<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/NCT02999269</url>
  </required_header>
  <id_info>
    <org_study_id>5U01MH111826</org_study_id>
    <secondary_id>5U01MH111826</secondary_id>
    <nct_id>NCT02999269</nct_id>
  </id_info>
  <brief_title>ECT Pulse Amplitude and Medial Temporal Lobe Engagement</brief_title>
  <official_title>ECT Pulse Amplitude and Medial Temporal Lobe Engagement</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of New Mexico</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Mind Research Network</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Texas</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Mental Health (NIMH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of New Mexico</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Electroconvulsive therapy (ECT) remains the gold-standard treatment for patients with&#xD;
      depressive episodes. During a typical four-week ECT series, most depressive episodes will&#xD;
      respond to treatment and people will improve their level of functioning (return to work or&#xD;
      family). Independent of the antidepressant effect of ECT, many patients experience transient&#xD;
      memory impairment. This investigation will examine the impact of one ECT parameter (pulse&#xD;
      amplitude or current) on brain changes (structure of connections within the brain) and&#xD;
      clinical outcomes. The goal of this investigation is to determine the optimal parameter for&#xD;
      an individual patient that will maintain the clinical response (reduce depression severity)&#xD;
      and minimize side effects (eliminate memory issues related to treatment).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Electroconvulsive therapy (ECT) remains the gold-standard treatment for patients with&#xD;
      depressive episodes. During a typical four-week ECT series, most depressive episodes remit,&#xD;
      and formerly suicidal or psychotically depressed patients will resume their premorbid levels&#xD;
      of functioning. Independent of the antidepressant effect of ECT, many patients experience&#xD;
      debilitating but transient cognitive effects such as attention and memory deficits. These&#xD;
      unwanted side effects are particularly troubling for older patients who are more likely to&#xD;
      have existing cognitive deficits. Both the stimulus delivery (electrode placement, pulse&#xD;
      amplitude, and pulse width) and seizure induction appear to work in synergy, but the&#xD;
      underlying mechanism of action for successful response has yet to be fully elucidated.&#xD;
      Moreover, further work is needed to understand the relationship between clinical improvement&#xD;
      and cognitive impairment. This investigation will examine the clinical and neurocognitive&#xD;
      impact of targeted medial temporal lobe engagement as a function of pulse amplitude, one of&#xD;
      several variable factors influencing the ECT charge. The ECT charge is measured in&#xD;
      millicoulombs (mC) and derived from multiplying pulse train duration, pulse-pair frequency,&#xD;
      pulse width, and pulse amplitude. Pulse amplitude determines the induced electric field&#xD;
      strength in the brain and is presently fixed at 900 milliamperes (mA) with no clinical or&#xD;
      scientific justification. The central hypothesis of this investigation is that the optimal&#xD;
      pulse amplitude for an individual patient will enhance neuroplasticity (clinical response)&#xD;
      while minimizing the disruption of dominant hemisphere hippocampal cognitive circuitry&#xD;
      (resulting in cognitive stability). The preliminary data informs the dosage range between 600&#xD;
      and 800 mA. Pulse amplitudes outside of this range compromise efficacy (500 mA) or may&#xD;
      increase risk of cognitive impairment (900 mA). The first aim of this investigation will&#xD;
      identify the electric field strength and neuroplasticity associated with clinical response.&#xD;
      Critically, this aim will establish the neuroplasticity threshold, which is defined as the&#xD;
      electric field strength necessary to induce neuroplasticity. The second aim will detect the&#xD;
      neural correlates of ECT-mediated cognitive changes, which may be related to disrupted&#xD;
      dominant hemisphere long-term potentiation. The third aim will use data-driven dual&#xD;
      regression to predict the optimal pulse amplitude for an individual patient. This&#xD;
      contribution will be significant because the electric field, when manipulated by pulse&#xD;
      amplitude, can subsequently maximize hippocampal neuroplasticity (efficacy) and minimize&#xD;
      disrupted connectivity (cognitive stability) thus improving clinical outcomes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2016</start_date>
  <completion_date type="Actual">March 23, 2020</completion_date>
  <primary_completion_date type="Actual">March 23, 2020</primary_completion_date>
  <phase>Phase 4</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>
    <intervention_model_description>Subjects randomized to right unilateral ECT with 600, 700, or 800 mA pulse amplitude.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
    <masking_description>Double-blind (participant and outcomes assessor)</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Depression Severity</measure>
