<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/NCT02201160</url>
  </required_header>
  <id_info>
    <org_study_id>NAFLD-2188</org_study_id>
    <nct_id>NCT02201160</nct_id>
  </id_info>
  <brief_title>Potential Role of n-3 Fatty Acids in the Treatment of NAFLD in Pediatric Patients</brief_title>
  <official_title>Impact of n-3 Fatty Acid Supplementation on the Metabolic Abnormalities in Children With NAFLD</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>St. Justine's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Nutrisanté Canada</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>St. Justine's Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Nonalcoholic hepatic steatosis (NASH) is defined as the amount greater than 5% of the total&#xD;
      liver volume fat. Commonly known as NASH, it includes 4 stages histological ranging from the&#xD;
      mere presence of fat to the existence of fibrosis and degeneration of hepatocytes, and&#xD;
      finally a progression to cirrhosis, sometimes accompanied by complications of hepatocellular&#xD;
      carcinoma. It is a common condition associated with a combination of disorders, namely&#xD;
      obesity, insulin resistance and type 2 diabetes. The link with the metabolic syndrome (MetS)&#xD;
      was mainly studied in the adult population and very little in the paediatric population,&#xD;
      while 15 and 25% of obese children are affectés. The severity of histological disease appears&#xD;
      to be associated with the degree of obesity in children and particularly in the MetS. in&#xD;
      addition, epidemiological data indicate that the incidence of this disease is increasing in&#xD;
      children and positioning as the first NASH liver disease in North America. the revelation of&#xD;
      the factors associated with the occurrence of NASH is a first necessary step to understanding&#xD;
      this disorder worrying for the future of children and adolescents. In addition, clarification&#xD;
      of the mechanisms responsible for its development is essential if the investigators want to&#xD;
      consider targeted and effective treatments to slow the rat race of NASH, which stands out as&#xD;
      the supreme chronic liver accompanying the obesity and MetS. Finally, in view of growth and&#xD;
      puberty of children, it would be extremely beneficial to find nutritional avenues that would&#xD;
      avoid the side effects of chemical agents.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The aims of the investigators studies are to determine the plasma FA composition and to&#xD;
      assess changes in the latter in response to n-3 supplementation in French-Canadian youth&#xD;
      since (i) none of the available pharmacological agents could be recommended for treatment of&#xD;
      children with NAFLD; (ii) n-3 PUFA are quite safe diet supplements that showed efficacy in&#xD;
      the prevention and therapy of cardiovascular diseases, dyslipidemia and metabolic syndrome;&#xD;
      (iii) loss of n-3 PUFA dietary intake was found in pediatric NAFLD and (iii) no attention has&#xD;
      been given to French-Canadian population, which is primarily and historically located in the&#xD;
      province of Quebec, has the highest prevalence worldwide of lipoprotein lipase deficiency,&#xD;
      includes a large pool of individuals at risk for atherosclerosis and other lipid-related&#xD;
      diseases, and exhibits a founder effect among the 8,000 ancestors of present-day&#xD;
      French-Canadians, who have had relatively little cross-breeding with individuals from other&#xD;
      national origin groups.&#xD;
&#xD;
      Subjects The present randomized clinical trial was performed on 30 NAFLD children followed as&#xD;
      outpatients at the Gastroenterology/Hepatology and Nutrition clinic of MCHU Ste-Justine and&#xD;
      the Gastroenterology division of the Montreal Children's Hospital, Montreal.&#xD;
&#xD;
      The children have between 8 years and 18 years of age, with obesity and a diagnostic of NAFLD&#xD;
      based on the results of a clinical evaluation, liver echography, and magnetic resonance&#xD;
      imaging-proton density fat fraction.&#xD;
&#xD;
      Inclusion and exclusion criteria The children are eligible for the study if they are boys&#xD;
      (according to the literature review on NAFLD prevalence), with a body weight ≥ 95th&#xD;
      percentile (based on the CDC Chart), aged &lt;18 years, have a diffusely hyperechogenic liver at&#xD;
      ultrasonography (consistent with NAFLD diagnostic), and have normal or high transaminases (&gt;&#xD;
      2N). Moreover, the exclusion criteria is based on subjects having pin or cochlear implants&#xD;
      may affect the magnetic resonance imaging examination; subjects who consumed natural medicine&#xD;
      products have an increased risk of haemorrhage, and those in whom a surgical procedure was&#xD;
      planned, and the child who founded to consume fish, flaxseed oil and foods enriched with n-3&#xD;
      PUFA (eggs, or milk containing n-3 PUFA supplements), probiotics, vitamin E or use of drugs&#xD;
      known to induce fatty liver during the study.&#xD;
&#xD;
      Study design The present study is a 6-month, double-blind, one-way, crossover randomized&#xD;
      study. The treatment consisting of n-3 PUFA supplement (NutriSanté Inc./Ponroy, Canada),&#xD;
      administered in two phases, each of 3-month duration. In the first phase, an NAFLD group will&#xD;
