<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/NCT03277586</url>
  </required_header>
  <id_info>
    <org_study_id>6020656</org_study_id>
    <nct_id>NCT03277586</nct_id>
  </id_info>
  <brief_title>Effects of Probiotics on Symptoms of Depression</brief_title>
  <acronym>EPSD</acronym>
  <official_title>Effects of Probiotics on Symptoms of Depression</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Queen's University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Queen's University</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Preclinical and clinical studies have shown that consuming probiotics can improve mood,&#xD;
      anxiety, and cognition, as well as alter brain activity in both rodents and healthy humans.&#xD;
      Data from our recent open-label, 8-week pilot study provided the first evidence of these&#xD;
      effects in depressed patients, with significant improvements observed in overall mood,&#xD;
      anhedonia, and sleep quality. To further support this evidence and expand upon the search for&#xD;
      biomarkers in depression, data from this pilot study is being used to plan a 16-week,&#xD;
      double-blind randomized placebo-controlled trial to assess the effects of probiotics on&#xD;
      depression. Participants diagnosed with depression recruited from the greater Kingston area&#xD;
      will orally consume a probiotic supplement containing Lactobacillus helveticus and&#xD;
      Bifidobacterium longum (Probio'Stick, Lallemand Health Solutions) or placebo once daily.&#xD;
      Participants will undergo clinical assessments measuring mood, anxiety, cognition, and sleep&#xD;
      using a battery of validated clinical scales to assess efficacy of the probiotic alleviating&#xD;
      depressive symptoms; sleep will also be assessed objectively with an ambulatory&#xD;
      polysomnogram. Neuroimaging data will be collected using magnetic resonance imaging and&#xD;
      electroencephalography to look at functional, structural, and electrical changes in the brain&#xD;
      associated with consumption of the probiotic. Molecular data will be collected from blood,&#xD;
      stool, and urine samples to look at levels of cytokines and serotonin, and explore potential&#xD;
      genes and proteins that may predict outcomes in depression. An informatics-based approach&#xD;
      will be used to integrate clinical, neuroimaging, and molecular data to look for biomarkers&#xD;
      that indicate disease state and predict antidepressant-like response to the probiotic.&#xD;
      Results: We expect results to replicate and expand on our pilot data, demonstrating that&#xD;
      probiotics are effective in alleviating symptoms of depression, and to find biomarkers that&#xD;
      will predict these outcomes. The findings from this study will contribute robust scientific&#xD;
      data that is currently lacking in this emerging field.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    COVID-19&#xD;
  </why_stopped>
  <start_date type="Actual">May 29, 2018</start_date>
  <completion_date type="Actual">November 30, 2020</completion_date>
  <primary_completion_date type="Actual">November 30, 2020</primary_completion_date>
  <phase>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>16-week Double-blind randomized placebo-controlled dual-phase trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mood</measure>
    <time_frame>16 weeks</time_frame>
    <description>Montgomery-Asberg Depression Rating Scale</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Anxiety</measure>
    <time_frame>16 weeks</time_frame>
    <description>Generalized Anxiety Disorder 7-item Scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anhedonia</measure>
    <time_frame>16 weeks</time_frame>
    <description>Snaith Hamilton Pleasure Scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognition</measure>
    <time_frame>16 weeks</time_frame>
    <description>CNS Vital Signs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokines</measure>
    <time_frame>16 weeks</time_frame>
    <description>Blood plasma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serotonin</measure>
    <time_frame>16 weeks</time_frame>
    <description>Blood Plasma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Microbiome</measure>
    <time_frame>16 weeks</time_frame>
    <description>Stool</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Brain structure/function</measure>
    <time_frame>8 weeks</time_frame>
    <description>fMRI</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Depression</condition>
  <condition>Anxiety</condition>
  <arm_group>
    <arm_group_label>Probio'Stick</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Probio'Stick</intervention_name>
    <description>Probiotic supplement containing Lactobacillus helveticus and Bifidobacterium longum</description>
    <arm_group_label>Probio'Stick</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Identically formulated and packaged inactive substance</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Diagnosis of Major Depressive Disorder (MDD) according to DSM-5 as determined by MINI&#xD;
&#xD;
          2. Current depressive episode with a MADRS score of 20&#xD;
&#xD;
          3. Males and females between ages 18 and 65&#xD;
&#xD;
          4. Able to understand and comply with the requirements of the study&#xD;
&#xD;
          5. Provision of written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Current use of any antidepressant drug&#xD;
&#xD;
          2. Three or more previous episodes of depression&#xD;
&#xD;
          3. Failure to respond to another treatment in the current episode&#xD;
&#xD;
          4. Use of any antibiotic drug in the past 4 weeks (may be eligible to participate after a&#xD;
             1-month washout period). Should a participant require an antibiotic drug during the 16&#xD;
             week study period, they may continue with the study but must take the probiotic 4-6&#xD;
             hours before or after they take the antibiotic.&#xD;
&#xD;
          5. Use of any sleep medication in the past 4 weeks (may be eligible to participate after&#xD;
             a 1-month washout period)&#xD;
&#xD;
          6. Milk, yeast, or soy allergy&#xD;
&#xD;