    <time_frame>post-ECT Hamilton Depression Rating Scale -24 item. The time frame is 4 weeks after study initiation.</time_frame>
    <description>Hamilton Depression Rating Scale - 24 item. Scores range from 0 to 76 (higher scores indicate more depression severity)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cognition</measure>
    <time_frame>post-ECT Hopkins Verbal Learning Trial-Revised (percent retention score, range 0 - 100, higher is better). The time frame is 4 weeks after study initiation.</time_frame>
    <description>Hopkins Verbal Learning Trial-Revised (percent retention score, range 0 - 100, higher is better)</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">62</enrollment>
  <condition>Major Depressive Disorder</condition>
  <arm_group>
    <arm_group_label>600 mA Right Unilateral ECT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MECTA Spectrum 5000Q Amplitude</description>
  </arm_group>
  <arm_group>
    <arm_group_label>700 mA Right Unilateral ECT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MECTA Spectrum 5000Q Amplitude</description>
  </arm_group>
  <arm_group>
    <arm_group_label>800 mA Right Unilateral ECT</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>MECTA Spectrum 5000Q Amplitude</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>MECTA Spectrum 5000Q Amplitude</intervention_name>
    <description>Current</description>
    <arm_group_label>600 mA Right Unilateral ECT</arm_group_label>
    <arm_group_label>700 mA Right Unilateral ECT</arm_group_label>
    <arm_group_label>800 mA Right Unilateral ECT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Diagnosis of major depressive disorder (with or without psychotic features)&#xD;
&#xD;
          2. the clinical indications for ECT including treatment resistance or a need for a rapid&#xD;
             and definitive response&#xD;
&#xD;
          3. Hamilton Depression Rating Scale 24-item (HDRS-24) &gt; 21&#xD;
&#xD;
          4. age range between 50 and 80 years of age&#xD;
&#xD;
          5. right-handedness&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Defined neurological or neurodegenerative disorder (e.g., history of head injury with&#xD;
             loss of consciousness &gt; 5 minutes, epilepsy, Alzheimer's disease)&#xD;
&#xD;
          2. other psychiatric conditions (e.g., schizophrenia, schizoaffective disorder, bipolar&#xD;
             disorder)&#xD;
&#xD;
          3. current drug or alcohol use disorder, except for nicotine; and 4) contraindications to&#xD;
             MRI.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chris Abbott, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of New Mexico</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Chris Abbott</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87131-0001</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Abbott CC, Quinn D, Miller J, Ye E, Iqbal S, Lloyd M, Jones TR, Upston J, Deng Z, Erhardt E, McClintock SM. Electroconvulsive Therapy Pulse Amplitude and Clinical Outcomes. Am J Geriatr Psychiatry. 2021 Feb;29(2):166-178. doi: 10.1016/j.jagp.2020.06.008. Epub 2020 Jun 17.</citation>
    <PMID>32651051</PMID>
  </results_reference>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>August 16, 2016</study_first_submitted>
  <study_first_submitted_qc>December 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 21, 2016</study_first_posted>
  <results_first_submitted>November 24, 2021</results_first_submitted>
  <results_first_submitted_qc>June 30, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">July 24, 2023</results_first_posted>
  <last_update_submitted>June 30, 2023</last_update_submitted>
  <last_update_submitted_qc>June 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 24, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of New Mexico</investigator_affiliation>
    <investigator_full_name>Christopher Abbott</investigator_full_name>
    <investigator_title>Medical Director ECT Service</investigator_title>
  </responsible_party>
  <keyword>electroconvulsive therapy</keyword>
  <keyword>MRI</keyword>
  <keyword>major depressive disorder</keyword>
  <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>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>National Data Archive (NDA)</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_time_frame>Clinical, cognitive and MRI data was uploaded to NDA.</ipd_time_frame>
    <ipd_access_criteria>per NDA protocol</ipd_access_criteria>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 24, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/69/NCT02999269/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>600 mA Right Unilateral ECT</title>
          <description>MECTA Spectrum 5000Q Amplitude&#xD;
MECTA Spectrum 5000Q Amplitude: Current</description>
        </group>
        <group group_id="P2">
          <title>700 mA Right Unilateral ECT</title>
          <description>MECTA Spectrum 5000Q Amplitude&#xD;
MECTA Spectrum 5000Q Amplitude: Current</description>
        </group>
        <group group_id="P3">
          <title>800 mA Right Unilateral ECT</title>
          <description>MECTA Spectrum 5000Q Amplitude&#xD;
MECTA Spectrum 5000Q Amplitude: Current</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="20"/>
                <participants group_id="P3" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="15"/>
