<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/NCT04480918</url>
  </required_header>
  <id_info>
    <org_study_id>202003055</org_study_id>
    <nct_id>NCT04480918</nct_id>
  </id_info>
  <brief_title>University of Iowa Interventional Psychiatry Service Patient Registry</brief_title>
  <official_title>University of Iowa Interventional Psychiatry Service Patient Registry</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mark Niciu</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Iowa</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to examine the effects of interventional/procedural therapies&#xD;
      for treatment-resistant depression (TRD) and Obsessive-Compulsive Disorder (OCD). These&#xD;
      treatments include electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS),&#xD;
      racemic ketamine infusion and intranasal esketamine insufflation. The investigators will&#xD;
      obtain various indicators, or biomarkers, of a depressed individuals' state before, during,&#xD;
      and/or after these treatments. Such biomarkers include neurobehavioral testing, neuroimaging,&#xD;
      electroencephalography, cognitive testing, vocal recordings, epi/genetic testing, and&#xD;
      autonomic nervous system measures (i.e. &quot;fight-or-flight&quot; response). The results obtained&#xD;
      from this study may provide novel antidepressant treatment response biomarkers, with the&#xD;
      future goal of targeting a given treatment to an individual patient (&quot;personalized&#xD;
      medicine&quot;).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Treatment response biomarkers in TRD and OCD have been and will remain an active area of&#xD;
      research. Interventional treatments in psychiatry, e.g. ECT, TMS, racemic ketamine infusions&#xD;
      and intranasal esketamine insufflations, offer exciting opportunities for biomarker discovery&#xD;
      due their procedural nature (obviating concerns for treatment non-adherence in non-supervised&#xD;
      settings), more rapid-onset, and larger effect sizes than typically seen with traditional&#xD;
      antidepressant medications or evidence-based psychotherapies. Although no well-replicated TRD&#xD;
      biomarkers have been approved for standard clinical use, several potential biomarkers have&#xD;
      been investigated across multiple modalities, i.e. neuroimaging(1,2), autonomic&#xD;
      function(3,4), genetics(5-7), electroencephalography (EEG) (8,9), and computational analysis&#xD;
      of behavior or speech(10). These studies have promising early results but often insufficient&#xD;
      predictive power at the subject-level. The investigators anticipate that combinatorial,&#xD;
      multimodal biomarkers will enhance predictive power and, as a result, improve treatment&#xD;
      personalization in major depression.&#xD;
&#xD;
      The University of Iowa Interventional Psychiatry Service Patient Registry systematically&#xD;
      collects data from TRD and OCD patients undergoing procedural treatment(s) for major&#xD;
      depression. First, the investigators seek to replicate and/or extend discoveries from prior&#xD;
      investigations, e.g. TMS-induced autonomic changes as positive predictors of antidepressant&#xD;
      efficacy. The investigators will also compare and contrast differences, not only in response&#xD;
      to a given therapy, but also how individual subjects respond across different treatment&#xD;
      modalities, e.g. how does functional connectivity in the brain change in response to an&#xD;
      effective course of TMS as opposed to ECT? Such findings could inform the future development&#xD;
      of clinical guidelines; this is especially critical as some of these treatment modalities&#xD;
      have only recently been approved for TRD by the U.S. Food and Drug Administration, e.g.&#xD;
      intermittent theta burst stimulation (iTBS) and intranasal esketamine insufflation and dTMS&#xD;
      for OCD.&#xD;
&#xD;
      Next, a longitudinal database may also be valuable for future biomarker discovery and/or&#xD;
      replication in independent samples, i.e. an epigenetic signature of antidepressant treatment&#xD;
      response to an interventional modality identified by another research group. Similarly, this&#xD;
      patient registry could be valuable for collaborative research with other institutions&#xD;
      administering interventional treatments in psychiatry.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 2, 2020</start_date>
  <completion_date type="Anticipated">August 2050</completion_date>
  <primary_completion_date type="Anticipated">August 2050</primary_completion_date>
  <study_type>Observational [Patient Registry]</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>
  <target_duration>2 Months</target_duration>
  <primary_outcome>
    <measure>Montgomery-Åsberg Depression Rating Scale (MADRS) Pre-Post Change</measure>
    <time_frame>Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).</time_frame>
