<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/NCT04466345</url>
  </required_header>
  <id_info>
    <org_study_id>19-6283</org_study_id>
    <nct_id>NCT04466345</nct_id>
  </id_info>
  <brief_title>Semaglutide for the Treatment of Cognitive Dysfunction in Major Depressive Disorder</brief_title>
  <official_title>Adjunctive Semaglutide for the Treatment of Cognitive Dysfunction in Major Depressive Disorder: a Randomized, Double-Blind, Placebo-Controlled Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Health Network, Toronto</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Health Network, Toronto</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will examine whether semaglutide may improve cognitive function in individuals&#xD;
      with major depressive disorder (MDD).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a 16-week, placebo-controlled, randomized, double-blind, clinical trial, involving 60&#xD;
      overweight individuals with MDD and pre-treatment cognitive dysfunction. Study participants&#xD;
      will receive one of the following study interventions in addition to 'standard of care'&#xD;
      treatment: once-daily semaglutide, initiated at 3 mg/day for 4 weeks, increased to 7 mg/day&#xD;
      for 4 more weeks and titrated to 14 mg/day for the subsequent 8 weeks; or matching placebo.&#xD;
      Participants will be assessed to examine the effect of semaglutide on their cognitive&#xD;
      function.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 6, 2021</start_date>
  <completion_date type="Anticipated">October 5, 2024</completion_date>
  <primary_completion_date type="Anticipated">October 5, 2024</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>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Trail Making Test B (TMTB)</measure>
    <time_frame>12 Weeks</time_frame>
    <description>TMTB is a neurocognitive test designed to assess attention and concentration.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Digit Symbol Substitution Test (DSST)</measure>
    <time_frame>12 Weeks</time_frame>
    <description>DSST is a neurocognitive test designed to assess motor speed and concentration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rey Auditory Verbal Learning Test (RAVLT)</measure>
    <time_frame>12 Weeks</time_frame>
    <description>RAVLT is a neurocognitive test designed to assess verbal learning and memory.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stroop Test</measure>
    <time_frame>12 Weeks</time_frame>
    <description>The Stroop Test is a neurocognitive test designed to assess the ability to inhibit cognitive interference.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trail Making Test A (TMTA)</measure>
    <time_frame>12 Weeks</time_frame>
    <description>TMTA is a neurocognitive test designed to assess visual scanning and attention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Perceived Deficits Questionnaire (PDQ)</measure>
    <time_frame>12 Weeks</time_frame>
    <description>PDQ is used to assess subjective cognitive dysfunction.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>36-Item Short Form Health Survey (SF-36)</measure>
    <time_frame>12 Weeks</time_frame>
    <description>SF-36 is used to assess quality of life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sheehan Disability Scale (SDS)</measure>
    <time_frame>12 Weeks</time_frame>
    <description>SDS is used to assess functional impairment in work/school, social life, and family life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Endicott Workplace Productivity Scale (EWPS)</measure>
    <time_frame>12 Weeks</time_frame>
    <description>EWPS is used to assess workplace productivity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Height</measure>
    <time_frame>12 Weeks</time_frame>
    <description>Unit: cm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Weight</measure>
    <time_frame>12 Weeks</time_frame>
    <description>Unit: kg</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>fasting glucose - Blood laboratorial marker</measure>
    <time_frame>12 Weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Diet History Questionnaire III (DHQ)</measure>
    <time_frame>12 Weeks</time_frame>
    <description>DHQ is a freely available questionnaire used to assess dietary intake (https://epi.grants.cancer.gov/dhq3/).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physical Activity Questionnaire (IPAQ)</measure>
    <time_frame>12 Weeks</time_frame>
    <description>IPAQ is used to assess physical activity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pittsburgh Sleep Quality Index (PSQI)</measure>
    <time_frame>12 Weeks</time_frame>
    <description>PSQI is used to assess sleep quality.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Major Depressive Disorder</condition>
  <arm_group>
    <arm_group_label>Semaglutide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive semaglutide once daily orally, initiated at 3 mg/day for 4 weeks, increased to 7 mg/day for 4 more weeks and titrated to 14 mg/day for the subsequent 8 weeks (i.e., duration of 16 weeks in total).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants receive matching semaglutide placebo capsules once daily (duration of 16 weeks).</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Semaglutide</intervention_name>
    <description>3 mg/day for 4 weeks, increased to 7 mg/day for 4 more weeks and titrated to 14 mg/day for the subsequent 8 weeks</description>
    <arm_group_label>Semaglutide</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Semaglutide placebo capsules</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Informed consent before study-related activity&#xD;
&#xD;
          2. Individuals between the ages of 18 and 60 who meet Diagnostic and Statistical Manual&#xD;
             of Mental Disorders, 5th Edition (DSM-5) criteria for MDD&#xD;
&#xD;
          3. Overweight (i.e. BMI ≥ 25 kg/m2)&#xD;
&#xD;
          4. Below-average (i.e. &gt;1 SD below norm) performance in the Trail Making Test-B (TMTB)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Current, or in the past 4 weeks, treatment with other oral hypoglycemic agents and/or&#xD;
             insulin&#xD;
&#xD;
          2. Diagnosis of possible or probable Alzheimer's Disease, Mild Cognitive Impairment, or&#xD;
             any other dementia&#xD;
&#xD;
          3. History of neurological disorder, or evidence of neurologic or other physical illness&#xD;