      receive an active n-3 PUFA supplement and another will receive equivalent quantities of&#xD;
      sunflower oil as a placebo. During the second phase (after the first 3 months), all NAFLD&#xD;
      subjects will receive an active n-3 PUFA. The study is approved by the Clinical Research&#xD;
      Ethics Committee of MUCH Ste-Justine (Montreal, Quebec. Informed consent was obtained from&#xD;
      all subjects before starting experimental procedures, and the study followed the Helsinki&#xD;
      guidelines.&#xD;
&#xD;
      Dosing The dose supplementation considered for this study is 2.0 g of fish oil per day,&#xD;
      providing a total of 1.2 g of n-3 PUFA. This dose is chosen according to official&#xD;
      recommendations, based on our previous studies and pediatric clinical trials. Compliance to&#xD;
      the study treatment will be evaluated by pill count at every visit, review of medication&#xD;
      records, and direct interview of patients by the physician.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>January 2009</start_date>
  <completion_date type="Anticipated">December 2015</completion_date>
  <primary_completion_date type="Actual">December 2013</primary_completion_date>
  <phase>Phase 1/Phase 2</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Efficacy of omega 3 PUFA supplementation in NAFLD subjects compared to placebos</measure>
    <time_frame>24 weeks</time_frame>
    <description>Two groups from our cohort will be double blind supplemented either with n-3 PUFA or sun flower (as a placebo).&#xD;
The specific primary outcome is to assess the activities of hepatic plasma transaminase enzymes (ALT/AST/GGT) in the omega 3 group and to determine their decrease to the normal range.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>A composite mesures regarding the improvement of metabolic profile of NAFLD patients</measure>
    <time_frame>24 weeks</time_frame>
    <description>To determine&#xD;
the decrease in obesity (body mass index)&#xD;
insulin resistance (HOMA-IR)&#xD;
Adipose tissue lowering (DEXA)&#xD;
Oxidative stress (Malondialdehyde biomarker, oxLDL) Inflammation (TNFalpha, IL-6, leptin and resistine)&#xD;
Plasma lipids (triglycerides, total cholesterol, LDL and HDL cholesterol)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Short term versus long-term treatment comparison</measure>
    <time_frame>12 weeks vs. 24 weeks</time_frame>
    <description>To compare the effectiveness of omega 3 PUFA between 12- and 24-weeks by a composite measures in terms of percent decrease in the&#xD;
transaminases (ALT/AST/GGT)&#xD;
body weight (BMI)&#xD;
Insulin resistance (HOMA-IR)&#xD;
Oxidative stress (malondialdehyde marker)&#xD;
Inflammation (TNF-alpha, interleukin-6, leptin and resistin)&#xD;
Lipids (triglycerides, cholesterol, LDL-cholesterol, HDL-cholesterol)&#xD;
changes in adipose tissue (DEXA)</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Non Alcoholic Fatty Liver Disease (NAFLD)</condition>
  <arm_group>
    <arm_group_label>omega 3</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The subjects will take 4 capsules/day during 6 months. Each capsule of the active n-3 PUFA supplement contained 500 mg of fish oil (each capsule provides 300 mg of n-3 PUFA (EPA+DHA) with 3.75 U vitamin E to prevent peroxidation).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sun Flower</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The subjects will take 4 capsules/day during 6 months. The placebo capsule contained 500 mg of sunflower oil with 3.75 U vitamin E.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>omega 3</intervention_name>
    <description>Two groups from our cohort will be supplemented either with omega-3 PUFA or placebo during 3 months. Each subject will take 4 capsules/d. after 3 months, the subjects under omega-3 will continue for another 3 months and the group under placebo will take omega-3 PUFA during another 3 months.</description>
    <arm_group_label>Sun Flower</arm_group_label>
    <arm_group_label>omega 3</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  boys (according to the literature review on NAFLD prevalence)&#xD;
&#xD;
          -  body weight ≥ 95th percentile (based on the CDC Chart)&#xD;
&#xD;
          -  aged &lt;18 years&#xD;
&#xD;
          -  have a diffusely hyperechogenic liver at ultrasonography (consistent with NAFLD&#xD;
             diagnostic)&#xD;
&#xD;
          -  have normal or high transaminases (&gt; 2N).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with pin or cochlear implants&#xD;
&#xD;
          -  Subjects who consumed natural medicine products&#xD;
&#xD;
          -  Those in whom a surgical procedure was planned&#xD;
&#xD;
          -  the child who were found to consume fish, flaxseed oil and foods enriched with n-3&#xD;
             PUFA (eggs, or milk containing n-3 PUFA supplements), probiotics, vitamin E or use of&#xD;
             drugs known to induce fatty liver during the study.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>8 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Emile Levy, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Research Centre, CHU STe-Justine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHU Ste-Justine</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3T 1C5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <reference>