    <description>For patients with TRD, the MADRS will be administered. The MADRS contains 10 items, and each item is scored 0-6. These item scores are summed to create a scale score; thus, scale scores range from 0 to 60. A scale score of 0 indicates the absence of depressive symptoms, while a score of 60 indicates severe depression. The primary outcome is the mean change in total MADRS score. A decrease in the mean MADRS score indicates a decrease (or improvement) in depressive symptoms, whereas an increase in the mean MADRS score indicates an increase (or worsening) in depressive symptoms.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Yale-Brown Obsessive Compulsive Scale</measure>
    <time_frame>Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).</time_frame>
    <description>For patients with OCD, the YBOCS will be administered. Questions on the YBOCS examine the amount of time spent thinking and acting on obsessions and compulsions, how much impairment or distress is caused, and how much resistance and control the participant has over their thoughts or behavior.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical Global Impression/Severity (CGI) Pre-Post Change</measure>
    <time_frame>Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).</time_frame>
    <description>The CGI is a clinician-measured scale of 3 items: Severity of Illness (item 1), Global Improvement (item 2), and Efficacy Index (item 3). Items 1 and 2 are rated on a 7-point Likert scale (1=normal, 7=among the most extremely ill patients) with a possible response of &quot;not assessed.&quot; Item 3 is rated on a 4-point Likert scale from &quot;none&quot; to &quot;outweighs therapeutic effect.&quot; Items 1 and 3 are assessed in relation to last clinical encounter (if possible).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Generalized Anxiety Disorder, 7-item (GAD-7) Pre-Post Change</measure>
    <time_frame>Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).</time_frame>
    <description>The GAD-7 is the self-reported anxiety questionnaire which scores each of the 7 symptoms of Generalized Anxiety Disorder in the last two weeks on a 4-point scale, i.e. 0 (&quot;not at all&quot;), 1 (&quot;several days&quot;), 2 (&quot;over half the days&quot;) and 3 (&quot;nearly every day&quot;). Functional impairment is also assessed from &quot;Not difficult at all&quot; to &quot;Extremely difficult.&quot;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Montreal Cognitive Assessment (MoCA) Pre-Post Change</measure>
    <time_frame>Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).</time_frame>
    <description>The MoCA is a 30-point screening instrument for detecting cognitive dysfunction. It is used to assess the following cognitive domains: visuospatial/executive, naming, memory, attention, language, abstraction, delayed (short-term memory recall), and orientation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Health Questionnaire, 9-item (PHQ-9) Pre-Post Change</measure>
    <time_frame>Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).</time_frame>
    <description>The PHQ-9 is the self-reported depression module of the PHQ, which scores each of the 9 symptoms of a major depressive episode on a 4-point scale, i.e. 0 (&quot;not at all&quot;), 1 (&quot;several days&quot;), 2 (&quot;more than half the days&quot;) and 3 (&quot;nearly every day&quot;). Functional impairment is also assessed from &quot;Not difficult at all&quot; to &quot;Extremely difficult.&quot;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Temperament and Character Inventory (TCI) Pre-Post Change</measure>
    <time_frame>Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).</time_frame>
    <description>The TCI is a 240-item questionnaire. It operates with seven dimensions of personality traits, i.e. four so-called temperaments: Novelty Seeking (NS), Harm Avoidance (HA), Reward Dependence (RD), and Persistence (PS), and three so-called characters: Self-Directedness (SD), Cooperativeness (CO) and Self-Transcendence (ST). Each of these traits has a varying number of subscales.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Actigraphy Pre-Post Change</measure>
    <time_frame>Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).</time_frame>
    <description>The patient will be asked to continuously wear a Fitbit wristband to monitor gross motor activity, e.g. foot steps. Changes in gross motor activity throughout the day will also provide data on circadian rhythmicity (sleep-wake cycles).</description>
  </other_outcome>
  <other_outcome>
    <measure>Candidate Gene (DNA) Polymorphisms</measure>
    <time_frame>The genetic specimen will be obtained within approximately 1 week of starting treatment (likely with the baseline epigenetic sample.</time_frame>
