<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/NCT03040388</url>
  </required_header>
  <id_info>
    <org_study_id>DK-ECT-MR-1</org_study_id>
    <nct_id>NCT03040388</nct_id>
  </id_info>
  <brief_title>Exploring Effects of Electroconvulsive Therapy on the Human Brain in Depression - The Danish ECT/MRI Study</brief_title>
  <official_title>Predicting Effects and Risk of Relapse Into Depression - The Danish ECT/MRI Project</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Copenhagen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Mental Health Centre Glostrup</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Glostrup University Hospital, Copenhagen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Mental Health Centre Amager</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Mental Health Centre Copenhagen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Copenhagen</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main purpose of this study is to determine whether electroconvulsive therapy (ECT) causes&#xD;
      any structural or functional brain changes and thus indicating its mechanism of action. The&#xD;
      second aim is to find predictors of an immediate response, sustained remission, relapse and&#xD;
      side-effects. Thirdly, this study aims to explore whether ECT causes any changes in&#xD;
      blood-brain barriers permeability and whether these changes correlate to memory problems. The&#xD;
      fourth objective is to examine whether ECT causes any brain tissue damage.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      ECT has been the most effective treatment of depression for decades. Despite of this, neither&#xD;
      the mechanism of action or side-effects are fully elucidated. The reason why some patients&#xD;
      relapse shortly after remission is still not completely understood. Thus, there is a need to&#xD;
      find predictors of the favourable clinical effect, relapse and side-effects. ECT is&#xD;
      considered by professionals to be a safe procedure. However, this view is based on rather old&#xD;
      and small studies. Additionally, many patients do not consent to this treatment because they&#xD;
      fear a permanent loss of memory or that they will contract a brain damage after the completed&#xD;
      ECT series. Therefore, it is very important to examine whether ECT might have negative&#xD;
      effects on the structure or function of the brain, using state of the art Magnetic Resonance&#xD;
      Imaging (MRI) techniques on a greater study population.&#xD;
&#xD;
      The study consists of 60 inpatients, diagnosed with depression, admitted to one of the&#xD;
      recruiting Mental Health Centres, and scheduled to ECT. The most modern MRI sequences&#xD;
      examining brain structure and function are used at 3 time points: at baseline (just before&#xD;
      ECT series), the second examination (just after ECT series) and the third (follow-up)&#xD;
      examination (6 months after ECT series). Blood samples (measurements of Brain-Derived&#xD;
      Neurotrophic Factor - BDNF, Vascular Endothelial Growth Factor - VEGF along with the marker&#xD;
      of brain injury - S100B-protein) and the evaluation of clinical effect and side-effects to&#xD;
      ECT are performed at the same time points.&#xD;
&#xD;
      The study has 4 main hypotheses. The first hypothesis assumes that the immediate and&#xD;
      sustained response to ECT can be predicted by combining neuroimaging findings and&#xD;
      blood-samples results. The second hypothesis is based on the assumption that ECT modulates&#xD;
      the microstructure and connectivity in the fronto-limbic pathways (FLPs) and that this&#xD;
      modulation correlates with the clinical effect. Thus, the altered microstructure of the FLPs&#xD;
      in depression is normalised by an ECT series. Furthermore, the depression-associated&#xD;
      increased resting state connectivity in FLPs is normalised by ECT. The third hypothesis is&#xD;
      that ECT will induce changes in blood-brain barrier (BBB) permeability, which will correlate&#xD;
      with the severity of memory problems. The last hypothesis assumes that ECT does not cause any&#xD;
      brain tissue damage (including brain atrophy and white matter lesions - WMLs).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 9, 2017</start_date>
  <completion_date type="Actual">June 11, 2020</completion_date>
  <primary_completion_date type="Actual">October 30, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Volumetric changes in the hippocampus.</measure>
    <time_frame>at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)</time_frame>
    <description>This outcome will be measured by means of voxel-based morphometry (VBM).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in BDNF concentration in the blood.</measure>
    <time_frame>at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in regional cerebral blood flow (rCBF) in the frontal lobes.</measure>
    <time_frame>at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)</time_frame>
    <description>Pseudo-continuous arterial spin-labelling (PSCAL) will be used to measure this outcome.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The number of WMLs in the brain.</measure>
    <time_frame>at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)</time_frame>
    <description>FLAIR sequences of MRI will be used to measure this outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in water diffusion in the brain.</measure>
    <time_frame>at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)</time_frame>
    <description>Diffusion-weighted imaging (DWI) will be used to measure this outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in the level of fractional anisotropy (FA) in the brain.</measure>
    <time_frame>at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)</time_frame>
    <description>Diffusion tensor imaging (DTI) will be used to measure this outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in the level of intrinsic connectivity pattern in fronto-limbic pathways in the brain.</measure>
    <time_frame>at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)</time_frame>
