<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/NCT03031184</url>
  </required_header>
  <id_info>
    <org_study_id>15/SC/0606</org_study_id>
    <nct_id>NCT03031184</nct_id>
  </id_info>
  <brief_title>Study of Mirtazapine for Agitation in Dementia</brief_title>
  <acronym>SYMBAD</acronym>
  <official_title>A Pragmatic, Multi Centre, Double-blind, Placebo Controlled Randomised Trial to Assess the Safety, Clinical and Cost Effectiveness of Mirtazapine in Patients With Alzheimer's Disease (AD) and Agitated Behaviours</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Sussex</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Norwich Clinical Trials Unit</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of East Anglia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Cambridge</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University College, London</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>London School of Economics and Political Science</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Manchester</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Newcastle Upon-Tyne</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Birmingham and Solihull Mental Health NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Alzheimer's Society</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Centre for Dementia Studies, Brighton and Sussex Medical School and SPFT</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Sussex</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This clinical trial evaluates whether Mirtazapine is more effective than placebo in treating&#xD;
      agitation in people with dementia. The trial will assess the safety, clinical and cost&#xD;
      effectiveness of the treatment. Participants will be randomised to receive either Mirtazapine&#xD;
      or placebo for 12 weeks and will be followed up for up to one year, in this blinded trial.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patient-centred care, without the use of medicines is offered as a first course of treatment&#xD;
      for agitation in dementia. However, there is a need for second line treatments when these&#xD;
      fail, at the moment antipsychotics are commonly prescribed, as very little research has been&#xD;
      done in to safer alternative treatments.&#xD;
&#xD;
      There are medicines available to treat agitation and/or aggression in dementia, but it is not&#xD;
      clear which treatments work best.&#xD;
&#xD;
      This research study has been designed to help answer this, by comparing a which is currently&#xD;
      prescribed for depression, Mirtazapine, with placebo (a tablet designed to look like a&#xD;
      medicine but that has no active medicine in it) to see if Mirtazapine is suitable for&#xD;
      treating agitation in dementia.&#xD;
&#xD;
      If participants and their family/carers agree to take part in this study, participants will&#xD;
      be prescribed treatment for 12 weeks. Participants will then be followed up for 1 year after,&#xD;
      with assessment sessions at 26 and 52 weeks.&#xD;
&#xD;
      Participants taking part in this study will be randomly allocated to a treatment group&#xD;
      (selected to their treatment group by chance). The study is blinded, so this means the&#xD;
      participant's doctor and the research team will not know which treatment the participant has&#xD;
      been taking until after the study has ended. This is necessary so that the trial is a fair&#xD;
      test of which treatment works best, however it is possible to find out which medicine they&#xD;
      are taking in the event of a medical emergency.&#xD;
&#xD;
      The study is entirely voluntary and all participants wishing to join the study must complete&#xD;
      an informed consent form (or if they lack capacity the participant's representative may do so&#xD;
      on their behalf). Each participant must also have a nominated carer who consents to being&#xD;
      questioned on aspects of the participant's dementia/care and their own experiences in caring&#xD;
      for the participant.&#xD;
&#xD;
      The investigators are aiming to recruit 222 patients to the study in total from around 20&#xD;
      different regions across the UK.&#xD;
&#xD;
      The study was originally designed to included a second medication, called Carbamazepine, to&#xD;
      also look at whether it would work and be safe and cost effective in agitation in dementia.&#xD;
      Challenges in recruitment in this population resulted in the funder requesting that the&#xD;
      available data was reviewed to July 2018, to see whether one of the arms (Mirtazapine or&#xD;
      Carbamazepine) should be discontinued in terms of future recruitment. The independent data&#xD;
      monitoring committee compared blinded data from both groups against placebo data and&#xD;
      concluded that on the basis of efficacy and safety, the group, which when unblinded was found&#xD;
      to be Carbamazepine, should be dropped. Some limited analysis will still be completed for all&#xD;
      data collected in the Carbamazepine group, but the trial will continue now only randomising&#xD;
      participants to Mirtazapine or placebo.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2017</start_date>
  <completion_date type="Actual">March 2021</completion_date>
  <primary_completion_date type="Actual">June 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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cohen Mansfield Agitation Inventory (CMAI) score (Long Form, 29 questions)</measure>
    <time_frame>Baseline, 6 weeks, 12 weeks</time_frame>
