<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/NCT02990091</url>
  </required_header>
  <id_info>
    <org_study_id>826109</org_study_id>
    <nct_id>NCT02990091</nct_id>
  </id_info>
  <brief_title>Derivatives of Omega-3 HUFA as Biomarkers of Traumatic Brain Injury</brief_title>
  <official_title>Traumatic Brain Injury Recovery With n-3 Highly Unsaturated Fatty Acids (HUFAs): A Biomarker-driven Approach</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pennsylvania</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute on Alcohol Abuse and Alcoholism (NIAAA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pennsylvania</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase 2 clinical trial designed to obtain data on relationships between potentially&#xD;
      therapeutic doses of n-3 HUFA (highly unsaturated fatty acids) and their bioactive molecular&#xD;
      derivatives, synaptamide, 17-hydroxy-DHA, and D-series resolvins, on clinical outcomes after&#xD;
      TBI.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Unable to recruit participants&#xD;
  </why_stopped>
  <start_date>January 2017</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">January 2023</primary_completion_date>
  <phase>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>Diagnostic</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Relationship of varying doses of n-3 HUFAs on blood levels of the following bioactive metabolites</measure>
    <time_frame>14 days consecutively</time_frame>
    <description>Bioactive metabolites being looked at are: synaptamide (n-docosahexaenoylethanolamine), 17-hydroxy-DHA, and D-series resolvins and determine relationship of n-3 HUFAs on blood levels of indicators of neuroinflammatory damage including Brain Derived Neurotrophic Factor (BDNF) in humans over 14 days after TBI.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Relationship of n-3 HUFA blood levels and clinical outcomes measured by the Glasgow Outcome Scale-Extended (GOSE)</measure>
    <time_frame>14 days consecutively</time_frame>
    <description>Clinical outcomes will include functional outcomes and will be assessed by using the TBI Common Data Elements Outcome battery. The analysis will focus on the Glasgow Outcome Scale-Extended (GOS-E) an ordinal scale based on a structured questionnaire which is universally used in TBI clinical studies.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evalute potential adverse events</measure>
    <time_frame>14 days consecutively</time_frame>
    <description>Evaluate potential adverse side effects including gastrointestinal tolerance and adverse neurological outcomes.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>TBI</condition>
  <arm_group>
    <arm_group_label>1,000mg/day n-3 HUFA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will take one capsule daily starting at study enrollment (within 24 hours of injury) for 14 consecutive days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>4,000 mg/day n-3 HUFA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will take 2 capsules twice daily starting at enrollment (within 24 hours of injury) for 14 consecutive days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>1 capsule safflower seed oil</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects will take 1 capsule daily starting at enrollment (within 24 hours of injury) for 14 consecutive days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>4 capsules safflower seed oil</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects will take 2 capsules twice daily starting at enrollment (within 24 hours of injury) for 14 consecutive days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Omega 3 fatty acid</intervention_name>
    <description>LOVAZA is an FDA approved drug that is lawfully marketed in the United States by GlaxoSmithKline. There is no intent to use the results of this study to support a change in the labeling or the advertising of the drug. The highest dose administered for the study is the recommended prescribed dose of LOVAZA, therefore not creating greater risk. The patient population and route of administration will not significantly increase the risk associated with the use of the product. We will be using this drug under an IND exemption.</description>
    <arm_group_label>1,000mg/day n-3 HUFA</arm_group_label>
    <arm_group_label>4,000 mg/day n-3 HUFA</arm_group_label>
    <other_name>LOVAZA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Safflower seed oil</intervention_name>
    <description>Safflower seed oil is a commonly used dietary supplement. It has been chosen to be used as a comparative to the LOVAZA because of its non-omega-3 fats. There will be no increased risk due to dosage, route of administration, or patient population.</description>
    <arm_group_label>1 capsule safflower seed oil</arm_group_label>
    <arm_group_label>4 capsules safflower seed oil</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 18-55&#xD;
&#xD;
          2. Documented/ verified TBI&#xD;
&#xD;
          3. Ability to swallow study agent within 48h of injury&#xD;
&#xD;
          4. If a sexually active female who is able to get pregnant, must be already taking birth&#xD;
             control (prescription contraception)&#xD;
&#xD;
          5. Visual acuity/ hearing adequate for testing&#xD;
&#xD;
          6. Fluency in English or Spanish&#xD;
&#xD;
          7. Ability to provide informed consent for themselves&#xD;
&#xD;
          8. Co-enrolled in PARC-TBI protocol (IRB protocol #825783) or TRACK-TBI (IRB protocol&#xD;
             #825503)&#xD;
&#xD;
          9. GCS 13-15&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Unstable respiratory or hemodynamic status&#xD;
&#xD;
          2. Evidence of penetrating brain injury&#xD;
&#xD;
          3. Requirement for craniotomy or craniectomy&#xD;
&#xD;
          4. Evidence of serious infectious complications&#xD;
&#xD;
          5. Acute ischemic heart disease or abnormal heart rhythm&#xD;
&#xD;
          6. History of abnormality in liver function&#xD;
&#xD;
          7. History or evidence of active malignancy&#xD;
&#xD;
          8. History of diabetes&#xD;
&#xD;
          9. History of pre-existing neurologic disorder, such as dementia, uncontrolled epilepsy,&#xD;
             multiple sclerosis, strokes, brain tumors, prior severe TBI, or other disorder that&#xD;