                <participants group_id="P3" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>600 mA Right Unilateral ECT</title>
          <description>MECTA Spectrum 5000Q Amplitude&#xD;
MECTA Spectrum 5000Q Amplitude: Current</description>
        </group>
        <group group_id="B2">
          <title>700 mA Right Unilateral ECT</title>
          <description>MECTA Spectrum 5000Q Amplitude&#xD;
MECTA Spectrum 5000Q Amplitude: Current</description>
        </group>
        <group group_id="B3">
          <title>800 mA Right Unilateral ECT</title>
          <description>MECTA Spectrum 5000Q Amplitude&#xD;
MECTA Spectrum 5000Q Amplitude: Current</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="16"/>
            <count group_id="B2" value="15"/>
            <count group_id="B3" value="16"/>
            <count group_id="B4" value="47"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="24"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="65" spread="8"/>
                    <measurement group_id="B2" value="64" spread="7"/>
                    <measurement group_id="B3" value="67" spread="10"/>
                    <measurement group_id="B4" value="65" spread="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="15"/>
                    <measurement group_id="B4" value="44"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <description>Hamilton Depression Rating Scale - 24 items Clinician rated measure of depression severity, range 0 -76 with higher scores indicating more severe depression</description>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="16"/>
                    <measurement group_id="B4" value="47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Hamilton Depression Rating Scale 24 items</title>
          <description>Clinician rated scale obtained during structured interview with subject. The scoring range is from 0 to 76 with higher scores indicating more depression severity</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="37.0" spread="7.8"/>
                    <measurement group_id="B2" value="38.0" spread="7.5"/>
                    <measurement group_id="B3" value="33.8" spread="6.7"/>
                    <measurement group_id="B4" value="36.3" spread="7.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Depression Severity</title>
        <description>Hamilton Depression Rating Scale - 24 item. Scores range from 0 to 76 (higher scores indicate more depression severity)</description>
        <time_frame>post-ECT Hamilton Depression Rating Scale -24 item. The time frame is 4 weeks after study initiation.</time_frame>
        <population>full longitudinal model with an unstructured repeated measures covariance matrix</population>
        <group_list>
          <group group_id="O1">
            <title>600 mA Right Unilateral ECT</title>
            <description>MECTA Spectrum 5000Q Amplitude&#xD;
MECTA Spectrum 5000Q Amplitude: Current</description>
          </group>
          <group group_id="O2">
            <title>700 mA Right Unilateral ECT</title>
            <description>MECTA Spectrum 5000Q Amplitude&#xD;
MECTA Spectrum 5000Q Amplitude: Current</description>
          </group>
          <group group_id="O3">
            <title>800 mA Right Unilateral ECT</title>
            <description>MECTA Spectrum 5000Q Amplitude&#xD;
MECTA Spectrum 5000Q Amplitude: Current</description>
          </group>
        </group_list>
        <measure>
          <title>Depression Severity</title>
          <description>Hamilton Depression Rating Scale - 24 item. Scores range from 0 to 76 (higher scores indicate more depression severity)</description>
          <population>full longitudinal model with an unstructured repeated measures covariance matrix</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.5" spread="2.3"/>
                    <measurement group_id="O2" value="12.0" spread="2.1"/>
                    <measurement group_id="O3" value="14.1" spread="2.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>For the primary outcomes (change in HDRS24), we performed a full longitudinal model with an unstructured repeated measures covariance matrix on subjects who completed the study in the assigned treatment arm. The dependent variable was HDRS at each visit and the independent variables included progress (time within the ECT series: pre-, mid-, and post-ECT), amplitude, age, sex, pulse width and the following interactions: progress/amplitude, progress/sex, and progress/pulse width.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.04</p_value>
            <p_value_desc>p-value for time by amplitude interaction</p_value_desc>
            <method>Regression, Linear</method>
            <other_analysis_desc>Time-by-amplitude interaction (F4, 72 = 2.65, p = 0.04).</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0001</p_value>
            <method>Regression, Linear</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Cognition</title>
        <description>Hopkins Verbal Learning Trial-Revised (percent retention score, range 0 - 100, higher is better)</description>
        <time_frame>post-ECT Hopkins Verbal Learning Trial-Revised (percent retention score, range 0 - 100, higher is better). The time frame is 4 weeks after study initiation.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>600 mA Right Unilateral ECT</title>
