<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/NCT02986672</url>
  </required_header>
  <id_info>
    <org_study_id>ADHD_Kvernmo</org_study_id>
    <nct_id>NCT02986672</nct_id>
  </id_info>
  <brief_title>Intervention With Omega-3 in Children With Attention Deficit Hyperactivity Disorder(ADHD)</brief_title>
  <official_title>ADHD and Nutrition: The Influence of Omega-3 on ADHD Related Symptoms</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital of North Norway</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital of North Norway</source>
  <oversight_info>
    <has_dmc>No</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>
      This study aim to evaluate the effect of marine monounsaturated and polyunsaturated fatty&#xD;
      acids on children aged from 6-16 years, with ADHD/ADD and related symptoms. The study is a&#xD;
      randomized, double-blind placebo-control study including approximately 330 children from&#xD;
      Norway. The primary outcome measure is ADHD core symptoms reported by caregivers, teachers&#xD;
      and the child at 0 months (baseline), 6 months (end of treatment) and 12 months (6 months&#xD;
      post treatment). The secondary outcome measures are reading and writing disabilities,&#xD;
      cognitive functions, and physical Health.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Children with ADHD are shown to have low blood levels of omega-3 fatty acids, not related to&#xD;
      diet. Low levels of omega-3 has also been directly related to poor cognition and behavior.&#xD;
      Trials have shown that supplement with omega-3 may improve literacy and behavior in children&#xD;
      with ADHD symptoms. It has also been shown to improve both memory and reaction time. The&#xD;
      effect sizes found in meta analysis of placebo- controlled clinical trials on ADHD core&#xD;
      symptoms are small to modest. In a study of adolescent mental health in North Norway in&#xD;
      2003-2005 a significant association was found between intake of fish and hyperactivity as&#xD;
      adolescents with a high intake showed less hyperactivity than peers with a low intake&#xD;
      (unpublished results from The Norwegian Arctic Adolescent Health Study, Siv Kvernmo).&#xD;
&#xD;
      There are several key limitations to the existing studies. Underpowered sample size,&#xD;
      different methodology and short intervention periods are some factors raising the question of&#xD;
      effect size. Other trials have no control group. We are designing this study taking these&#xD;
      limitations into consideration. In addition we are using whole marine oil from the&#xD;
      zooplankton Calanus finmarchicus that has a high natural content of stearidonic acid 18:3 n-3&#xD;
      that is a precursor to EPA. The oil also has a high content of astaxanthines - a natural&#xD;
      antioxidant.&#xD;
&#xD;
      Earlier clinical studies have not used pure oil from zooplankton such as Calanus&#xD;
      finmarchicus. The oil is not processed chemically such as ethylation, that not only alter the&#xD;
      structure of the oil, but also devoid the product of its natural antioxidants.&#xD;
&#xD;
      Blood tests are taken before and after a 6 month intervention period. These blood tests&#xD;
      entail both omega-3 index analysis as well as general hematology and biochemistry.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 3, 2017</start_date>
  <completion_date type="Anticipated">July 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">July 31, 2024</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>ADHD rating scale by Russel Barkley</measure>
    <time_frame>0, 3, 6, and 12 months</time_frame>
    <description>Reduction in symptom score</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>BRIEF - Behavior Rating Inventory of Executive Function</measure>
    <time_frame>0, 3, 6, and 12 months</time_frame>
    <description>Reduction in symptom score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>SNAP-IV The Swanson Nolan and Pelham-IV Questionnaire</measure>
    <time_frame>0, 3, 6, and 12 months</time_frame>
    <description>Change</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ARI - Affective Reactivity Index - a scale that contains six symptom items and one impairment item about irritability</measure>
    <time_frame>0, 3, 6, and 12 months</time_frame>
    <description>Reduction in symptoms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TOVA CPT - Continuous Performance test - a task-oriented computerized assessment of attention-related problems in individuals aged 8 years and older</measure>
    <time_frame>0, 3, 6, and 12 months</time_frame>
    <description>Change</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>SDQ - Strength and Difficulty Questionnaire</measure>