    <description>Resting state functional MRI will be used to measure this outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in the glucose metabolism in the brain.</measure>
    <time_frame>at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)</time_frame>
    <description>Cerebral Metabolic Rate of Oxygen ( CMRO2) will be used to measure this outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in blood-brain barrier (BBB) permeability.</measure>
    <time_frame>at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)</time_frame>
    <description>Dynamic Contrast Enhanced (DCE)T1-weighted imaging will be used to measure this outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in S100B-protein concentration in the blood.</measure>
    <time_frame>at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)</time_frame>
  </secondary_outcome>
  <enrollment type="Actual">26</enrollment>
  <condition>Depressive Disorder</condition>
  <condition>Depression</condition>
  <condition>Depressive Disorder, Major</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Whole blood samples are kept in the biobank until the last enrolled patient has been&#xD;
      examined. They will be then analysed for S100B-protein concentration and destroyed. Whole&#xD;
      blood, serum and plasma samples are kept in the biobank until the last enrolled patient has&#xD;
      been examined. They will then be analysed for concentrations of BDNF and VEGF and destroyed.&#xD;
      Extra whole blood samples are stored in the psychiatric biobank for the future research (as&#xD;
      part of another protocol - PSV-2001-04, I-Suite 00422 - ID nr 2001-54-798)&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The study population consists of the inpatients admitted to one of the recruiting Mental&#xD;
        Health Centres (MHC) in the Capital Region of Denmark (Mental Health Centre Glostrup or&#xD;
        Amager or Copenhagen or others), diagnosed with either depression according to the 10th&#xD;
        version of the International Classification of Diseases (ICD-10) or major depression&#xD;
        according to the Diagnostic and Statistical Manual of Mental Disorders, 4th ed (DSM-IV) and&#xD;
        scheduled to ECT series.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  age 18-95 years&#xD;
&#xD;
          -  admitted at the MHC Glostrup, MHC Amager or MHC Copenhagen (or other Mental Health&#xD;
             Centres in the Capital Region)&#xD;
&#xD;
          -  fulfilling the criteria for depression according to ICD-10 and major depression&#xD;
             according to DSM-IV and where ECT is planned.&#xD;
&#xD;
          -  must be able to give informed consent to participate in the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Schizophrenia or any other psychotic disorder except for psychotic depression&#xD;
&#xD;
          -  Dependency syndrome according to ICD-10.&#xD;
&#xD;
          -  Severe somatic or neurological condition (e.g. stroke) confounding results&#xD;
&#xD;
          -  Head trauma resulting in unconsciousness for more than 5 minutes&#xD;
&#xD;
          -  Severe psychotic symptoms or suicide impulses making transportation hazardous&#xD;
&#xD;
          -  Contraindications against MRI or Gadovist infusion&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Maintenance ECT or ECT received during the last 6 months&#xD;
&#xD;
          -  Any form of compulsory treatment&#xD;
&#xD;
          -  Subjects who do not consent to be informed of incidental findings that could have&#xD;
             healthcare implications will not be scanned and can thus not be included&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>95 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Poul Videbech, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mental Health Centre Glostrup</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mental Health Centre Glostrup</name>
      <address>
        <city>Glostrup</city>
        <state>The Capital Region</state>
        <zip>2600</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <link>
    <url>http://www.sst.dk/~/media/6F9CE14B6FF245AABCD222575787FEB7.ashx</url>
    <description>Sundhedsstyrelsen: Referenceprogram for Unipolar Depression hos voksne. 2007.</description>
  </link>
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    <description>Ottosson J-O, Fink M. Ethics in electroconvulsive therapy. New York: Brunner-Reoutledge, 2004.</description>
  </link>
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  <verification_date>September 2020</verification_date>
  <study_first_submitted>January 30, 2017</study_first_submitted>
  <study_first_submitted_qc>February 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 2, 2017</study_first_posted>
  <last_update_submitted>September 21, 2020</last_update_submitted>
  <last_update_submitted_qc>September 21, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Copenhagen</investigator_affiliation>
    <investigator_full_name>Poul Videbech</investigator_full_name>
    <investigator_title>Professor, consultant in psychiatry</investigator_title>
  </responsible_party>
  <keyword>Electroconvulsive therapy</keyword>
  <keyword>Depressive Disorder</keyword>
  <keyword>Magnetic Resonance Imaging</keyword>
  <keyword>Hippocampus</keyword>
  <keyword>Brain-Derived Neurotrophic Factor</keyword>
  <keyword>Vascular Endothelial Growth Factor</keyword>
  <keyword>Blood-Brain Barrier</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>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>There is no plan to share Individual Patient Data.</ipd_description>
  </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/NCT03040388
org study id: DK-ECT-MR-1
nct id: NCT03040388
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
The main purpose of this study is to determine whether electroconvulsive therapy (ECT) causes
      any structural or functional brain changes and thus indicating its mechanism of action. The
      second aim is to find predictors of an immediate response, sustained remission, relapse and
      side-effects. Thirdly, this study aims to explore whether ECT causes any changes in
      blood-brain barriers permeability and whether these changes correlate to memory problems. The
      fourth objective is to examine whether ECT causes any brain tissue damage.
