<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/NCT03833063</url>
  </required_header>
  <id_info>
    <org_study_id>2019BR</org_study_id>
    <nct_id>NCT03833063</nct_id>
  </id_info>
  <brief_title>Glabellar Botulinum Toxin Injections for the Treatment of Geriatric Depression</brief_title>
  <acronym>BOTDEP</acronym>
  <official_title>Glabellar Botulinum Toxin Injections for the Treatment of Geriatric Depression</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Helse Stavanger HF</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Helse Stavanger HF</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>
      The effectiveness of glabellar injection of botulinum toxin type A (BTA) in treating&#xD;
      depression has not yet been investigated in elderly patients. The study aims in addressing&#xD;
      the question if glabellar injection of BTA is effective in treating geriatric depression.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Feedback from facial expressions is known to influence emotional experience. Treatment of&#xD;
      muscles involved in facial expression of sadness, anger or anxiety with botulinumtoxin showed&#xD;
      a quick, strong and sustained improvement in the symptoms of depression. As considerable&#xD;
      proportion of patients do not sufficiently respond to existing treatment options. Especially&#xD;
      in the elderly current treatments show limited response or are associated with side effects.&#xD;
      Injections with BTA are considered as a very safe treatment without lasting side effects. The&#xD;
      aim of the study is to investigate effectiveness of BTA in treating major depression in the&#xD;
      elderly in a cross-over designed, placebo-controlled manner.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    recruitment difficulties due to COVID19&#xD;
  </why_stopped>
  <start_date type="Anticipated">May 1, 2019</start_date>
  <completion_date type="Anticipated">March 31, 2020</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>placebo controlled, randomized, cross-over</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Severity og depressive symptoms, response to treatment</measure>
    <time_frame>16 weeks</time_frame>
    <description>Response to treatment, as defined as a 50% or greater decrease in Montgomery Aasberg Depression Rating Scale (MADRS) from baseline&#xD;
Montgomery-Åsberg Depression Rating Scale The Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire to measure the severity of depressive episodes in patients with mood disorders.&#xD;
Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60.[4] The questionnaire includes questions on the following symptoms 1. Apparent sadness 2. Reported sadness 3. Inner tension 4. Reduced sleep 5. Reduced appetite 6. Concentration difficulties 7. Lassitude 8. Inability to feel 9. Pessimistic thoughts 10. Suicidal thoughts&#xD;
Usual cutoff points are:&#xD;
0 to 6 - normal /symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression &gt;34 - severe depression.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>remission</measure>
    <time_frame>16 weeks</time_frame>
    <description>remission rate, as defined by a Montgomery Aasberg Depression Rating Scale MADRS score of 10 or lower</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>severity of depressive symptoms, self-rated Geriatric Depression Scale (GDS)</measure>
    <time_frame>16 weeks</time_frame>
    <description>severity of depressive symptoms, self-rated Geriatric Depression Scale (GDS) In the Geriatric Depression Scale, questions are answered &quot;yes&quot; or &quot;no.&quot; A five-category response set is not utilized in order to ensure that the scale is simple enough to be used when testing ill or moderately cognitively impaired individuals, for whom a more complex set of answers may be confusing, or lead to inaccurate recording of responses.&#xD;
The scale consists of 30 yes/no questions. Each question is scored as either 0 or 1 points. The following general cutoff may be used to qualify the severity:&#xD;
normal 0-9, mild depressives 10-19, severe depressives 20-30.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>quality of life, as assessed with QOL-AD</measure>
    <time_frame>16 weeks</time_frame>
    <description>quality of life, as assessed with the questionnaire QOL-AD Use of the QOL-AD for measuring quality of life in people with dementia Scoring instructions for QOL-AD: Points are assigned to each item as follows:poor=1,fair=2,good=3,excellent=4. The total score is the sum of all 13 items.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>safety/tolerability</measure>
    <time_frame>16 weeks</time_frame>
    <description>Incidence of Treatment-Emergent Adverse Events, as assessed by number in registration of AE/SAE</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Major Depressive Disorder</condition>
  <condition>Major Depressive Episode</condition>
  <condition>Treatment Resistant Depression</condition>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>injections with sodium chloride</description>
  </arm_group>
  <arm_group>
    <arm_group_label>botulinum toxin A</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>injections with botulinum toxin A</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>botulinum toxin A</intervention_name>
    <description>glabellar injections with botulinum toxin A</description>
    <arm_group_label>botulinum toxin A</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebos</intervention_name>
    <description>glabellar injections with sodium chloride</description>
    <arm_group_label>placebo</arm_group_label>
    <other_name>sodium chloride</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria: Clinically relevant depressive symptoms ( defined as MADRS &gt; 12)&#xD;
&#xD;
        Exclusion criteria: cognitive deficits that impair the participant´s ability to provide&#xD;
        written informed consent severe depression MADRS &gt;34 suicidality treatment with more than 3&#xD;
        psychotropic medications recent changes (4 weeks) in current psychotropic medication&#xD;
        previous treatment with study drug active substance abuse bipolar disorder schizophrenia&#xD;
        unstable medical condition usage of warfarin or NOAC bleeding disorder known&#xD;
        hypersensitivity to study drog or any of the excipients of the formulation myasthenia&#xD;
        gravis or Eaton Lambert syndrome presence of infection at the proposed injection sites&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>February 4, 2019</study_first_submitted>
  <study_first_submitted_qc>February 5, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 6, 2019</study_first_posted>
  <last_update_submitted>August 10, 2021</last_update_submitted>
  <last_update_submitted_qc>August 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 11, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>botulinumtoxin</keyword>
  <keyword>botox</keyword>
  <keyword>depression</keyword>
  <keyword>geriatric depression</keyword>
  <keyword>depression in older adults</keyword>
  <keyword>depression in the elderly</keyword>
  <keyword>old age depression</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
    <mesh_term>Depressive Disorder, Treatment-Resistant</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Botulinum Toxins</mesh_term>
    <mesh_term>Botulinum Toxins, Type A</mesh_term>
    <mesh_term>abobotulinumtoxinA</mesh_term>
  </intervention_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/NCT03833063
org study id: 2019BR
nct id: NCT03833063
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The effectiveness of glabellar injection of botulinum toxin type A (BTA) in treating
      depression has not yet been investigated in elderly patients. The study aims in addressing
      the question if glabellar injection of BTA is effective in treating geriatric depression.