    <time_frame>0, 3, 6, and 12 months</time_frame>
    <description>Psychological screening tool used to assess the behavioral and emotional strengths and difficulties of children and adolescents, consisting of 25 items across five dimensions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kid-Screen-52</measure>
    <time_frame>0, 3, 6, and 12 months</time_frame>
    <description>52 items examining Health-related Quality of Life</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">330</enrollment>
  <condition>ADHD</condition>
  <condition>ADD</condition>
  <arm_group>
    <arm_group_label>Calanus oil</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Children receiving omega-3 in form om calanus oil in capsule form</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Children receiving medical paraffin in capsule form (2 ml volume per day)</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Calanus oil</intervention_name>
    <description>Omega-3 oil in form of calanus oil</description>
    <arm_group_label>Calanus oil</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Medical Paraffin</intervention_name>
    <description>2ml per day</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - ADHD or ADD according to DSM-IV criteria&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  IQ below 70&#xD;
&#xD;
          -  infantil autism, psychosis, bipolar disorders and serious somatic disease&#xD;
&#xD;
          -  any abnormal or pathological blood test during trial&#xD;
&#xD;
          -  Omega-3 supplement taken until 3 months before inclusion&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>16 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Siv Kvernmo, MD PhD</last_name>
    <role>Study Director</role>
    <affiliation>University of Tromso</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Judeson R Joseph, MD</last_name>
    <phone>+4777755705</phone>
    <email>judeson.joseph@unn.no</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Siv E Kvernmo, MD PhD</last_name>
    <phone>+4777755726</phone>
    <email>siv.kvernmo@uit.no</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Finnmarkssykehuset SANKS BUP Karasjok</name>
      <address>
        <city>Karasjok</city>
        <state>Finnmark</state>
        <zip>9730</zip>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ingunn Eriksen</last_name>
      <phone>+4792281651</phone>
      <email>ingunn.eriksen@finnmarkssykehuset.no</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>University Hospital of North Norway</name>
      <address>
        <city>Tromsø</city>
        <state>Troms</state>
        <zip>9038</zip>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Judeson R Joseph, MD</last_name>
      <phone>77755705</phone>
      <email>judeson.joseph@unn.no</email>
    </contact>
    <contact_backup>
      <last_name>Siv Kvernmo, Prof MD</last_name>
      <phone>77755725</phone>
      <email>siv.kvernmo@uit.no</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Norway</country>
  </location_countries>
  <reference>
    <citation>Raine A, Portnoy J, Liu J, Mahoomed T, Hibbeln JR. Reduction in behavior problems with omega-3 supplementation in children aged 8-16 years: a randomized, double-blind, placebo-controlled, stratified, parallel-group trial. J Child Psychol Psychiatry. 2015 May;56(5):509-20. doi: 10.1111/jcpp.12314. Epub 2014 Aug 22.</citation>
    <PMID>25146492</PMID>
  </reference>
  <reference>
    <citation>Gow RV, Hibbeln JR, Parletta N. Current evidence and future directions for research with omega-3 fatty acids and attention deficit hyperactivity disorder. Curr Opin Clin Nutr Metab Care. 2015 Mar;18(2):133-8. doi: 10.1097/MCO.0000000000000140.</citation>
    <PMID>25581035</PMID>
  </reference>
  <reference>
    <citation>Heilskov Rytter MJ, Andersen LB, Houmann T, Bilenberg N, Hvolby A, Molgaard C, Michaelsen KF, Lauritzen L. Diet in the treatment of ADHD in children - a systematic review of the literature. Nord J Psychiatry. 2015 Jan;69(1):1-18. doi: 10.3109/08039488.2014.921933. Epub 2014 Jun 16.</citation>
    <PMID>24934907</PMID>
  </reference>
  <reference>
    <citation>Milte CM, Sinn N, Buckley JD, Coates AM, Young RM, Howe PR. Polyunsaturated fatty acids, cognition and literacy in children with ADHD with and without learning difficulties. J Child Health Care. 2011 Dec;15(4):299-311. doi: 10.1177/1367493511403953. Epub 2011 Aug 9.</citation>
    <PMID>21828168</PMID>
  </reference>
  <reference>
    <citation>Stonehouse W, Conlon CA, Podd J, Hill SR, Minihane AM, Haskell C, Kennedy D. DHA supplementation improved both memory and reaction time in healthy young adults: a randomized controlled trial. Am J Clin Nutr. 2013 May;97(5):1134-43. doi: 10.3945/ajcn.112.053371. Epub 2013 Mar 20.</citation>
