<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/NCT03295708</url>
  </required_header>
  <id_info>
    <org_study_id>MDD201610</org_study_id>
    <nct_id>NCT03295708</nct_id>
  </id_info>
  <brief_title>Fish Oil as Adjunct Treatment for Major Depressive Disorder</brief_title>
  <official_title>Safety, Effectiveness, and Mechanism of Fish Oil as Adjunct Treatment for Major Depressive Disorder - a 12-month Randomized, Placebo Controlled Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Second Xiangya Hospital of Central South University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Xiangya Hospital of Central South University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Second Xiangya Hospital of Central South University</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this proposed study, the investigators will evaluate the effects of fish oil add-on in&#xD;
      treatment of major depressive disorder(MDD).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Participants are randomly assigned to two groups (n=60): control (placebo, soybean) and fish&#xD;
      oil (containing EPA 1440mg, DHA 960mg). The experimental groups will be compared to placebo&#xD;
      to evaluate if it may benefit clinical symptoms, cognitive symptoms and metabolic markers in&#xD;
      MDD patients. We also plan to investigate the changes in markers of inflammation at the same&#xD;
      time.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">October 1, 2017</start_date>
  <completion_date type="Anticipated">April 1, 2020</completion_date>
  <primary_completion_date type="Anticipated">October 1, 2019</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in Hamilton Depression Scale (HAMD) HAMD</measure>
    <time_frame>W0 W4 W12 W24 W48</time_frame>
    <description>Subjects were evaluated for current depression with HAMD.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in Clinical Global Impression (CGI)</measure>
    <time_frame>W0 W4 W12 W24 W48</time_frame>
    <description>Subjects were evaluated for current severity of disease with CGI.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Hamilton Anxiety Scale (HAMA)</measure>
    <time_frame>W0 W4 W12 W24 W48</time_frame>
    <description>Subjects were evaluated for current anxiety with HAMA.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Beck Depression Rating Scale (BDI)</measure>
    <time_frame>W0 W4 W12 W24 W48</time_frame>
    <description>The BDI is a self-report inventory of depression symptom.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Self-Rating Anxiety Scale (SAS)</measure>
    <time_frame>W0 W4 W12 W24 W48</time_frame>
    <description>The SAS is a self-report inventory of anxiety symptom.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Major Depressive Disorder</condition>
  <arm_group>
    <arm_group_label>experimental group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>the experimental group will be given 4 fish oil capsules (1g/one capsule)twice daily after two meals at roughly the same time each day,lasting for the first 6 months.fish oil capsule will be provided by the Hunan Kangqi100 Biological Technology Co.Ltd.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>control group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>the control group will be given 4 soybean oil capsules ( placebo capsule,1g/one capsule) twice daily after two meals at roughly the same time each day,lasting for the first 6 months.placebo capsule will be provided by the Hunan Kangqi100 Biological Technology Co.Ltd.The placebo capsule's appearance and flavor are made the exactly the same as the fish oil capsules .</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>fish oil capsule</intervention_name>
    <description>N-3 PUFAs is a kind of essential fatty acid,however the formation is too slow. Studies show that intakes of N-3 PUFAs is associated with MDD.It have to be got from food like deep-sea fishes. EPA and DHA are crucial for the body.Although studies have shown that reduced N-3 PUFAs were correlated with MDD, and patients with an elevated rate of N-6 PUFAs /N-3 PUFAs or a low level of DHA may be at higher odds for suicide. Trials on whether N-3 PUFAs is effective in the treatment of MDD is still controversial, which might be affected by several factors, such as dose, duration etc.. Now there is no large-scale randomized controlled clinical trial in determining the effects of N-3 PUFAs add-on in treatment of MDD.</description>