Feedback from facial expressions is known to influence emotional experience. Treatment of
      muscles involved in facial expression of sadness, anger or anxiety with botulinumtoxin showed
      a quick, strong and sustained improvement in the symptoms of depression. As considerable
      proportion of patients do not sufficiently respond to existing treatment options. Especially
      in the elderly current treatments show limited response or are associated with side effects.
      Injections with BTA are considered as a very safe treatment without lasting side effects. The
      aim of the study is to investigate effectiveness of BTA in treating major depression in the
      elderly in a cross-over designed, placebo-controlled manner.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: placebo controlled, randomized, cross-over
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Severity og depressive symptoms, response to treatment
time frame: 16 weeks
description: Response to treatment, as defined as a 50% or greater decrease in Montgomery Aasberg Depression Rating Scale (MADRS) from baseline
Montgomery-Åsberg Depression Rating Scale The Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire to measure the severity of depressive episodes in patients with mood disorders.
Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60.[4] The questionnaire includes questions on the following symptoms 1. Apparent sadness 2. Reported sadness 3. Inner tension 4. Reduced sleep 5. Reduced appetite 6. Concentration difficulties 7. Lassitude 8. Inability to feel 9. Pessimistic thoughts 10. Suicidal thoughts
Usual cutoff points are:
0 to 6 - normal /symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression.
measure: remission
time frame: 16 weeks
description: remission rate, as defined by a Montgomery Aasberg Depression Rating Scale MADRS score of 10 or lower
measure: severity of depressive symptoms, self-rated Geriatric Depression Scale (GDS)
time frame: 16 weeks
description: severity of depressive symptoms, self-rated Geriatric Depression Scale (GDS) In the Geriatric Depression Scale, questions are answered "yes" or "no." A five-category response set is not utilized in order to ensure that the scale is simple enough to be used when testing ill or moderately cognitively impaired individuals, for whom a more complex set of answers may be confusing, or lead to inaccurate recording of responses.
The scale consists of 30 yes/no questions. Each question is scored as either 0 or 1 points. The following general cutoff may be used to qualify the severity:
normal 0-9, mild depressives 10-19, severe depressives 20-30.
measure: quality of life, as assessed with QOL-AD
time frame: 16 weeks
description: quality of life, as assessed with the questionnaire QOL-AD Use of the QOL-AD for measuring quality of life in people with dementia Scoring instructions for QOL-AD: Points are assigned to each item as follows:poor=1,fair=2,good=3,excellent=4. The total score is the sum of all 13 items.
measure: safety/tolerability
time frame: 16 weeks
description: Incidence of Treatment-Emergent Adverse Events, as assessed by number in registration of AE/SAE
arm group label: placebo
arm group type: Placebo Comparator
description: injections with sodium chloride
arm group label: botulinum toxin A
arm group type: Active Comparator
description: injections with botulinum toxin A
intervention type: Drug
intervention name: botulinum toxin A
description: glabellar injections with botulinum toxin A
arm group label: botulinum toxin A
intervention type: Drug
intervention name: Placebos
description: glabellar injections with sodium chloride
arm group label: placebo
other name: sodium chloride
criteria: 
gender: All
minimum age: 65 Years
maximum age: 99 Years
healthy volunteers: No
responsible party type: Sponsor
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Major
mesh term: Depressive Disorder, Treatment-Resistant
mesh term: Botulinum Toxins
mesh term: Botulinum Toxins, Type A
mesh term: abobotulinumtoxinA
sharing ipd: No