    <description>Measured at baseline, 6 and 12 weeks, it is the difference in the score at 12 weeks that is the primary outcome. The questions are asked of the person with dementia's carer</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">207</enrollment>
  <condition>Dementia</condition>
  <arm_group>
    <arm_group_label>Mirtazapine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>15mg of Mirtazapine over encapsulated to produce a blinded product that looks identical to the other arms. Starting dose is one capsule per day, escalating to 2 capsules per day after 2 weeks if no side effects and up to 3 capsules per day after 4 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Lactose powder encapsulated to produce a blinded product that looks identical to the other arms. Starting dose is one capsule per day, escalating to 2 capsules per day after 2 weeks if no side effects and up to 3 capsules per day after 4 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mirtazapine</intervention_name>
    <arm_group_label>Mirtazapine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Dummy pill</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with a clinical diagnosis of probable or possible Alzheimer's Disease using&#xD;
             National Institute of Neurological and Communicative Disorders and Stroke and the&#xD;
             Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria (McKhann&#xD;
             et Al, 1984)&#xD;
&#xD;
          -  a diagnosis of co-existing agitated behaviours&#xD;
&#xD;
          -  evidence that the agitated behaviours have not responded to management according to&#xD;
             the AS/DH algorithm (AS/DH, 2011)&#xD;
&#xD;
          -  An assessment of Cohen Mansfield Agitation Inventory (CMAI; Cohen-Mansfield et al,&#xD;
             1989, Long form) score of 45 or greater&#xD;
&#xD;
          -  Written informed consent to enter and be randomised into the trial&#xD;
&#xD;
          -  Availability of a suitable informant (consenting identifiable family carer or paid&#xD;
             carer) to provide information on carer-completed outcome measures and who consents to&#xD;
             take part in the trial.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current treatment with antidepressants (including MAOIs) or antipsychotics. Normal&#xD;
             clinical practice should be followed, with an appropriate washout period before trial&#xD;
             drug administration. For MAOIs this should be least two weeks.&#xD;
&#xD;
          -  Contraindications to the administration of mirtazapine as per the current SmPC&#xD;
&#xD;
          -  Patients with second degree atrioventricular block (patients with third degree heart&#xD;
             block, with a pace maker fitted, may be included at PI discretion)&#xD;
&#xD;
          -  Cases too critical for randomisation (ie where there is a suicide risk or where the&#xD;
             patient presents a risk of harm to others)&#xD;
&#xD;
          -  Female subjects under the age of 55 of childbearing potential, defined as follows:&#xD;
             postmenopausal females who have not had at least 12 months of spontaneous amenorrhea&#xD;
             or 6 months of spontaneous amenorrhoea with serum FSH&gt;40mIU/ml or females who have not&#xD;
             had a hysterectomy or bilateral oophorectomy at least 6 weeks prior to enrolment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sube Banerjee, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Brighton and Sussex Medical School</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sube Banerjee</name>
      <address>
        <city>Brighton</city>
        <state>Sussex</state>
        <zip>BN1 9RY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>January 3, 2017</study_first_submitted>
  <study_first_submitted_qc>January 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 25, 2017</study_first_posted>
  <last_update_submitted>April 16, 2021</last_update_submitted>
  <last_update_submitted_qc>April 16, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 19, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Agitation</keyword>
  <keyword>Agitated behaviours</keyword>
  <keyword>Alzheimer's Disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dementia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mirtazapine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The datasets generated during the current study will be available upon request from Prof Sube Banerjee sube.banerjee@plymouth.ac.uk once the trial follow-up and analyses are completed, the likely date for this is October 2022.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>After analysis by the study team is complete, likely from October 2022. The above documents are already available</ipd_time_frame>
    <ipd_access_criteria>By email request to Prof Sube Banerjee sube.banerjee@plymouth.ac.uk</ipd_access_criteria>
  </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/NCT03031184
org study id: 15/SC/0606
nct id: NCT03031184
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
This clinical trial evaluates whether Mirtazapine is more effective than placebo in treating
      agitation in people with dementia. The trial will assess the safety, clinical and cost
      effectiveness of the treatment. Participants will be randomised to receive either Mirtazapine
      or placebo for 12 weeks and will be followed up for up to one year, in this blinded trial.
Patient-centred care, without the use of medicines is offered as a first course of treatment
      for agitation in dementia. However, there is a need for second line treatments when these
      fail, at the moment antipsychotics are commonly prescribed, as very little research has been
      done in to safer alternative treatments.