    <arm_group_label>experimental group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>soybean oil capsule</intervention_name>
    <description>placebo capsule</description>
    <arm_group_label>control group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Able to provide informed consent&#xD;
&#xD;
          2. Men or women aged 18-50 years&#xD;
&#xD;
          3. A primary psychiatric diagnosis of major depressive disorder (MDD), by Diagnostic and&#xD;
             Statistical Manual-5th ed (DSM-5) using the MINI&#xD;
&#xD;
          4. HAMD total score≥21&#xD;
&#xD;
          5. No significantly modification of their diet from the time they sign consent to the end&#xD;
             of study participation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Suffering from other serious somatic diseases or comorbidities&#xD;
&#xD;
          2. Patients with serious nervous system disease&#xD;
&#xD;
          3. Patients in accordance with diagnostic standards of other mental illness&#xD;
&#xD;
          4. Patients who need to take benzodiazepine every day, and who currently need to be&#xD;
             treated by electroconvulsive therapy or have received electroconvulsive therapy in the&#xD;
             past 6 months&#xD;
&#xD;
          5. Pregnant women or lactating women, women with pregnancy plans during the trial period&#xD;
             (12 months), women with a high risk of pregnancy but without taking any contraceptive&#xD;
             measures&#xD;
&#xD;
          6. Patients with apparent suicide attempt or suicidal behavior&#xD;
&#xD;
          7. Any condition or medicines that may have an effect on biomarkers (within 1 week of the&#xD;
             screening period or during whole trial period): long-term, regular use of NSAIDs,&#xD;
             COX-2 inhibitors, immunosuppressant, steroids, interferon, chemotherapeutics,&#xD;
             anticoagulants, malignancy, active autoimmune diseases, inflammatory bowel diseases,&#xD;
             etc&#xD;
&#xD;
          8. Allergy history of PUFA&#xD;
&#xD;
          9. Intake of Fish oil more than 3g per day or eat fatty fish more than 3 times a week&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jindong Chen, MD</last_name>
    <role>Study Director</role>
    <affiliation>Central South University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Lu Wang, MD</last_name>
    <phone>+8615116331768</phone>
    <email>luwang112@163.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Mimi Tang, MD</last_name>
    <phone>+8615802607545</phone>
    <email>tangmimi1989@163.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Mental Health Institute, Second Xiangya Hospital of Central South University</name>
      <address>
        <city>Changsha</city>
        <state>Hunan</state>
        <zip>410000</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lu Wang, M.D.</last_name>
      <phone>+8615116331768</phone>
      <email>luwang112@163.com</email>
    </contact>
    <contact_backup>
      <last_name>Mi Mi Tang, M.D.</last_name>
      <phone>+8617136372000</phone>
      <email>tangmimi1989@163.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Kessler RC, Birnbaum H, Bromet E, Hwang I, Sampson N, Shahly V. Age differences in major depression: results from the National Comorbidity Survey Replication (NCS-R). Psychol Med. 2010 Feb;40(2):225-37. doi: 10.1017/S0033291709990213. Epub 2009 Jun 17.</citation>
    <PMID>19531277</PMID>
  </reference>
  <reference>
    <citation>Monroe SM, Harkness KL. Recurrence in major depression: a conceptual analysis. Psychol Rev. 2011 Oct;118(4):655-74. doi: 10.1037/a0025190. Erratum In: Psychol Rev. 2011 Oct;118(4):674.</citation>
    <PMID>21895384</PMID>
  </reference>
  <reference>
    <citation>Appleton KM, Rogers PJ, Ness AR. Updated systematic review and meta-analysis of the effects of n-3 long-chain polyunsaturated fatty acids on depressed mood. Am J Clin Nutr. 2010 Mar;91(3):757-70. doi: 10.3945/ajcn.2009.28313. Epub 2010 Feb 3.</citation>
    <PMID>20130098</PMID>
  </reference>
  <reference>
    <citation>McNamara RK, Carlson SE. Role of omega-3 fatty acids in brain development and function: potential implications for the pathogenesis and prevention of psychopathology. Prostaglandins Leukot Essent Fatty Acids. 2006 Oct-Nov;75(4-5):329-49. doi: 10.1016/j.plefa.2006.07.010. Epub 2006 Sep 1.</citation>
    <PMID>16949263</PMID>
  </reference>
  <reference>
    <citation>Freeman MP, Rapaport MH. Omega-3 fatty acids and depression: from cellular mechanisms to clinical care. J Clin Psychiatry. 2011 Feb;72(2):258-9. doi: 10.4088/JCP.11ac06830. No abstract available.</citation>