    <description>The investigators will obtain tissue samples, e.g. blood, saliva, and/or cheek swabs, and DNA will be isolated and extracted. Data on genetic polymorphisms (differences) that have been demonstrated or hypothesized to play a functional role in major depression, e.g. the brain derived neurotrophic factor (BDNF) rs6265 (val66met) single nucleotide polymorphism, will be obtained. These genotypes (genetic data) will then be correlated with antidepressant response.</description>
  </other_outcome>
  <other_outcome>
    <measure>Electroencephalography (EEG) Pre-Post Change</measure>
    <time_frame>Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).</time_frame>
    <description>The investigators will obtain task-free (&quot;resting state&quot;) rs-EEG [detecting electrical signals in the brain] at baseline and in response to interventional treatments for treatment-resistant depression.</description>
  </other_outcome>
  <other_outcome>
    <measure>Epigenetic (Experience-Based) DNA Modifications Pre-Post Change</measure>
    <time_frame>The initial specimen will be obtained within approximately 1 week of starting treatment. The post-specimen will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).</time_frame>
    <description>The investigators will obtain tissue samples, e.g. blood, saliva, and/or cheek swabs, at baseline and in response to interventional treatments for treatment-resistant depression. DNA will be isolated and extracted. Data on epigenetic (experience-based) modifications to the DNA that have been demonstrated or hypothesized to play a functional role in major depression, e.g. global methylation changes, will be obtained. Changes in epigenetic status, e.g. global DNA methylation changes pre- and post-treatment, will then be correlated with antidepressant response.</description>
  </other_outcome>
  <other_outcome>
    <measure>Facial Expression Analysis Pre-Post Change</measure>
    <time_frame>Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).</time_frame>
    <description>Facial recognition software, FaceX (FaceX LLC) will be used to record and analysis facial features at rest and evoked by interview questions and emotionally provocative videos.</description>
  </other_outcome>
  <other_outcome>
    <measure>Galvanic Skin Response Pre-Post Change</measure>
    <time_frame>Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).</time_frame>
    <description>Galvanic skin response as a surrogate marker of autonomic reactivity will be obtained in response to the presentation of emotional stories or images.</description>
  </other_outcome>
  <other_outcome>
    <measure>Heart Rate Variability Pre-Post Change</measure>
    <time_frame>Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).</time_frame>
    <description>Heart rate variability as a surrogate marker of autonomic reactivity will be obtained in response to the presentation of emotional stories or images.</description>
  </other_outcome>
  <other_outcome>
    <measure>National Institutes of Health (NIH) Toolbox(R) Pre-Post Change</measure>
    <time_frame>Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).</time_frame>
    <description>The NIH Toolbox is a comprehensive set of neurobehavioral assessments that assess multiple neuropsychiatric domains. We will perform the cognitive and emotional batteries in this study.</description>
  </other_outcome>
  <other_outcome>
    <measure>Pupillometry Pre-Post Change</measure>
    <time_frame>Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).</time_frame>
    <description>Pupillometry (pupil diameter measurements) as a surrogate marker of autonomic reactivity will be obtained in response to the presentation of emotional stories or images.</description>
  </other_outcome>
  <other_outcome>
    <measure>Resting State Functional Magnetic Resonance Imaging (rs-fMRI) Pre-Post Change</measure>
    <time_frame>The initial imaging session will be obtained within approximately 1 week of starting treatment. The post-treatment imaging session occur as close as possible following completion of treatment course (usually 4-6 weeks later).</time_frame>
    <description>The investigators will obtain task-free (&quot;resting state&quot;) rs-fMRI [detecting blood oxygen-level dependent (BOLD) signal in the brain] at baseline and in response to interventional treatments for treatment-resistant depression.</description>
  </other_outcome>
  <other_outcome>
    <measure>Structural Magnetic Resonance Imaging (MRI) Pre-Post Change</measure>
    <time_frame>The initial imaging session will be obtained within approximately 1 week of starting treatment. The post-treatment imaging session occur as close as possible following completion of treatment course (usually 4-6 weeks later).</time_frame>
    <description>The investigators will obtain structural brain imaging at baseline and in response to interventional treatments for treatment-resistant depression.</description>
  </other_outcome>
  <other_outcome>
    <measure>Vocal Pattern Detection Pre, During and Post-Change</measure>
