily dose of 150 mg for the duration of 30 days.
arm group label: Placebo
arm group type: Placebo Comparator
description: Intervention: Placebo Control Oral supplementation of placebo twice daily (with breakfast and dinner) for a total duration of 30 days.
intervention type: Dietary Supplement
intervention name: Resveratrol
description: All adolescents will receive standardized lifestyle counselling at enrolment designed and disseminated by a registered dietitian as well as a licensed physiotherapist who both have experience working with overweight adolescents. The lifestyle component will be goal-based and tailored to each participant. The overall content and messaging will be consistent for all participants with nutritional recommendations based on Canada Food Guide and physical activity counselling aligning with the Healthy Active Living Recommendations of the Canadian Pediatric Society and Health Canada's Physical Activity Guidelines.
arm group label: Resveratrol
other name: ResVida (Registered Trademark of DSM)
intervention type: Dietary Supplement
intervention name: Placebo
description: All adolescents will receive standardized lifestyle counselling at enrolment designed and disseminated by a registered dietitian as well as a licensed physiotherapist who both have experience working with overweight adolescents. The lifestyle component will be goal-based and tailored to each participant. The overall content and messaging will be consistent for all participants with nutritional recommendations based on Canada Food Guide and physical activity counselling aligning with the Healthy Active Living Recommendations of the Canadian Pediatric Society and Health Canada's Physical Activity Guidelines.
arm group label: Placebo
criteria: 
gender: All
minimum age: 13 Years
maximum age: 18 Years
healthy volunteers: No
last name: Brandy A Wicklow, MD, MSc
role: Principal Investigator
affiliation: University of Manitoba
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: University of Manitoba
investigator full name: Dr. Brandy Wicklow
investigator title: Principal Investigator MD
mesh term: Liver Diseases
mesh term: Fatty Liver
mesh term: Non-alcoholic Fatty Liver Disease
mesh term: Diabetes Mellitus, Type 2
mesh term: Overweight
mesh term: Metabolic Syndrome
mesh term: Insulin Resistance
mesh term: Resveratrol
sharing ipd: No