             that could produce cognitive deterioration&#xD;
&#xD;
          4. Severe mood episode, defined as a Hamilton Depression Rating Scale (HAMD-17) score of&#xD;
             &gt;23&#xD;
&#xD;
          5. Actively suicidal or evaluated as being a suicide risk (operationalized as a score of&#xD;
             ≥3 on HAMD-17 suicide item and/or by clinical assessment).&#xD;
&#xD;
          6. Substance use disorder within 3 months before screening or a positive baseline&#xD;
             toxicology screen&#xD;
&#xD;
          7. DSM-5 diagnosis of obsessive compulsive disorder, posttraumatic stress disorder&#xD;
             (current or within the last year), or borderline personality disorder as assessed by a&#xD;
             study investigator&#xD;
&#xD;
          8. Presence of absolute or relative contraindication to semaglutide (e.g.&#xD;
             hypersensitivity to semaglutide, hepatic impairment, renal impairment with chronic&#xD;
             kidney disease stage 3 and above, personal or familial history of medullary thyroid&#xD;
             cancer or Multiple Endocrine Neoplasia syndrome type 2)&#xD;
&#xD;
          9. History of diabetic retinopathy&#xD;
&#xD;
         10. History of pancreatitis or pancreatic cancer&#xD;
&#xD;
         11. Presence of clinically unstable general medical illness&#xD;
&#xD;
         12. Pregnancy or breastfeeding women&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rodrigo B. Mansur, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Health Network, Toronto</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Rodrigo B. Mansur, MD, PhD</last_name>
    <phone>416 603 5106</phone>
    <email>rodrigo.mansur@uhn.ca</email>
  </overall_contact>
  <location>
    <facility>
      <name>Toronto Western Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5T 2S8</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joshua Di Vincenzo</last_name>
      <email>joshua.divincenzo@uhnresearch.ca</email>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>June 8, 2020</study_first_submitted>
  <study_first_submitted_qc>July 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 10, 2020</study_first_posted>
  <last_update_submitted>May 16, 2023</last_update_submitted>
  <last_update_submitted_qc>May 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>
    <mesh_term>Cognitive Dysfunction</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/NCT04466345
org study id: 19-6283
nct id: NCT04466345
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This study will examine whether semaglutide may improve cognitive function in individuals
      with major depressive disorder (MDD).
This is a 16-week, placebo-controlled, randomized, double-blind, clinical trial, involving 60
      overweight individuals with MDD and pre-treatment cognitive dysfunction. Study participants
      will receive one of the following study interventions in addition to 'standard of care'
      treatment: once-daily semaglutide, initiated at 3 mg/day for 4 weeks, increased to 7 mg/day
      for 4 more weeks and titrated to 14 mg/day for the subsequent 8 weeks; or matching placebo.
      Participants will be assessed to examine the effect of semaglutide on their cognitive
      function.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Trail Making Test B (TMTB)
time frame: 12 Weeks
description: TMTB is a neurocognitive test designed to assess attention and concentration.
measure: Digit Symbol Substitution Test (DSST)
time frame: 12 Weeks
description: DSST is a neurocognitive test designed to assess motor speed and concentration.
measure: Rey Auditory Verbal Learning Test (RAVLT)
time frame: 12 Weeks
description: RAVLT is a neurocognitive test designed to assess verbal learning and memory.
measure: Stroop Test
time frame: 12 Weeks
description: The Stroop Test is a neurocognitive test designed to assess the ability to inhibit cognitive interference.
measure: Trail Making Test A (TMTA)
time frame: 12 Weeks
description: TMTA is a neurocognitive test designed to assess visual scanning and attention.
measure: Perceived Deficits Questionnaire (PDQ)
time frame: 12 Weeks
description: PDQ is used to assess subjective cognitive dysfunction.
measure: 36-Item Short Form Health Survey (SF-36)
time frame: 12 Weeks
description: SF-36 is used to assess quality of life.
measure: Sheehan Disability Scale (SDS)
time frame: 12 Weeks
description: SDS is used to assess functional impairment in work/school, social life, and family life.
measure: Endicott Workplace Productivity Scale (EWPS)
time frame: 12 Weeks
description: EWPS is used to assess workplace productivity.
measure: Height
time frame: 12 Weeks
description: Unit: cm
measure: Weight
time frame: 12 Weeks
description: Unit: kg
measure: fasting glucose - Blood laboratorial marker
time frame: 12 Weeks
measure: Diet History Questionnaire III (DHQ)
time frame: 12 Weeks
description: DHQ is a freely available questionnaire used to assess dietary intake (https://epi.grants.cancer.gov/dhq3/).
measure: Physical Activity Questionnaire (IPAQ)
time frame: 12 Weeks
description: IPAQ is used to assess physical activity.
measure: Pittsburgh Sleep Quality Index (PSQI)
time frame: 12 Weeks
description: PSQI is used to assess sleep quality.
arm group label: Semaglutide
arm group type: Experimental
description: Participants receive semaglutide once daily orally, initiated at 3 mg/day for 4 weeks, increased to 7 mg/day for 4 more weeks and titrated to 14 mg/day for the subsequent 8 weeks (i.e., duration of 16 weeks in total).
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants receive matching semaglutide placebo capsules once daily (duration of 16 weeks).
intervention type: Biological
intervention name: Semaglutide
description: 3 mg/day for 4 weeks, increased to 7 mg/day for 4 more weeks and titrated to 14 mg/day for the subsequent 8 weeks
arm group label: Semaglutide
intervention type: Biological
intervention name: Placebo
description: Semaglutide placebo capsules
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Rodrigo B. Mansur, MD, PhD
role: Principal Investigator
affiliation: University Health Network, Toronto
last name: Rodrigo B. Mansur, MD, PhD
phone: 416 603 5106
email: rodrigo.mansur@uhn.ca
facility: 
status: Recruiting
contact: 
country: Canada
responsible party type: Sponsor
mesh term: Depressive Disorder
mesh term: Depression
mesh term: Depressive Disorder, Major
mesh term: Cognitive Dysfunction