            <description>MECTA Spectrum 5000Q Amplitude&#xD;
MECTA Spectrum 5000Q Amplitude: Current</description>
          </group>
          <group group_id="O2">
            <title>700 mA Right Unilateral ECT</title>
            <description>MECTA Spectrum 5000Q Amplitude&#xD;
MECTA Spectrum 5000Q Amplitude: Current</description>
          </group>
          <group group_id="O3">
            <title>800 mA Right Unilateral ECT</title>
            <description>MECTA Spectrum 5000Q Amplitude&#xD;
MECTA Spectrum 5000Q Amplitude: Current</description>
          </group>
        </group_list>
        <measure>
          <title>Cognition</title>
          <description>Hopkins Verbal Learning Trial-Revised (percent retention score, range 0 - 100, higher is better)</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="57.3" spread="10"/>
                    <measurement group_id="O2" value="68" spread="9"/>
                    <measurement group_id="O3" value="62" spread="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.37</p_value>
            <method>Regression, Linear</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.50</p_value>
            <p_value_desc>p-value is time-by-amplitude interaction</p_value_desc>
            <method>Regression, Linear</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt; 0.01</p_value>
            <p_value_desc>Progress (F2,71 = 11.15, p &lt; 0.01)</p_value_desc>
            <method>Regression, Linear</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Each subject was evaluated for adverse effects over the 4-week study protocol.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>600 mA Right Unilateral ECT</title>
          <description>MECTA Spectrum 5000Q Amplitude&#xD;
MECTA Spectrum 5000Q Amplitude: Current</description>
        </group>
        <group group_id="E2">
          <title>700 mA Right Unilateral ECT</title>
          <description>MECTA Spectrum 5000Q Amplitude&#xD;
MECTA Spectrum 5000Q Amplitude: Current</description>
        </group>
        <group group_id="E3">
          <title>800 mA Right Unilateral ECT</title>
          <description>MECTA Spectrum 5000Q Amplitude&#xD;
MECTA Spectrum 5000Q Amplitude: Current</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="20"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>headache</sub_title>
                <description>post-procedure headache, all cases resolved with over the counter medications (Tylenol)</description>
                <counts group_id="E1" events="10" subjects_affected="5" subjects_at_risk="20"/>
                <counts group_id="E2" events="17" subjects_affected="6" subjects_at_risk="20"/>
                <counts group_id="E3" events="17" subjects_affected="6" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Subjects discontinued scheduled antidepressant and antipsychotic medications prior to the first imaging assessment, but as-needed medications (lorazepam, quetiapine, trazodone) were permissible with dose restrictions during the ECT series. Second, our study design included a change in pulse width (from 0.3 to 1.0 ms). Each amplitude arm had a very limited number of subjects with brief pulse width. The relationship between amplitude and pulse width will require more research.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Chris Abbott, Division Chief Neuromodulaton, Department of Psychiatry</name_or_title>
      <organization>University of New Mexico</organization>
      <phone>505272223</phone>
      <email>cabbott@salud.unm.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02999269
org study id: 5U01MH111826
secondary id: 5U01MH111826
nct id: NCT02999269
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
Electroconvulsive therapy (ECT) remains the gold-standard treatment for patients with
      depressive episodes. During a typical four-week ECT series, most depressive episodes will
      respond to treatment and people will improve their level of functioning (return to work or
      family). Independent of the antidepressant effect of ECT, many patients experience transient
      memory impairment. This investigation will examine the impact of one ECT parameter (pulse
      amplitude or current) on brain changes (structure of connections within the brain) and
      clinical outcomes. The goal of this investigation is to determine the optimal parameter for
      an individual patient that will maintain the clinical response (reduce depression severity)
      and minimize side effects (eliminate memory issues related to treatment).
Electroconvulsive therapy (ECT) remains the gold-standard treatment for patients with
      depressive episodes. During a typical four-week ECT series, most depressive episodes remit,
      and formerly suicidal or psychotically depressed patients will resume their premorbid levels
      of functioning. Independent of the antidepressant effect of ECT, many patients experience
      debilitating but transient cognitive effects such as attention and memory deficits. These
      unwanted side effects are particularly troubling for older patients who are more likely to
      have existing cognitive deficits. Both the stimulus delivery (electrode placement, pulse
      amplitude, and pulse width) and seizure induction appear to work in synergy, but the
      underlying mechanism of action for successful response has yet to be fully elucidated.