    <time_frame>Pre-assessment will be obtained within approximately 1 week of starting treatment. Interim assessments will occur weekly during treatment. Post-assessment will be obtained as close as possible following completion of treatment course.</time_frame>
    <description>The patient will be asked to read standardized passages, i.e. Grandfather Passage and Rainbow Passage, and answer questions about daily life and interests while being recorded. These recordings will be transcribed and analyzed for vocal tone, inflection, word choice, etc.</description>
  </other_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">1000</enrollment>
  <condition>Treatment Resistant Depression</condition>
  <condition>Major Depressive Episode</condition>
  <condition>Major Depression</condition>
  <condition>Major Depressive Disorder</condition>
  <condition>Bipolar Disorder</condition>
  <condition>Bipolar Depression</condition>
  <condition>Obsessive-Compulsive Disorder</condition>
  <arm_group>
    <arm_group_label>Major Depressive Episode</arm_group_label>
    <description>After referral to the University of Iowa's Interventional Psychiatry Clinic, the patient will be clinically evaluated and, if appropriate, commence the procedural-based treatment course.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Electroconvulsive Therapy (ECT)</intervention_name>
    <description>ECT for the treatment of treatment-resistant depression OR Bipolar Disorder in an active major depressive episode</description>
    <arm_group_label>Major Depressive Episode</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Transcranial Magnetic Stimulation (TMS)</intervention_name>
    <description>TMS for the treatment of treatment-resistant depression in an active major depressive episode</description>
    <arm_group_label>Major Depressive Episode</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketamine</intervention_name>
    <description>Intravenous ketamine infusion for the treatment of treatment-resistant depression in an active major depressive episode</description>
    <arm_group_label>Major Depressive Episode</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Esketamine</intervention_name>
    <description>Intranasal esketamine insufflation for the treatment of treatment-resistant depression in an active major depressive episode</description>
    <arm_group_label>Major Depressive Episode</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Deep Transcranial Magnetic Stimulation (dTMS)</intervention_name>
    <description>TMS for the treatment of OCD</description>
    <arm_group_label>Major Depressive Episode</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      blood, saliva and cheek swabs for epi/genetic expression&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Adult patients (18-99 years old) in a current major depressive episode in the context of&#xD;
        major depressive disorder (MDD) or bipolar disorder (BD) will be recruited for this&#xD;
        protocol. Adult patients received TMS for OCD will also be recruited. All treatment will be&#xD;
        in addition to the patient's clinical care with the University of Iowa's Interventional&#xD;
        Psychiatry Service for treatment-resistant major depression or OCD, and the decision to&#xD;
        participate, withdraw from participation or not participate will if not affect clinical&#xD;
        care decision-making. We appreciate that minority groups tend to be underrepresented in&#xD;
        neuropsychiatric research studies. Therefore, we will make a concerted effort to keep the&#xD;
        proportion of racial/ethnic minorities recruited consistent with the demographics of the&#xD;
        surrounding communities.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        INCLUSION CRITERIA:&#xD;
&#xD;
          1. 18-99 years of age&#xD;
&#xD;
          2. English-speaker with a level of understanding sufficient to agree to clinical&#xD;
             treatment with a treatment modality offered by the Interventional Psychiatry Service,&#xD;
             all required research procedures, and sign an informed consent document&#xD;
&#xD;
          3. Clinical diagnosis of a major depressive episode in the context of major depressive&#xD;
             disorder or bipolar disorder or treatment-resistant OCD evaluated by a provider on the&#xD;
             Interventional Psychiatry Service and felt to be an appropriate candidate for clinical&#xD;
             treatment with a treatment modality offered by the Interventional Psychiatry Service.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
          1. Age less than 18 years&#xD;
&#xD;
          2. A primary neuropsychiatric diagnosis that is not either major depressive disorder or&#xD;
             bipolar disorder&#xD;
&#xD;
          3. Serious, unstable medical conditions/problems including hepatic, renal,&#xD;
             gastroenterologic, respiratory, cardiovascular, endocrinologic, neurologic,&#xD;
             immunologic, or hematologic disease, e.g. uncontrolled asthma, uncontrolled&#xD;
             hyper/hypothyroidism or active cancer.&#xD;
