<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/NCT02228005</url>
  </required_header>
  <id_info>
    <org_study_id>DF-2013-10</org_study_id>
    <nct_id>NCT02228005</nct_id>
  </id_info>
  <brief_title>The Effect of a Selective Serotonin Reuptake Inhibitor on Gait, Balance, and Bone Metabolism in Older Adults</brief_title>
  <official_title>The Effect of a Selective Serotonin Reuptake Inhibitor on Gait, Balance, and Bone Metabolism in Older Adults</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>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to examine the effects of sertraline treatment of depression in&#xD;
      older adults on gait stability, balance recovery reactions, and markers of bone metabolism.&#xD;
      This is a pilot study that will determine feasibility and generate hypotheses for a larger&#xD;
      definitive study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressant medication&#xD;
      frequently used to treat depressive and anxiety disorders in the elderly. Although widely&#xD;
      considered to be a safe option, several observational studies have found that SSRIs have as&#xD;
      strong an association with falls as other psychotropic medications including tricyclic&#xD;
      antidepressants and benzodiazepines. However, the potential mechanism for a link between&#xD;
      SSRIs and falls is unclear. Compared to other psychotropic medications, SSRIs have lower&#xD;
      rates of side effects that could contribute to falls, including sedation, orthostatic blood&#xD;
      pressure changes, and anticholinergicity. Interestingly, SSRIs have also been associated with&#xD;
      fractures, more so than other classes of antidepressants, in both administrative database&#xD;
      studies and prospective cohort studies that control for falls history. Serotonin is known to&#xD;
      play a role in regulating bone mass and some studies have found a loss of bone mass in&#xD;
      individuals on SSRI treatment.&#xD;
&#xD;
      The association of SSRIs with falls and fractures is confounded by depression which is itself&#xD;
      associated with falls, gait instability, bone loss and fractures. The goal of this study is&#xD;
      to disentangle the contribution of the disease versus the treatment to risk of falls and&#xD;
      fractures. As a first step towards this goal, this pilot study will: i) estimate effect sizes&#xD;
      for statistical power calculations for an adequately powered study; and ii) examine the&#xD;
      feasibility of timely recruitment of older patients with major depression who have not taken&#xD;
      antidepressant medication for a minimum of 2 weeks prior to entering the study.&#xD;
&#xD;
      To address our research question, we have designed a prospective observational pilot study.&#xD;
      Older adults with depression will be assessed at baseline, and then 3,6, and 12 weeks after&#xD;
      initiation of sertraline antidepressant therapy. A non-depressed comparison group will be&#xD;
      used to control for the learning effects of repeated assessment. The outcomes of interest are&#xD;
      changes in gait, static balance, and dynamic balance recovery reactions. Our primary outcomes&#xD;
      are the short-term changes in these variables at 3 weeks, but we will also perform a&#xD;
      longitudinal analysis to assess change over 12 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">July 2016</completion_date>
  <primary_completion_date type="Actual">July 2016</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in number of steps to recover balance compared to baseline</measure>
    <time_frame>Baseline, 3 weeks</time_frame>
    <description>Number of steps</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in CTX-I (Serum collagen type-I cross-linked C-telopeptide)</measure>
    <time_frame>12 weeks</time_frame>
    <description>pg/ml</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in P1NP (Serum procollagen type-1 N-terminal polypeptide)</measure>
    <time_frame>12 weeks</time_frame>
    <description>ng/ml</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in stride variability from baseline</measure>
    <time_frame>Baseline, 3 weeks</time_frame>
    <description>ms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in centre of pressure sway velocity under dual task conditions</measure>
    <time_frame>Baseline, 3 weeks</time_frame>
    <description>cm/s</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Depression</condition>
  <arm_group>
    <arm_group_label>Depression</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sertraline 50- 200mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Comparison group (non-depressed)</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>No intervention</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sertraline</intervention_name>
    <description>Protocolized titration from 50 to max 200mg based on response and tolerance.</description>
    <arm_group_label>Depression</arm_group_label>
    <other_name>Zoloft</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Depressed group&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Clinical diagnosis of Major Depression&#xD;
&#xD;
          -  English-speaking&#xD;
&#xD;
          -  If currently on an antidepressant, willing to undergo a 2 week washout.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Lifetime bipolar disorder&#xD;
&#xD;
          -  Current psychotic disorder or substance use disorder&#xD;
&#xD;
          -  Dementia&#xD;
&#xD;
          -  Poor baseline mobility or baseline severe gait disorder&#xD;
&#xD;
          -  On treatment with fluoxetine or mood stabilizer&#xD;