    <PMID>21382308</PMID>
  </reference>
  <reference>
    <citation>Bloch MH, Hannestad J. Omega-3 fatty acids for the treatment of depression: systematic review and meta-analysis. Mol Psychiatry. 2012 Dec;17(12):1272-82. doi: 10.1038/mp.2011.100. Epub 2011 Sep 20.</citation>
    <PMID>21931319</PMID>
  </reference>
  <reference>
    <citation>Sprecher H. Metabolism of highly unsaturated n-3 and n-6 fatty acids. Biochim Biophys Acta. 2000 Jul 19;1486(2-3):219-31. doi: 10.1016/s1388-1981(00)00077-9. No abstract available.</citation>
    <PMID>10903473</PMID>
  </reference>
  <reference>
    <citation>Xie L, Innis SM. Association of fatty acid desaturase gene polymorphisms with blood lipid essential fatty acids and perinatal depression among Canadian women: a pilot study. J Nutrigenet Nutrigenomics. 2009;2(4-5):243-50. doi: 10.1159/000255636. Epub 2010 Apr 15.</citation>
    <PMID>20395685</PMID>
  </reference>
  <reference>
    <citation>Lalovic A, Klempan T, Sequeira A, Luheshi G, Turecki G. Altered expression of lipid metabolism and immune response genes in the frontal cortex of suicide completers. J Affect Disord. 2010 Jan;120(1-3):24-31. doi: 10.1016/j.jad.2009.04.007.</citation>
    <PMID>19443042</PMID>
  </reference>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>September 18, 2017</study_first_submitted>
  <study_first_submitted_qc>September 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 28, 2017</study_first_posted>
  <last_update_submitted>October 6, 2017</last_update_submitted>
  <last_update_submitted_qc>October 6, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 10, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Second Xiangya Hospital of Central South University</investigator_affiliation>
    <investigator_full_name>Jin-Dong Chen</investigator_full_name>
    <investigator_title>Director of Mental Health Institute of the Second Xiangya Hospital</investigator_title>
  </responsible_party>
  <keyword>Major depressive disorder,Fish Oil</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>June 1,2020, Email to Dr. Chen Jindong(chenjd269@163.com)</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 9, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/08/NCT03295708/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03295708
org study id: MDD201610
nct id: NCT03295708
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
In this proposed study, the investigators will evaluate the effects of fish oil add-on in
      treatment of major depressive disorder(MDD).
Participants are randomly assigned to two groups (n=60): control (placebo, soybean) and fish
      oil (containing EPA 1440mg, DHA 960mg). The experimental groups will be compared to placebo
      to evaluate if it may benefit clinical symptoms, cognitive symptoms and metabolic markers in
      MDD patients. We also plan to investigate the changes in markers of inflammation at the same
      time.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Changes in Hamilton Depression Scale (HAMD) HAMD
time frame: W0 W4 W12 W24 W48
description: Subjects were evaluated for current depression with HAMD.
measure: Changes in Clinical Global Impression (CGI)
time frame: W0 W4 W12 W24 W48
description: Subjects were evaluated for current severity of disease with CGI.
measure: Changes in Hamilton Anxiety Scale (HAMA)
time frame: W0 W4 W12 W24 W48
description: Subjects were evaluated for current anxiety with HAMA.
measure: Changes in Beck Depression Rating Scale (BDI)
time frame: W0 W4 W12 W24 W48
description: The BDI is a self-report inventory of depression symptom.
measure: Changes in Self-Rating Anxiety Scale (SAS)
time frame: W0 W4 W12 W24 W48
description: The SAS is a self-report inventory of anxiety symptom.
arm group label: experimental group
arm group type: Experimental
description: the experimental group will be given 4 fish oil capsules (1g/one capsule)twice daily after two meals at roughly the same time each day,lasting for the first 6 months.fish oil capsule will be provided by the Hunan Kangqi100 Biological Technology Co.Ltd.
arm group label: control group
arm group type: Placebo Comparator
description: the control group will be given 4 soybean oil capsules ( placebo capsule,1g/one capsule) twice daily after two meals at roughly the same time each day,lasting for the first 6 months.placebo capsule will be provided by the Hunan Kangqi100 Biological Technology Co.Ltd.The placebo capsule's appearance and flavor are made the exactly the same as the fish oil capsules .