&#xD;
          4. Involuntary commitment to psychiatry inpatient units&#xD;
&#xD;
          5. If patients have one or more of the following MRI Exclusion criteria, they will not be&#xD;
             able to participate in those aspects of this study:&#xD;
&#xD;
               1. The presence of an implanted device including pacemaker, coronary stent,&#xD;
                  defibrillator, or neurostimulation device that is not MRI-compatible&#xD;
&#xD;
               2. The presence of ferromagnetic objects in the body, i.e. bullets, shrapnel, and/or&#xD;
                  metal slivers&#xD;
&#xD;
               3. Clinically-significant claustrophobia&#xD;
&#xD;
               4. Clinically-significant hearing loss&#xD;
&#xD;
               5. Pregnant or nursing women or women of child bearing potential not using at least&#xD;
                  one medically accepted means of contraception (to include oral, injectable, or&#xD;
                  implant birth control, condom or diaphragm with spermicide, intrauterine devices&#xD;
                  (IUD), tubal ligation, abstinence, or partner with vasectomy)&#xD;
&#xD;
               6. The presence of any medical illness likely to alter brain morphology and/or&#xD;
                  physiology (e.g., hypertension, diabetes) even if controlled by medications&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mark J Niciu, M.D., Ph. D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Iowa</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Nicholas T Trapp, M.D., M.S.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Iowa</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Alexandra A Alario, B.S.</last_name>
    <phone>319-384-8470</phone>
    <email>alexandra-alario@uiowa.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Benjamin D Pace, M.S.</last_name>
    <phone>319-384-9302</phone>
    <email>benjamin-pace@uiowa.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Iowa Health Care</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Benjamin Pace, M.S.</last_name>
      <phone>319-384-9302</phone>
      <email>benjamin-pace@uiowa.edu</email>
    </contact>
    <contact_backup>
      <last_name>Alex Alario, B.S.</last_name>
      <phone>319-384-8470</phone>
      <email>alexandra-alario@uiowa.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Mark J Niciu, M.D. Ph.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Nicholas T Trapp, M.D. M.S.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Levy A, Taib S, Arbus C, Peran P, Sauvaget A, Schmitt L, Yrondi A. Neuroimaging Biomarkers at Baseline Predict Electroconvulsive Therapy Overall Clinical Response in Depression: A Systematic Review. J ECT. 2019 Jun;35(2):77-83. doi: 10.1097/YCT.0000000000000570.</citation>
    <PMID>30628993</PMID>
  </reference>
  <reference>
    <citation>Cash RFH, Cocchi L, Anderson R, Rogachov A, Kucyi A, Barnett AJ, Zalesky A, Fitzgerald PB. A multivariate neuroimaging biomarker of individual outcome to transcranial magnetic stimulation in depression. Hum Brain Mapp. 2019 Nov 1;40(16):4618-4629. doi: 10.1002/hbm.24725. Epub 2019 Jul 22.</citation>
    <PMID>31332903</PMID>
  </reference>
  <reference>
    <citation>Iseger TA, Padberg F, Kenemans JL, Gevirtz R, Arns M. Neuro-Cardiac-Guided TMS (NCG-TMS): Probing DLPFC-sgACC-vagus nerve connectivity using heart rate - First results. Brain Stimul. 2017 Sep-Oct;10(5):1006-1008. doi: 10.1016/j.brs.2017.05.002. Epub 2017 May 12.</citation>
    <PMID>28545770</PMID>
  </reference>
  <reference>
    <citation>Cabrerizo M, Cabrera A, Perez JO, de la Rua J, Rojas N, Zhou Q, Pinzon-Ardila A, Gonzalez-Arias SM, Adjouadi M. Induced effects of transcranial magnetic stimulation on the autonomic nervous system and the cardiac rhythm. ScientificWorldJournal. 2014;2014:349718. doi: 10.1155/2014/349718. Epub 2014 Jul 17.</citation>
    <PMID>25136660</PMID>
  </reference>
  <reference>
    <citation>Zarate CA Jr, Mathews DC, Furey ML. Human biomarkers of rapid antidepressant effects. Biol Psychiatry. 2013 Jun 15;73(12):1142-55. doi: 10.1016/j.biopsych.2012.11.031. Epub 2013 Jan 29.</citation>
    <PMID>23374639</PMID>
  </reference>
  <reference>
    <citation>Niciu MJ, Mathews DC, Nugent AC, Ionescu DF, Furey ML, Richards EM, Machado-Vieira R, Zarate CA Jr. Developing biomarkers in mood disorders research through the use of rapid-acting antidepressants. Depress Anxiety. 2014 Apr;31(4):297-307. doi: 10.1002/da.22224. Epub 2013 Dec 18.</citation>
    <PMID>24353110</PMID>
  </reference>
  <reference>
    <citation>Pinna M, Manchia M, Oppo R, Scano F, Pillai G, Loche AP, Salis P, Minnai GP. Clinical and biological predictors of response to electroconvulsive therapy (ECT): a review. Neurosci Lett. 2018 Mar 16;669:32-42. doi: 10.1016/j.neulet.2016.10.047. Epub 2016 Oct 25.</citation>
    <PMID>27793702</PMID>
  </reference>
  <reference>