&#xD;
          -  Severe renal impairment, bleeding disorder, recent gastric bleeding or hemorrhagic&#xD;
             stroke in past 3 months&#xD;
&#xD;
          -  Poor response or serious adverse event with sertraline in the past.&#xD;
&#xD;
        Comparison group&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
        - English-speaking&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Lifetime diagnosis of depression or dementia&#xD;
&#xD;
          -  Currently on antidepressant medication or mood stabilizer&#xD;
&#xD;
          -  Poor baseline mobility or baseline severe gait disorder&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Andrea Iaboni, MD DPhil</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Health Network and University of Toronto</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Toronto Rehabilitation Institute, University Health Network</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G2A2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>December 2015</verification_date>
  <study_first_submitted>July 23, 2014</study_first_submitted>
  <study_first_submitted_qc>August 27, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 28, 2014</study_first_posted>
  <last_update_submitted>May 3, 2017</last_update_submitted>
  <last_update_submitted_qc>May 3, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 4, 2017</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>Depression</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sertraline</mesh_term>
  </intervention_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/NCT02228005
org study id: DF-2013-10
nct id: NCT02228005
lead sponsor: 
has dmc: No
The purpose of this study is to examine the effects of sertraline treatment of depression in
      older adults on gait stability, balance recovery reactions, and markers of bone metabolism.
      This is a pilot study that will determine feasibility and generate hypotheses for a larger
      definitive study.
Selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressant medication
      frequently used to treat depressive and anxiety disorders in the elderly. Although widely
      considered to be a safe option, several observational studies have found that SSRIs have as
      strong an association with falls as other psychotropic medications including tricyclic
      antidepressants and benzodiazepines. However, the potential mechanism for a link between
      SSRIs and falls is unclear. Compared to other psychotropic medications, SSRIs have lower
      rates of side effects that could contribute to falls, including sedation, orthostatic blood
      pressure changes, and anticholinergicity. Interestingly, SSRIs have also been associated with
      fractures, more so than other classes of antidepressants, in both administrative database
      studies and prospective cohort studies that control for falls history. Serotonin is known to
      play a role in regulating bone mass and some studies have found a loss of bone mass in
      individuals on SSRI treatment.

      The association of SSRIs with falls and fractures is confounded by depression which is itself
      associated with falls, gait instability, bone loss and fractures. The goal of this study is
      to disentangle the contribution of the disease versus the treatment to risk of falls and
      fractures. As a first step towards this goal, this pilot study will: i) estimate effect sizes
      for statistical power calculations for an adequately powered study; and ii) examine the
      feasibility of timely recruitment of older patients with major depression who have not taken
      antidepressant medication for a minimum of 2 weeks prior to entering the study.

      To address our research question, we have designed a prospective observational pilot study.
      Older adults with depression will be assessed at baseline, and then 3,6, and 12 weeks after
      initiation of sertraline antidepressant therapy. A non-depressed comparison group will be
      used to control for the learning effects of repeated assessment. The outcomes of interest are
      changes in gait, static balance, and dynamic balance recovery reactions. Our primary outcomes
      are the short-term changes in these variables at 3 weeks, but we will also perform a
      longitudinal analysis to assess change over 12 weeks.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in number of steps to recover balance compared to baseline
time frame: Baseline, 3 weeks
description: Number of steps
measure: Change in CTX-I (Serum collagen type-I cross-linked C-telopeptide)
time frame: 12 weeks
description: pg/ml
measure: Change in P1NP (Serum procollagen type-1 N-terminal polypeptide)
time frame: 12 weeks
description: ng/ml
measure: Change in stride variability from baseline
time frame: Baseline, 3 weeks
description: ms
measure: Change in centre of pressure sway velocity under dual task conditions
time frame: Baseline, 3 weeks
description: cm/s
arm group label: Depression
arm group type: Experimental
description: Sertraline 50- 200mg
arm group label: Comparison group (non-depressed)
arm group type: No Intervention
description: No intervention
intervention type: Drug
intervention name: Sertraline
description: Protocolized titration from 50 to max 200mg based on response and tolerance.
arm group label: Depression
other name: Zoloft
criteria: 
gender: All
minimum age: 65 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Andrea Iaboni, MD DPhil
role: Principal Investigator
affiliation: University Health Network and University of Toronto
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Depression
mesh term: Sertraline