ECT has been the most effective treatment of depression for decades. Despite of this, neither
      the mechanism of action or side-effects are fully elucidated. The reason why some patients
      relapse shortly after remission is still not completely understood. Thus, there is a need to
      find predictors of the favourable clinical effect, relapse and side-effects. ECT is
      considered by professionals to be a safe procedure. However, this view is based on rather old
      and small studies. Additionally, many patients do not consent to this treatment because they
      fear a permanent loss of memory or that they will contract a brain damage after the completed
      ECT series. Therefore, it is very important to examine whether ECT might have negative
      effects on the structure or function of the brain, using state of the art Magnetic Resonance
      Imaging (MRI) techniques on a greater study population.

      The study consists of 60 inpatients, diagnosed with depression, admitted to one of the
      recruiting Mental Health Centres, and scheduled to ECT. The most modern MRI sequences
      examining brain structure and function are used at 3 time points: at baseline (just before
      ECT series), the second examination (just after ECT series) and the third (follow-up)
      examination (6 months after ECT series). Blood samples (measurements of Brain-Derived
      Neurotrophic Factor - BDNF, Vascular Endothelial Growth Factor - VEGF along with the marker
      of brain injury - S100B-protein) and the evaluation of clinical effect and side-effects to
      ECT are performed at the same time points.

      The study has 4 main hypotheses. The first hypothesis assumes that the immediate and
      sustained response to ECT can be predicted by combining neuroimaging findings and
      blood-samples results. The second hypothesis is based on the assumption that ECT modulates
      the microstructure and connectivity in the fronto-limbic pathways (FLPs) and that this
      modulation correlates with the clinical effect. Thus, the altered microstructure of the FLPs
      in depression is normalised by an ECT series. Furthermore, the depression-associated
      increased resting state connectivity in FLPs is normalised by ECT. The third hypothesis is
      that ECT will induce changes in blood-brain barrier (BBB) permeability, which will correlate
      with the severity of memory problems. The last hypothesis assumes that ECT does not cause any
      brain tissue damage (including brain atrophy and white matter lesions - WMLs).
observational model: Cohort
time perspective: Prospective
measure: Volumetric changes in the hippocampus.
time frame: at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)
description: This outcome will be measured by means of voxel-based morphometry (VBM).
measure: Changes in BDNF concentration in the blood.
time frame: at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)
measure: Changes in regional cerebral blood flow (rCBF) in the frontal lobes.
time frame: at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)
description: Pseudo-continuous arterial spin-labelling (PSCAL) will be used to measure this outcome.
measure: The number of WMLs in the brain.
time frame: at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)
description: FLAIR sequences of MRI will be used to measure this outcome.
measure: Changes in water diffusion in the brain.
time frame: at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)
description: Diffusion-weighted imaging (DWI) will be used to measure this outcome.
measure: Changes in the level of fractional anisotropy (FA) in the brain.
time frame: at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)
description: Diffusion tensor imaging (DTI) will be used to measure this outcome.
measure: Changes in the level of intrinsic connectivity pattern in fronto-limbic pathways in the brain.
time frame: at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)
description: Resting state functional MRI will be used to measure this outcome.
measure: Changes in the glucose metabolism in the brain.
time frame: at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)
description: Cerebral Metabolic Rate of Oxygen ( CMRO2) will be used to measure this outcome.
measure: Changes in blood-brain barrier (BBB) permeability.
time frame: at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)
description: Dynamic Contrast Enhanced (DCE)T1-weighted imaging will be used to measure this outcome.
measure: Changes in S100B-protein concentration in the blood.
time frame: at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)
Whole blood samples are kept in the biobank until the last enrolled patient has been
      examined. They will be then analysed for S100B-protein concentration and destroyed. Whole
      blood, serum and plasma samples are kept in the biobank until the last enrolled patient has
      been examined. They will then be analysed for concentrations of BDNF and VEGF and destroyed.
      Extra whole blood samples are stored in the psychiatric biobank for the future research (as
      part of another protocol - PSV-2001-04, I-Suite 00422 - ID nr 2001-54-798)
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 95 Years
healthy volunteers: No
last name: Poul Videbech, Professor
role: Principal Investigator
affiliation: Mental Health Centre Glostrup
facility: 
country: Denmark
url: http://www.sst.dk/~/media/6F9CE14B6FF245AABCD222575787FEB7.ashx
description: Sundhedsstyrelsen: Referenceprogram for Unipolar Depression hos voksne. 2007.
url: http://www.amazon.com/Ethics-Electroconvulsive-Therapy-Jan-Otto-Ottosson/dp/041594659X
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responsible party type: Principal Investigator
investigator affiliation: University of Copenhagen
investigator full name: Poul Videbech
investigator title: Professor, consultant in psychiatry
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Major
sharing ipd: No
ipd description: There is no plan to share Individual Patient Data.