    <citation>Belanger SA, Vanasse M, Spahis S, Sylvestre MP, Lippe S, L'heureux F, Ghadirian P, Vanasse CM, Levy E. Omega-3 fatty acid treatment of children with attention-deficit hyperactivity disorder: A randomized, double-blind, placebo-controlled study. Paediatr Child Health. 2009 Feb;14(2):89-98. doi: 10.1093/pch/14.2.89.</citation>
    <PMID>19436468</PMID>
  </reference>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>July 18, 2014</study_first_submitted>
  <study_first_submitted_qc>July 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 25, 2014</study_first_posted>
  <last_update_submitted>July 23, 2014</last_update_submitted>
  <last_update_submitted_qc>July 23, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 25, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>St. Justine's Hospital</investigator_affiliation>
    <investigator_full_name>Emile Levy</investigator_full_name>
    <investigator_title>Full professor and researcher</investigator_title>
  </responsible_party>
  <keyword>NAFLD</keyword>
  <keyword>Fatty acid composition</keyword>
  <keyword>Omega 3 supplementation</keyword>
  <keyword>Metabolism</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>
  <!-- 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/NCT02201160
org study id: NAFLD-2188
nct id: NCT02201160
lead sponsor: 
collaborator: 
has dmc: Yes
Nonalcoholic hepatic steatosis (NASH) is defined as the amount greater than 5% of the total
      liver volume fat. Commonly known as NASH, it includes 4 stages histological ranging from the
      mere presence of fat to the existence of fibrosis and degeneration of hepatocytes, and
      finally a progression to cirrhosis, sometimes accompanied by complications of hepatocellular
      carcinoma. It is a common condition associated with a combination of disorders, namely
      obesity, insulin resistance and type 2 diabetes. The link with the metabolic syndrome (MetS)
      was mainly studied in the adult population and very little in the paediatric population,
      while 15 and 25% of obese children are affectés. The severity of histological disease appears
      to be associated with the degree of obesity in children and particularly in the MetS. in
      addition, epidemiological data indicate that the incidence of this disease is increasing in
      children and positioning as the first NASH liver disease in North America. the revelation of
      the factors associated with the occurrence of NASH is a first necessary step to understanding
      this disorder worrying for the future of children and adolescents. In addition, clarification
      of the mechanisms responsible for its development is essential if the investigators want to
      consider targeted and effective treatments to slow the rat race of NASH, which stands out as
      the supreme chronic liver accompanying the obesity and MetS. Finally, in view of growth and
      puberty of children, it would be extremely beneficial to find nutritional avenues that would
      avoid the side effects of chemical agents.
The aims of the investigators studies are to determine the plasma FA composition and to
      assess changes in the latter in response to n-3 supplementation in French-Canadian youth
      since (i) none of the available pharmacological agents could be recommended for treatment of
      children with NAFLD; (ii) n-3 PUFA are quite safe diet supplements that showed efficacy in
      the prevention and therapy of cardiovascular diseases, dyslipidemia and metabolic syndrome;
      (iii) loss of n-3 PUFA dietary intake was found in pediatric NAFLD and (iii) no attention has
      been given to French-Canadian population, which is primarily and historically located in the
      province of Quebec, has the highest prevalence worldwide of lipoprotein lipase deficiency,
      includes a large pool of individuals at risk for atherosclerosis and other lipid-related
      diseases, and exhibits a founder effect among the 8,000 ancestors of present-day
      French-Canadians, who have had relatively little cross-breeding with individuals from other
      national origin groups.

      Subjects The present randomized clinical trial was performed on 30 NAFLD children followed as
      outpatients at the Gastroenterology/Hepatology and Nutrition clinic of MCHU Ste-Justine and
      the Gastroenterology division of the Montreal Children's Hospital, Montreal.

      The children have between 8 years and 18 years of age, with obesity and a diagnostic of NAFLD
      based on the results of a clinical evaluation, liver echography, and magnetic resonance
      imaging-proton density fat fraction.

      Inclusion and exclusion criteria The children are eligible for the study if they are boys
      (according to the literature review on NAFLD prevalence), with a body weight ≥ 95th
      percentile (based on the CDC Chart), aged <18 years, have a diffusely hyperechogenic liver at
      ultrasonography (consistent with NAFLD diagnostic), and have normal or high transaminases (>
      2N). Moreover, the exclusion criteria is based on subjects having pin or cochlear implants
      may affect the magnetic resonance imaging examination; subjects who consumed natural medicine
      products have an increased risk of haemorrhage, and those in whom a surgical procedure was
      planned, and the child who founded to consume fish, flaxseed oil and foods enriched with n-3
      PUFA (eggs, or milk containing n-3 PUFA supplements), probiotics, vitamin E or use of drugs
      known to induce fatty liver during the study.