    <PMID>23515006</PMID>
  </reference>
  <reference>
    <citation>Richardson AJ. Omega-3 fatty acids in ADHD and related neurodevelopmental disorders. Int Rev Psychiatry. 2006 Apr;18(2):155-72. doi: 10.1080/09540260600583031.</citation>
    <PMID>16777670</PMID>
  </reference>
  <reference>
    <citation>Montgomery P, Burton JR, Sewell RP, Spreckelsen TF, Richardson AJ. Low blood long chain omega-3 fatty acids in UK children are associated with poor cognitive performance and behavior: a cross-sectional analysis from the DOLAB study. PLoS One. 2013 Jun 24;8(6):e66697. doi: 10.1371/journal.pone.0066697. Print 2013. Erratum In: PLoS One. 2013;8(9). doi:10.1371/annotation/26c6b13f-b83a-4a3f-978a-c09d8ccf1ae2.</citation>
    <PMID>23826114</PMID>
  </reference>
  <reference>
    <citation>Hoper AC, Salma W, Sollie SJ, Hafstad AD, Lund J, Khalid AM, Raa J, Aasum E, Larsen TS. Wax esters from the marine copepod Calanus finmarchicus reduce diet-induced obesity and obesity-related metabolic disorders in mice. J Nutr. 2014 Feb;144(2):164-9. doi: 10.3945/jn.113.182501. Epub 2013 Nov 27.</citation>
    <PMID>24285691</PMID>
  </reference>
  <reference>
    <citation>Eilertsen KE, Maehre HK, Jensen IJ, Devold H, Olsen JO, Lie RK, Brox J, Berg V, Elvevoll EO, Osterud B. A wax ester and astaxanthin-rich extract from the marine copepod Calanus finmarchicus attenuates atherogenesis in female apolipoprotein E-deficient mice. J Nutr. 2012 Mar;142(3):508-12. doi: 10.3945/jn.111.145698. Epub 2012 Feb 8.</citation>
    <PMID>22323762</PMID>
  </reference>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>January 8, 2016</study_first_submitted>
  <study_first_submitted_qc>December 5, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 8, 2016</study_first_posted>
  <last_update_submitted>July 31, 2023</last_update_submitted>
  <last_update_submitted_qc>July 31, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ADHD</keyword>
  <keyword>omega 3</keyword>
  <keyword>children</keyword>
  <keyword>nutrition</keyword>
  <keyword>MUFA</keyword>
  <keyword>ADD</keyword>
  <keyword>PUFA</keyword>
  <keyword>Calanus</keyword>
  <keyword>learning difficulties</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Attention Deficit Disorder with Hyperactivity</mesh_term>
  </condition_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/NCT02986672
org study id: ADHD_Kvernmo
nct id: NCT02986672
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study aim to evaluate the effect of marine monounsaturated and polyunsaturated fatty
      acids on children aged from 6-16 years, with ADHD/ADD and related symptoms. The study is a
      randomized, double-blind placebo-control study including approximately 330 children from
      Norway. The primary outcome measure is ADHD core symptoms reported by caregivers, teachers
      and the child at 0 months (baseline), 6 months (end of treatment) and 12 months (6 months
      post treatment). The secondary outcome measures are reading and writing disabilities,
      cognitive functions, and physical Health.
Children with ADHD are shown to have low blood levels of omega-3 fatty acids, not related to
      diet. Low levels of omega-3 has also been directly related to poor cognition and behavior.
      Trials have shown that supplement with omega-3 may improve literacy and behavior in children
      with ADHD symptoms. It has also been shown to improve both memory and reaction time. The
      effect sizes found in meta analysis of placebo- controlled clinical trials on ADHD core
      symptoms are small to modest. In a study of adolescent mental health in North Norway in
      2003-2005 a significant association was found between intake of fish and hyperactivity as
      adolescents with a high intake showed less hyperactivity than peers with a low intake
      (unpublished results from The Norwegian Arctic Adolescent Health Study, Siv Kvernmo).

      There are several key limitations to the existing studies. Underpowered sample size,
      different methodology and short intervention periods are some factors raising the question of
      effect size. Other trials have no control group. We are designing this study taking these
      limitations into consideration. In addition we are using whole marine oil from the
      zooplankton Calanus finmarchicus that has a high natural content of stearidonic acid 18:3 n-3
      that is a precursor to EPA. The oil also has a high content of astaxanthines - a natural
      antioxidant.

      Earlier clinical studies have not used pure oil from zooplankton such as Calanus
      finmarchicus. The oil is not processed chemically such as ethylation, that not only alter the
      structure of the oil, but also devoid the product of its natural antioxidants.