             confounds interpretation neuropsychological results&#xD;
&#xD;
         10. History of pre-existing disabling Axis I psychiatric disorder, such as major&#xD;
             depression, schizophrenia, bipolar disorder or dementia&#xD;
&#xD;
         11. Allergy to omega-3 fatty acid ethyl esters or any ingredient of the study agent.&#xD;
&#xD;
         12. Known allergy to Safflower seed oil or ragweed plants&#xD;
&#xD;
         13. Consumption of fish or seafood 3 or more times per week on average or regular&#xD;
             administration of omega-3 supplements (e.g., cod liver oil, borage oil, fish oil or&#xD;
             evening primrose oil) defined as an average of 250 mg/day of n-3 HUFAs, over the&#xD;
             previous 3 months.&#xD;
&#xD;
         14. Pregnancy or breast-feeding&#xD;
&#xD;
         15. Prisoners or patients in custody&#xD;
&#xD;
         16. Allergy, hypersensitivity, or intolerance to fish oils or omega-3 fats which are found&#xD;
             in fish.&#xD;
&#xD;
         17. Use of anticoagulant medications or aspirin more than once per week within the last&#xD;
             three months&#xD;
&#xD;
         18. Enrollment in any concurrent research protocols that would interfere with participant&#xD;
             safety or research data integrity.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ramon Diaz-Arrastia, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pennsylvania</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Penn Presbyterian Medical Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>December 5, 2016</study_first_submitted>
  <study_first_submitted_qc>December 7, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 12, 2016</study_first_posted>
  <last_update_submitted>October 10, 2022</last_update_submitted>
  <last_update_submitted_qc>October 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 13, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Pennsylvania</investigator_affiliation>
    <investigator_full_name>Ramon Diaz-Arrastia</investigator_full_name>
    <investigator_title>Presidential Professor</investigator_title>
  </responsible_party>
  <keyword>TBI</keyword>
  <keyword>DHA</keyword>
  <keyword>omega-3 highly unsaturated fatty acids</keyword>
  <keyword>synaptamide</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Injuries</mesh_term>
    <mesh_term>Brain Injuries, Traumatic</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/NCT02990091
org study id: 826109
nct id: NCT02990091
lead sponsor: 
collaborator: 
has dmc: No
This is a Phase 2 clinical trial designed to obtain data on relationships between potentially
      therapeutic doses of n-3 HUFA (highly unsaturated fatty acids) and their bioactive molecular
      derivatives, synaptamide, 17-hydroxy-DHA, and D-series resolvins, on clinical outcomes after
      TBI.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: Single (Participant)
measure: Relationship of varying doses of n-3 HUFAs on blood levels of the following bioactive metabolites
time frame: 14 days consecutively
description: Bioactive metabolites being looked at are: synaptamide (n-docosahexaenoylethanolamine), 17-hydroxy-DHA, and D-series resolvins and determine relationship of n-3 HUFAs on blood levels of indicators of neuroinflammatory damage including Brain Derived Neurotrophic Factor (BDNF) in humans over 14 days after TBI.
measure: Relationship of n-3 HUFA blood levels and clinical outcomes measured by the Glasgow Outcome Scale-Extended (GOSE)
time frame: 14 days consecutively
description: Clinical outcomes will include functional outcomes and will be assessed by using the TBI Common Data Elements Outcome battery. The analysis will focus on the Glasgow Outcome Scale-Extended (GOS-E) an ordinal scale based on a structured questionnaire which is universally used in TBI clinical studies.
measure: Evalute potential adverse events
time frame: 14 days consecutively
description: Evaluate potential adverse side effects including gastrointestinal tolerance and adverse neurological outcomes.
arm group label: 1,000mg/day n-3 HUFA
arm group type: Experimental
description: Subjects will take one capsule daily starting at study enrollment (within 24 hours of injury) for 14 consecutive days.
arm group label: 4,000 mg/day n-3 HUFA
arm group type: Experimental
description: Subjects will take 2 capsules twice daily starting at enrollment (within 24 hours of injury) for 14 consecutive days.
arm group label: 1 capsule safflower seed oil
arm group type: Placebo Comparator
description: Subjects will take 1 capsule daily starting at enrollment (within 24 hours of injury) for 14 consecutive days.
arm group label: 4 capsules safflower seed oil
arm group type: Placebo Comparator
description: Subjects will take 2 capsules twice daily starting at enrollment (within 24 hours of injury) for 14 consecutive days.
intervention type: Drug
intervention name: Omega 3 fatty acid
description: LOVAZA is an FDA approved drug that is lawfully marketed in the United States by GlaxoSmithKline. There is no intent to use the results of this study to support a change in the labeling or the advertising of the drug. The highest dose administered for the study is the recommended prescribed dose of LOVAZA, therefore not creating greater risk. The patient population and route of administration will not significantly increase the risk associated with the use of the product. We will be using this drug under an IND exemption.
arm group label: 1,000mg/day n-3 HUFA
arm group label: 4,000 mg/day n-3 HUFA
other name: LOVAZA
intervention type: Dietary Supplement
intervention name: Safflower seed oil
description: Safflower seed oil is a commonly used dietary supplement. It has been chosen to be used as a comparative to the LOVAZA because of its non-omega-3 fats. There will be no increased risk due to dosage, route of administration, or patient population.
arm group label: 1 capsule safflower seed oil
arm group label: 4 capsules safflower seed oil
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
last name: Ramon Diaz-Arrastia, MD, PhD
role: Principal Investigator
affiliation: University of Pennsylvania
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Pennsylvania
investigator full name: Ramon Diaz-Arrastia
investigator title: Presidential Professor
mesh term: Brain Injuries
mesh term: Brain Injuries, Traumatic
sharing ipd: No