      Study design The present study is a 6-month, double-blind, one-way, crossover randomized
      study. The treatment consisting of n-3 PUFA supplement (NutriSanté Inc./Ponroy, Canada),
      administered in two phases, each of 3-month duration. In the first phase, an NAFLD group will
      receive an active n-3 PUFA supplement and another will receive equivalent quantities of
      sunflower oil as a placebo. During the second phase (after the first 3 months), all NAFLD
      subjects will receive an active n-3 PUFA. The study is approved by the Clinical Research
      Ethics Committee of MUCH Ste-Justine (Montreal, Quebec. Informed consent was obtained from
      all subjects before starting experimental procedures, and the study followed the Helsinki
      guidelines.

      Dosing The dose supplementation considered for this study is 2.0 g of fish oil per day,
      providing a total of 1.2 g of n-3 PUFA. This dose is chosen according to official
      recommendations, based on our previous studies and pediatric clinical trials. Compliance to
      the study treatment will be evaluated by pill count at every visit, review of medication
      records, and direct interview of patients by the physician.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Efficacy of omega 3 PUFA supplementation in NAFLD subjects compared to placebos
time frame: 24 weeks
description: Two groups from our cohort will be double blind supplemented either with n-3 PUFA or sun flower (as a placebo).
The specific primary outcome is to assess the activities of hepatic plasma transaminase enzymes (ALT/AST/GGT) in the omega 3 group and to determine their decrease to the normal range.
measure: A composite mesures regarding the improvement of metabolic profile of NAFLD patients
time frame: 24 weeks
description: To determine
the decrease in obesity (body mass index)
insulin resistance (HOMA-IR)
Adipose tissue lowering (DEXA)
Oxidative stress (Malondialdehyde biomarker, oxLDL) Inflammation (TNFalpha, IL-6, leptin and resistine)
Plasma lipids (triglycerides, total cholesterol, LDL and HDL cholesterol)
measure: Short term versus long-term treatment comparison
time frame: 12 weeks vs. 24 weeks
description: To compare the effectiveness of omega 3 PUFA between 12- and 24-weeks by a composite measures in terms of percent decrease in the
transaminases (ALT/AST/GGT)
body weight (BMI)
Insulin resistance (HOMA-IR)
Oxidative stress (malondialdehyde marker)
Inflammation (TNF-alpha, interleukin-6, leptin and resistin)
Lipids (triglycerides, cholesterol, LDL-cholesterol, HDL-cholesterol)
changes in adipose tissue (DEXA)
arm group label: omega 3
arm group type: Active Comparator
description: The subjects will take 4 capsules/day during 6 months. Each capsule of the active n-3 PUFA supplement contained 500 mg of fish oil (each capsule provides 300 mg of n-3 PUFA (EPA+DHA) with 3.75 U vitamin E to prevent peroxidation).
arm group label: Sun Flower
arm group type: Placebo Comparator
description: The subjects will take 4 capsules/day during 6 months. The placebo capsule contained 500 mg of sunflower oil with 3.75 U vitamin E.
intervention type: Dietary Supplement
intervention name: omega 3
description: Two groups from our cohort will be supplemented either with omega-3 PUFA or placebo during 3 months. Each subject will take 4 capsules/d. after 3 months, the subjects under omega-3 will continue for another 3 months and the group under placebo will take omega-3 PUFA during another 3 months.
arm group label: Sun Flower
arm group label: omega 3
criteria: 
gender: Male
minimum age: 8 Years
maximum age: 18 Years
healthy volunteers: No
last name: Emile Levy, Professor
role: Principal Investigator
affiliation: Research Centre, CHU STe-Justine
facility: 
country: Canada
citation: Belanger SA, Vanasse M, Spahis S, Sylvestre MP, Lippe S, L'heureux F, Ghadirian P, Vanasse CM, Levy E. Omega-3 fatty acid treatment of children with attention-deficit hyperactivity disorder: A randomized, double-blind, placebo-controlled study. Paediatr Child Health. 2009 Feb;14(2):89-98. doi: 10.1093/pch/14.2.89.
PMID: 19436468
responsible party type: Principal Investigator
investigator affiliation: St. Justine's Hospital
investigator full name: Emile Levy
investigator title: Full professor and researcher
mesh term: Liver Diseases
mesh term: Fatty Liver
mesh term: Non-alcoholic Fatty Liver Disease