    <citation>Kerwin LJ, Keller CJ, Wu W, Narayan M, Etkin A. Test-retest reliability of transcranial magnetic stimulation EEG evoked potentials. Brain Stimul. 2018 May-Jun;11(3):536-544. doi: 10.1016/j.brs.2017.12.010. Epub 2017 Dec 29.</citation>
    <PMID>29342443</PMID>
  </reference>
  <reference>
    <citation>Minelli A, Abate M, Zampieri E, Gainelli G, Trabucchi L, Segala M, Sartori R, Gennarelli M, Conca A, Bortolomasi M. Seizure Adequacy Markers and the Prediction of Electroconvulsive Therapy Response. J ECT. 2016 Jun;32(2):88-92. doi: 10.1097/YCT.0000000000000274.</citation>
    <PMID>26397151</PMID>
  </reference>
  <reference>
    <citation>Smith M, Dietrich BJ, Bai EW, Bockholt HJ. Vocal pattern detection of depression among older adults. Int J Ment Health Nurs. 2020 Jun;29(3):440-449. doi: 10.1111/inm.12678. Epub 2019 Dec 6.</citation>
    <PMID>31811697</PMID>
  </reference>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>July 2, 2020</study_first_submitted>
  <study_first_submitted_qc>July 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 22, 2020</study_first_posted>
  <last_update_submitted>May 8, 2023</last_update_submitted>
  <last_update_submitted_qc>May 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Iowa</investigator_affiliation>
    <investigator_full_name>Mark Niciu</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>Electroconvulsive Therapy</keyword>
  <keyword>Transcranial Magnetic Stimulation</keyword>
  <keyword>Ketamine</keyword>
  <keyword>Esketamine</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>Bipolar Disorder</mesh_term>
    <mesh_term>Obsessive-Compulsive Disorder</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>Ketamine</mesh_term>
    <mesh_term>Esketamine</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/NCT04480918
org study id: 202003055
nct id: NCT04480918
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: Yes
The purpose of this study is to examine the effects of interventional/procedural therapies
      for treatment-resistant depression (TRD) and Obsessive-Compulsive Disorder (OCD). These
      treatments include electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS),
      racemic ketamine infusion and intranasal esketamine insufflation. The investigators will
      obtain various indicators, or biomarkers, of a depressed individuals' state before, during,
      and/or after these treatments. Such biomarkers include neurobehavioral testing, neuroimaging,
      electroencephalography, cognitive testing, vocal recordings, epi/genetic testing, and
      autonomic nervous system measures (i.e. "fight-or-flight" response). The results obtained
      from this study may provide novel antidepressant treatment response biomarkers, with the
      future goal of targeting a given treatment to an individual patient ("personalized
      medicine").
Treatment response biomarkers in TRD and OCD have been and will remain an active area of
      research. Interventional treatments in psychiatry, e.g. ECT, TMS, racemic ketamine infusions
      and intranasal esketamine insufflations, offer exciting opportunities for biomarker discovery
      due their procedural nature (obviating concerns for treatment non-adherence in non-supervised
      settings), more rapid-onset, and larger effect sizes than typically seen with traditional
      antidepressant medications or evidence-based psychotherapies. Although no well-replicated TRD
      biomarkers have been approved for standard clinical use, several potential biomarkers have
      been investigated across multiple modalities, i.e. neuroimaging(1,2), autonomic
      function(3,4), genetics(5-7), electroencephalography (EEG) (8,9), and computational analysis
      of behavior or speech(10). These studies have promising early results but often insufficient
      predictive power at the subject-level. The investigators anticipate that combinatorial,
      multimodal biomarkers will enhance predictive power and, as a result, improve treatment
      personalization in major depression.

      The University of Iowa Interventional Psychiatry Service Patient Registry systematically
      collects data from TRD and OCD patients undergoing procedural treatment(s) for major
      depression. First, the investigators seek to replicate and/or extend discoveries from prior
      investigations, e.g. TMS-induced autonomic changes as positive predictors of antidepressant
      efficacy. The investigators will also compare and contrast differences, not only in response
      to a given therapy, but also how individual subjects respond across different treatment
      modalities, e.g. how does functional connectivity in the brain change in response to an
      effective course of TMS as opposed to ECT? Such findings could inform the future development
      of clinical guidelines; this is especially critical as some of these treatment modalities
      have only recently been approved for TRD by the U.S. Food and Drug Administration, e.g.
      intermittent theta burst stimulation (iTBS) and intranasal esketamine insufflation and dTMS
      for OCD.