          7. History of alcohol or substance dependence in the past 6 months&#xD;
&#xD;
          8. Use of probiotic product in the past 2 weeks (may be eligible to participate after a&#xD;
             2-week washout period) and during the trial&#xD;
&#xD;
          9. Use of any type of laxative&#xD;
&#xD;
         10. Consumption of products fortified in probiotics 2 weeks before and during the trial&#xD;
&#xD;
         11. High risk of suicide (score 4 or more on item 10 of MADRS)&#xD;
&#xD;
         12. Psychotic symptoms determined by the MINI&#xD;
&#xD;
         13. Bipolar Disorder determined by the MINI&#xD;
&#xD;
         14. Women who are pregnant, breastfeeding, or planning to become pregnant during the&#xD;
             course of the trial (determined by a pregnancy test performed at the screening visit&#xD;
             and confirmation of the use of appropriate contraception)&#xD;
&#xD;
         15. Immunodeficiency (immuno-compromised and immuno-suppressed participants; e.g. AIDS,&#xD;
             lymphoma, participants undergoing long-term corticosteroid treatment, chemotherapy and&#xD;
             allograft participants)&#xD;
&#xD;
         16. Unstable or severe medical conditions (e.g. cancer, cardiovascular, renal, lung,&#xD;
             diabetes, psychiatric illness, bleeding disorders, etc.)&#xD;
&#xD;
         17. The use of natural health products (NHPs; e.g. St. John's Wort, melatonin, passion&#xD;
             flower, etc.) that affect depression or sleep is not allowed in the trial&#xD;
&#xD;
         18. Electroconvulsive therapy (ECT) in the year prior to participation in the study&#xD;
&#xD;
         19. Taking medication or other not-permitted treatment that cannot be safely discontinued&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Providence Care Hospital</name>
      <address>
        <city>Kingston</city>
        <state>Ontario</state>
        <zip>K7L 4X3</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>September 1, 2017</study_first_submitted>
  <study_first_submitted_qc>September 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 11, 2017</study_first_posted>
  <last_update_submitted>January 13, 2021</last_update_submitted>
  <last_update_submitted_qc>January 13, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 15, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Queen's University</investigator_affiliation>
    <investigator_full_name>Dr. Roumen Milev</investigator_full_name>
    <investigator_title>Head, Department of Psychiatry</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder</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/NCT03277586
org study id: 6020656
nct id: NCT03277586
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Preclinical and clinical studies have shown that consuming probiotics can improve mood,
      anxiety, and cognition, as well as alter brain activity in both rodents and healthy humans.
      Data from our recent open-label, 8-week pilot study provided the first evidence of these
      effects in depressed patients, with significant improvements observed in overall mood,
      anhedonia, and sleep quality. To further support this evidence and expand upon the search for
      biomarkers in depression, data from this pilot study is being used to plan a 16-week,
      double-blind randomized placebo-controlled trial to assess the effects of probiotics on
      depression. Participants diagnosed with depression recruited from the greater Kingston area
      will orally consume a probiotic supplement containing Lactobacillus helveticus and
      Bifidobacterium longum (Probio'Stick, Lallemand Health Solutions) or placebo once daily.
      Participants will undergo clinical assessments measuring mood, anxiety, cognition, and sleep
      using a battery of validated clinical scales to assess efficacy of the probiotic alleviating
      depressive symptoms; sleep will also be assessed objectively with an ambulatory
      polysomnogram. Neuroimaging data will be collected using magnetic resonance imaging and
      electroencephalography to look at functional, structural, and electrical changes in the brain
      associated with consumption of the probiotic. Molecular data will be collected from blood,
      stool, and urine samples to look at levels of cytokines and serotonin, and explore potential
      genes and proteins that may predict outcomes in depression. An informatics-based approach
      will be used to integrate clinical, neuroimaging, and molecular data to look for biomarkers
      that indicate disease state and predict antidepressant-like response to the probiotic.
      Results: We expect results to replicate and expand on our pilot data, demonstrating that
      probiotics are effective in alleviating symptoms of depression, and to find biomarkers that
      will predict these outcomes. The findings from this study will contribute robust scientific
      data that is currently lacking in this emerging field.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: 16-week Double-blind randomized placebo-controlled dual-phase trial
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Mood
time frame: 16 weeks
description: Montgomery-Asberg Depression Rating Scale
measure: Anxiety
time frame: 16 weeks
description: Generalized Anxiety Disorder 7-item Scale
measure: Anhedonia
time frame: 16 weeks
description: Snaith Hamilton Pleasure Scale
measure: Cognition
time frame: 16 weeks
description: CNS Vital Signs
measure: Cytokines
time frame: 16 weeks
description: Blood plasma
measure: Serotonin
time frame: 16 weeks
description: Blood Plasma
measure: Microbiome
time frame: 16 weeks
description: Stool
measure: Brain structure/function
time frame: 8 weeks
description: fMRI
arm group label: Probio'Stick
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Probio'Stick
description: Probiotic supplement containing Lactobacillus helveticus and Bifidobacterium longum
arm group label: Probio'Stick
intervention type: Drug
intervention name: Placebo
description: Identically formulated and packaged inactive substance
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: Queen's University
investigator full name: Dr. Roumen Milev
investigator title: Head, Department of Psychiatry
mesh term: Depression
mesh term: Depressive Disorder
sharing ipd: No