      Moreover, further work is needed to understand the relationship between clinical improvement
      and cognitive impairment. This investigation will examine the clinical and neurocognitive
      impact of targeted medial temporal lobe engagement as a function of pulse amplitude, one of
      several variable factors influencing the ECT charge. The ECT charge is measured in
      millicoulombs (mC) and derived from multiplying pulse train duration, pulse-pair frequency,
      pulse width, and pulse amplitude. Pulse amplitude determines the induced electric field
      strength in the brain and is presently fixed at 900 milliamperes (mA) with no clinical or
      scientific justification. The central hypothesis of this investigation is that the optimal
      pulse amplitude for an individual patient will enhance neuroplasticity (clinical response)
      while minimizing the disruption of dominant hemisphere hippocampal cognitive circuitry
      (resulting in cognitive stability). The preliminary data informs the dosage range between 600
      and 800 mA. Pulse amplitudes outside of this range compromise efficacy (500 mA) or may
      increase risk of cognitive impairment (900 mA). The first aim of this investigation will
      identify the electric field strength and neuroplasticity associated with clinical response.
      Critically, this aim will establish the neuroplasticity threshold, which is defined as the
      electric field strength necessary to induce neuroplasticity. The second aim will detect the
      neural correlates of ECT-mediated cognitive changes, which may be related to disrupted
      dominant hemisphere long-term potentiation. The third aim will use data-driven dual
      regression to predict the optimal pulse amplitude for an individual patient. This
      contribution will be significant because the electric field, when manipulated by pulse
      amplitude, can subsequently maximize hippocampal neuroplasticity (efficacy) and minimize
      disrupted connectivity (cognitive stability) thus improving clinical outcomes.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Subjects randomized to right unilateral ECT with 600, 700, or 800 mA pulse amplitude.
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
masking description: Double-blind (participant and outcomes assessor)
measure: Depression Severity
time frame: post-ECT Hamilton Depression Rating Scale -24 item. The time frame is 4 weeks after study initiation.
description: Hamilton Depression Rating Scale - 24 item. Scores range from 0 to 76 (higher scores indicate more depression severity)
measure: Cognition
time frame: post-ECT Hopkins Verbal Learning Trial-Revised (percent retention score, range 0 - 100, higher is better). The time frame is 4 weeks after study initiation.
description: Hopkins Verbal Learning Trial-Revised (percent retention score, range 0 - 100, higher is better)
arm group label: 600 mA Right Unilateral ECT
arm group type: Experimental
description: MECTA Spectrum 5000Q Amplitude
arm group label: 700 mA Right Unilateral ECT
arm group type: Experimental
description: MECTA Spectrum 5000Q Amplitude
arm group label: 800 mA Right Unilateral ECT
arm group type: Active Comparator
description: MECTA Spectrum 5000Q Amplitude
intervention type: Device
intervention name: MECTA Spectrum 5000Q Amplitude
description: Current
arm group label: 600 mA Right Unilateral ECT
arm group label: 700 mA Right Unilateral ECT
arm group label: 800 mA Right Unilateral ECT
criteria: 
gender: All
minimum age: 50 Years
maximum age: 80 Years
healthy volunteers: No
last name: Chris Abbott, MD
role: Principal Investigator
affiliation: University of New Mexico
facility: 
country: United States
citation: Abbott CC, Quinn D, Miller J, Ye E, Iqbal S, Lloyd M, Jones TR, Upston J, Deng Z, Erhardt E, McClintock SM. Electroconvulsive Therapy Pulse Amplitude and Clinical Outcomes. Am J Geriatr Psychiatry. 2021 Feb;29(2):166-178. doi: 10.1016/j.jagp.2020.06.008. Epub 2020 Jun 17.
PMID: 32651051
responsible party type: Principal Investigator
investigator affiliation: University of New Mexico
investigator full name: Christopher Abbott
investigator title: Medical Director ECT Service
mesh term: Depressive Disorder
mesh term: Depression
mesh term: Depressive Disorder, Major
sharing ipd: Yes
ipd description: National Data Archive (NDA)
ipd info type: Study Protocol
ipd time frame: Clinical, cognitive and MRI data was uploaded to NDA.
ipd access criteria: per NDA protocol
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Subjects discontinued scheduled antidepressant and antipsychotic medications prior to the first imaging assessment, but as-needed medications (lorazepam, quetiapine, trazodone) were permissible with dose restrictions during the ECT series. Second, our study design included a change in pulse width (from 0.3 to 1.0 ms). Each amplitude arm had a very limited number of subjects with brief pulse width. The relationship between amplitude and pulse width will require more research.
point of contact: 