      Next, a longitudinal database may also be valuable for future biomarker discovery and/or
      replication in independent samples, i.e. an epigenetic signature of antidepressant treatment
      response to an interventional modality identified by another research group. Similarly, this
      patient registry could be valuable for collaborative research with other institutions
      administering interventional treatments in psychiatry.
observational model: Cohort
time perspective: Prospective
measure: Montgomery-Åsberg Depression Rating Scale (MADRS) Pre-Post Change
time frame: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
description: For patients with TRD, the MADRS will be administered. The MADRS contains 10 items, and each item is scored 0-6. These item scores are summed to create a scale score; thus, scale scores range from 0 to 60. A scale score of 0 indicates the absence of depressive symptoms, while a score of 60 indicates severe depression. The primary outcome is the mean change in total MADRS score. A decrease in the mean MADRS score indicates a decrease (or improvement) in depressive symptoms, whereas an increase in the mean MADRS score indicates an increase (or worsening) in depressive symptoms.
measure: Yale-Brown Obsessive Compulsive Scale
time frame: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
description: For patients with OCD, the YBOCS will be administered. Questions on the YBOCS examine the amount of time spent thinking and acting on obsessions and compulsions, how much impairment or distress is caused, and how much resistance and control the participant has over their thoughts or behavior.
measure: Clinical Global Impression/Severity (CGI) Pre-Post Change
time frame: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
description: The CGI is a clinician-measured scale of 3 items: Severity of Illness (item 1), Global Improvement (item 2), and Efficacy Index (item 3). Items 1 and 2 are rated on a 7-point Likert scale (1=normal, 7=among the most extremely ill patients) with a possible response of "not assessed." Item 3 is rated on a 4-point Likert scale from "none" to "outweighs therapeutic effect." Items 1 and 3 are assessed in relation to last clinical encounter (if possible).
measure: Generalized Anxiety Disorder, 7-item (GAD-7) Pre-Post Change
time frame: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
description: The GAD-7 is the self-reported anxiety questionnaire which scores each of the 7 symptoms of Generalized Anxiety Disorder in the last two weeks on a 4-point scale, i.e. 0 ("not at all"), 1 ("several days"), 2 ("over half the days") and 3 ("nearly every day"). Functional impairment is also assessed from "Not difficult at all" to "Extremely difficult."
measure: Montreal Cognitive Assessment (MoCA) Pre-Post Change
time frame: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
description: The MoCA is a 30-point screening instrument for detecting cognitive dysfunction. It is used to assess the following cognitive domains: visuospatial/executive, naming, memory, attention, language, abstraction, delayed (short-term memory recall), and orientation.
measure: Patient Health Questionnaire, 9-item (PHQ-9) Pre-Post Change
time frame: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
description: The PHQ-9 is the self-reported depression module of the PHQ, which scores each of the 9 symptoms of a major depressive episode on a 4-point scale, i.e. 0 ("not at all"), 1 ("several days"), 2 ("more than half the days") and 3 ("nearly every day"). Functional impairment is also assessed from "Not difficult at all" to "Extremely difficult."
measure: Temperament and Character Inventory (TCI) Pre-Post Change
time frame: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
description: The TCI is a 240-item questionnaire. It operates with seven dimensions of personality traits, i.e. four so-called temperaments: Novelty Seeking (NS), Harm Avoidance (HA), Reward Dependence (RD), and Persistence (PS), and three so-called characters: Self-Directedness (SD), Cooperativeness (CO) and Self-Transcendence (ST). Each of these traits has a varying number of subscales.
measure: Actigraphy Pre-Post Change
time frame: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
description: The patient will be asked to continuously wear a Fitbit wristband to monitor gross motor activity, e.g. foot steps. Changes in gross motor activity throughout the day will also provide data on circadian rhythmicity (sleep-wake cycles).
measure: Candidate Gene (DNA) Polymorphisms
time frame: The genetic specimen will be obtained within approximately 1 week of starting treatment (likely with the baseline epigenetic sample.