      Blood tests are taken before and after a 6 month intervention period. These blood tests
      entail both omega-3 index analysis as well as general hematology and biochemistry.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: ADHD rating scale by Russel Barkley
time frame: 0, 3, 6, and 12 months
description: Reduction in symptom score
measure: BRIEF - Behavior Rating Inventory of Executive Function
time frame: 0, 3, 6, and 12 months
description: Reduction in symptom score
measure: SNAP-IV The Swanson Nolan and Pelham-IV Questionnaire
time frame: 0, 3, 6, and 12 months
description: Change
measure: ARI - Affective Reactivity Index - a scale that contains six symptom items and one impairment item about irritability
time frame: 0, 3, 6, and 12 months
description: Reduction in symptoms
measure: TOVA CPT - Continuous Performance test - a task-oriented computerized assessment of attention-related problems in individuals aged 8 years and older
time frame: 0, 3, 6, and 12 months
description: Change
measure: SDQ - Strength and Difficulty Questionnaire
time frame: 0, 3, 6, and 12 months
description: Psychological screening tool used to assess the behavioral and emotional strengths and difficulties of children and adolescents, consisting of 25 items across five dimensions
measure: Kid-Screen-52
time frame: 0, 3, 6, and 12 months
description: 52 items examining Health-related Quality of Life
arm group label: Calanus oil
arm group type: Active Comparator
description: Children receiving omega-3 in form om calanus oil in capsule form
arm group label: Placebo
arm group type: Placebo Comparator
description: Children receiving medical paraffin in capsule form (2 ml volume per day)
intervention type: Dietary Supplement
intervention name: Calanus oil
description: Omega-3 oil in form of calanus oil
arm group label: Calanus oil
intervention type: Other
intervention name: Medical Paraffin
description: 2ml per day
arm group label: Placebo
criteria: 
gender: All
minimum age: 6 Years
maximum age: 16 Years
healthy volunteers: No
last name: Siv Kvernmo, MD PhD
role: Study Director
affiliation: University of Tromso
last name: Judeson R Joseph, MD
phone: +4777755705
email: judeson.joseph@unn.no
last name: Siv E Kvernmo, MD PhD
phone: +4777755726
email: siv.kvernmo@uit.no
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
country: Norway
citation: Raine A, Portnoy J, Liu J, Mahoomed T, Hibbeln JR. Reduction in behavior problems with omega-3 supplementation in children aged 8-16 years: a randomized, double-blind, placebo-controlled, stratified, parallel-group trial. J Child Psychol Psychiatry. 2015 May;56(5):509-20. doi: 10.1111/jcpp.12314. Epub 2014 Aug 22.
PMID: 25146492
citation: Gow RV, Hibbeln JR, Parletta N. Current evidence and future directions for research with omega-3 fatty acids and attention deficit hyperactivity disorder. Curr Opin Clin Nutr Metab Care. 2015 Mar;18(2):133-8. doi: 10.1097/MCO.0000000000000140.
PMID: 25581035
citation: Heilskov Rytter MJ, Andersen LB, Houmann T, Bilenberg N, Hvolby A, Molgaard C, Michaelsen KF, Lauritzen L. Diet in the treatment of ADHD in children - a systematic review of the literature. Nord J Psychiatry. 2015 Jan;69(1):1-18. doi: 10.3109/08039488.2014.921933. Epub 2014 Jun 16.
PMID: 24934907
citation: Milte CM, Sinn N, Buckley JD, Coates AM, Young RM, Howe PR. Polyunsaturated fatty acids, cognition and literacy in children with ADHD with and without learning difficulties. J Child Health Care. 2011 Dec;15(4):299-311. doi: 10.1177/1367493511403953. Epub 2011 Aug 9.
PMID: 21828168
citation: Stonehouse W, Conlon CA, Podd J, Hill SR, Minihane AM, Haskell C, Kennedy D. DHA supplementation improved both memory and reaction time in healthy young adults: a randomized controlled trial. Am J Clin Nutr. 2013 May;97(5):1134-43. doi: 10.3945/ajcn.112.053371. Epub 2013 Mar 20.
PMID: 23515006
citation: Richardson AJ. Omega-3 fatty acids in ADHD and related neurodevelopmental disorders. Int Rev Psychiatry. 2006 Apr;18(2):155-72. doi: 10.1080/09540260600583031.
PMID: 16777670
citation: Montgomery P, Burton JR, Sewell RP, Spreckelsen TF, Richardson AJ. Low blood long chain omega-3 fatty acids in UK children are associated with poor cognitive performance and behavior: a cross-sectional analysis from the DOLAB study. PLoS One. 2013 Jun 24;8(6):e66697. doi: 10.1371/journal.pone.0066697. Print 2013. Erratum In: PLoS One. 2013;8(9). doi:10.1371/annotation/26c6b13f-b83a-4a3f-978a-c09d8ccf1ae2.
PMID: 23826114
citation: Hoper AC, Salma W, Sollie SJ, Hafstad AD, Lund J, Khalid AM, Raa J, Aasum E, Larsen TS. Wax esters from the marine copepod Calanus finmarchicus reduce diet-induced obesity and obesity-related metabolic disorders in mice. J Nutr. 2014 Feb;144(2):164-9. doi: 10.3945/jn.113.182501. Epub 2013 Nov 27.
PMID: 24285691
citation: Eilertsen KE, Maehre HK, Jensen IJ, Devold H, Olsen JO, Lie RK, Brox J, Berg V, Elvevoll EO, Osterud B. A wax ester and astaxanthin-rich extract from the marine copepod Calanus finmarchicus attenuates atherogenesis in female apolipoprotein E-deficient mice. J Nutr. 2012 Mar;142(3):508-12. doi: 10.3945/jn.111.145698. Epub 2012 Feb 8.
PMID: 22323762
responsible party type: Sponsor
mesh term: Attention Deficit Disorder with Hyperactivity
sharing ipd: No