      There are medicines available to treat agitation and/or aggression in dementia, but it is not
      clear which treatments work best.

      This research study has been designed to help answer this, by comparing a which is currently
      prescribed for depression, Mirtazapine, with placebo (a tablet designed to look like a
      medicine but that has no active medicine in it) to see if Mirtazapine is suitable for
      treating agitation in dementia.

      If participants and their family/carers agree to take part in this study, participants will
      be prescribed treatment for 12 weeks. Participants will then be followed up for 1 year after,
      with assessment sessions at 26 and 52 weeks.

      Participants taking part in this study will be randomly allocated to a treatment group
      (selected to their treatment group by chance). The study is blinded, so this means the
      participant's doctor and the research team will not know which treatment the participant has
      been taking until after the study has ended. This is necessary so that the trial is a fair
      test of which treatment works best, however it is possible to find out which medicine they
      are taking in the event of a medical emergency.

      The study is entirely voluntary and all participants wishing to join the study must complete
      an informed consent form (or if they lack capacity the participant's representative may do so
      on their behalf). Each participant must also have a nominated carer who consents to being
      questioned on aspects of the participant's dementia/care and their own experiences in caring
      for the participant.

      The investigators are aiming to recruit 222 patients to the study in total from around 20
      different regions across the UK.

      The study was originally designed to included a second medication, called Carbamazepine, to
      also look at whether it would work and be safe and cost effective in agitation in dementia.
      Challenges in recruitment in this population resulted in the funder requesting that the
      available data was reviewed to July 2018, to see whether one of the arms (Mirtazapine or
      Carbamazepine) should be discontinued in terms of future recruitment. The independent data
      monitoring committee compared blinded data from both groups against placebo data and
      concluded that on the basis of efficacy and safety, the group, which when unblinded was found
      to be Carbamazepine, should be dropped. Some limited analysis will still be completed for all
      data collected in the Carbamazepine group, but the trial will continue now only randomising
      participants to Mirtazapine or placebo.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Cohen Mansfield Agitation Inventory (CMAI) score (Long Form, 29 questions)
time frame: Baseline, 6 weeks, 12 weeks
description: Measured at baseline, 6 and 12 weeks, it is the difference in the score at 12 weeks that is the primary outcome. The questions are asked of the person with dementia's carer
arm group label: Mirtazapine
arm group type: Experimental
description: 15mg of Mirtazapine over encapsulated to produce a blinded product that looks identical to the other arms. Starting dose is one capsule per day, escalating to 2 capsules per day after 2 weeks if no side effects and up to 3 capsules per day after 4 weeks.
arm group label: Placebo
arm group type: Placebo Comparator
description: Lactose powder encapsulated to produce a blinded product that looks identical to the other arms. Starting dose is one capsule per day, escalating to 2 capsules per day after 2 weeks if no side effects and up to 3 capsules per day after 4 weeks.
intervention type: Drug
intervention name: Mirtazapine
arm group label: Mirtazapine
intervention type: Other
intervention name: Placebo
arm group label: Placebo
other name: Dummy pill
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sube Banerjee, Professor
role: Principal Investigator
affiliation: Brighton and Sussex Medical School
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Dementia
mesh term: Mirtazapine
sharing ipd: Yes
ipd description: The datasets generated during the current study will be available upon request from Prof Sube Banerjee sube.banerjee@plymouth.ac.uk once the trial follow-up and analyses are completed, the likely date for this is October 2022.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: After analysis by the study team is complete, likely from October 2022. The above documents are already available
ipd access criteria: By email request to Prof Sube Banerjee sube.banerjee@plymouth.ac.uk