intervention type: Dietary Supplement
intervention name: fish oil capsule
description: N-3 PUFAs is a kind of essential fatty acid,however the formation is too slow. Studies show that intakes of N-3 PUFAs is associated with MDD.It have to be got from food like deep-sea fishes. EPA and DHA are crucial for the body.Although studies have shown that reduced N-3 PUFAs were correlated with MDD, and patients with an elevated rate of N-6 PUFAs /N-3 PUFAs or a low level of DHA may be at higher odds for suicide. Trials on whether N-3 PUFAs is effective in the treatment of MDD is still controversial, which might be affected by several factors, such as dose, duration etc.. Now there is no large-scale randomized controlled clinical trial in determining the effects of N-3 PUFAs add-on in treatment of MDD.
arm group label: experimental group
intervention type: Dietary Supplement
intervention name: soybean oil capsule
description: placebo capsule
arm group label: control group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: No
last name: Jindong Chen, MD
role: Study Director
affiliation: Central South University
last name: Lu Wang, MD
phone: +8615116331768
email: luwang112@163.com
last name: Mimi Tang, MD
phone: +8615802607545
email: tangmimi1989@163.com
facility: 
status: Recruiting
contact: 
contact backup: 
country: China
citation: Kessler RC, Birnbaum H, Bromet E, Hwang I, Sampson N, Shahly V. Age differences in major depression: results from the National Comorbidity Survey Replication (NCS-R). Psychol Med. 2010 Feb;40(2):225-37. doi: 10.1017/S0033291709990213. Epub 2009 Jun 17.
PMID: 19531277
citation: Monroe SM, Harkness KL. Recurrence in major depression: a conceptual analysis. Psychol Rev. 2011 Oct;118(4):655-74. doi: 10.1037/a0025190. Erratum In: Psychol Rev. 2011 Oct;118(4):674.
PMID: 21895384
citation: Appleton KM, Rogers PJ, Ness AR. Updated systematic review and meta-analysis of the effects of n-3 long-chain polyunsaturated fatty acids on depressed mood. Am J Clin Nutr. 2010 Mar;91(3):757-70. doi: 10.3945/ajcn.2009.28313. Epub 2010 Feb 3.
PMID: 20130098
citation: McNamara RK, Carlson SE. Role of omega-3 fatty acids in brain development and function: potential implications for the pathogenesis and prevention of psychopathology. Prostaglandins Leukot Essent Fatty Acids. 2006 Oct-Nov;75(4-5):329-49. doi: 10.1016/j.plefa.2006.07.010. Epub 2006 Sep 1.
PMID: 16949263
citation: Freeman MP, Rapaport MH. Omega-3 fatty acids and depression: from cellular mechanisms to clinical care. J Clin Psychiatry. 2011 Feb;72(2):258-9. doi: 10.4088/JCP.11ac06830. No abstract available.
PMID: 21382308
citation: Bloch MH, Hannestad J. Omega-3 fatty acids for the treatment of depression: systematic review and meta-analysis. Mol Psychiatry. 2012 Dec;17(12):1272-82. doi: 10.1038/mp.2011.100. Epub 2011 Sep 20.
PMID: 21931319
citation: Sprecher H. Metabolism of highly unsaturated n-3 and n-6 fatty acids. Biochim Biophys Acta. 2000 Jul 19;1486(2-3):219-31. doi: 10.1016/s1388-1981(00)00077-9. No abstract available.
PMID: 10903473
citation: Xie L, Innis SM. Association of fatty acid desaturase gene polymorphisms with blood lipid essential fatty acids and perinatal depression among Canadian women: a pilot study. J Nutrigenet Nutrigenomics. 2009;2(4-5):243-50. doi: 10.1159/000255636. Epub 2010 Apr 15.
PMID: 20395685
citation: Lalovic A, Klempan T, Sequeira A, Luheshi G, Turecki G. Altered expression of lipid metabolism and immune response genes in the frontal cortex of suicide completers. J Affect Disord. 2010 Jan;120(1-3):24-31. doi: 10.1016/j.jad.2009.04.007.
PMID: 19443042
responsible party type: Principal Investigator
investigator affiliation: Second Xiangya Hospital of Central South University
investigator full name: Jin-Dong Chen
investigator title: Director of Mental Health Institute of the Second Xiangya Hospital
mesh term: Depressive Disorder
mesh term: Depression
mesh term: Depressive Disorder, Major
sharing ipd: Undecided
ipd description: June 1,2020, Email to Dr. Chen Jindong(chenjd269@163.com)
provided document: 