description: The investigators will obtain tissue samples, e.g. blood, saliva, and/or cheek swabs, and DNA will be isolated and extracted. Data on genetic polymorphisms (differences) that have been demonstrated or hypothesized to play a functional role in major depression, e.g. the brain derived neurotrophic factor (BDNF) rs6265 (val66met) single nucleotide polymorphism, will be obtained. These genotypes (genetic data) will then be correlated with antidepressant response.
measure: Electroencephalography (EEG) Pre-Post Change
time frame: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
description: The investigators will obtain task-free ("resting state") rs-EEG [detecting electrical signals in the brain] at baseline and in response to interventional treatments for treatment-resistant depression.
measure: Epigenetic (Experience-Based) DNA Modifications Pre-Post Change
time frame: The initial specimen will be obtained within approximately 1 week of starting treatment. The post-specimen will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
description: The investigators will obtain tissue samples, e.g. blood, saliva, and/or cheek swabs, at baseline and in response to interventional treatments for treatment-resistant depression. DNA will be isolated and extracted. Data on epigenetic (experience-based) modifications to the DNA that have been demonstrated or hypothesized to play a functional role in major depression, e.g. global methylation changes, will be obtained. Changes in epigenetic status, e.g. global DNA methylation changes pre- and post-treatment, will then be correlated with antidepressant response.
measure: Facial Expression Analysis Pre-Post Change
time frame: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
description: Facial recognition software, FaceX (FaceX LLC) will be used to record and analysis facial features at rest and evoked by interview questions and emotionally provocative videos.
measure: Galvanic Skin Response Pre-Post Change
time frame: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
description: Galvanic skin response as a surrogate marker of autonomic reactivity will be obtained in response to the presentation of emotional stories or images.
measure: Heart Rate Variability Pre-Post Change
time frame: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
description: Heart rate variability as a surrogate marker of autonomic reactivity will be obtained in response to the presentation of emotional stories or images.
measure: National Institutes of Health (NIH) Toolbox(R) Pre-Post Change
time frame: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
description: The NIH Toolbox is a comprehensive set of neurobehavioral assessments that assess multiple neuropsychiatric domains. We will perform the cognitive and emotional batteries in this study.
measure: Pupillometry Pre-Post Change
time frame: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
description: Pupillometry (pupil diameter measurements) as a surrogate marker of autonomic reactivity will be obtained in response to the presentation of emotional stories or images.
measure: Resting State Functional Magnetic Resonance Imaging (rs-fMRI) Pre-Post Change
time frame: The initial imaging session will be obtained within approximately 1 week of starting treatment. The post-treatment imaging session occur as close as possible following completion of treatment course (usually 4-6 weeks later).
description: The investigators will obtain task-free ("resting state") rs-fMRI [detecting blood oxygen-level dependent (BOLD) signal in the brain] at baseline and in response to interventional treatments for treatment-resistant depression.
measure: Structural Magnetic Resonance Imaging (MRI) Pre-Post Change
time frame: The initial imaging session will be obtained within approximately 1 week of starting treatment. The post-treatment imaging session occur as close as possible following completion of treatment course (usually 4-6 weeks later).
description: The investigators will obtain structural brain imaging at baseline and in response to interventional treatments for treatment-resistant depression.
measure: Vocal Pattern Detection Pre, During and Post-Change
time frame: Pre-assessment will be obtained within approximately 1 week of starting treatment. Interim assessments will occur weekly during treatment. Post-assessment will be obtained as close as possible following completion of treatment course.
description: The patient will be asked to read standardized passages, i.e. Grandfather Passage and Rainbow Passage, and answer questions about daily life and interests while being recorded. These recordings will be transcribed and analyzed for vocal tone, inflection, word choice, etc.
arm group label: Major Depressive Episode
description: After referral to the University of Iowa's Interventional Psychiatry Clinic, the patient will be clinically evaluated and, if appropriate, commence the procedural-based treatment course.
intervention type: Device
intervention name: Electroconvulsive Therapy (ECT)
description: ECT for the treatment of treatment-resistant depression OR Bipolar Disorder in an active major depressive episode
arm group label: Major Depressive Episode
intervention type: Device
intervention name: Transcranial Magnetic Stimulation (TMS)
description: TMS for the treatment of treatment-resistant depression in an active major depressive episode
arm group label: Major Depressive Episode
intervention type: Drug
intervention name: Ketamine
description: Intravenous ketamine infusion for the treatment of treatment-resistant depression in an active major depressive episode
arm group label: Major Depressive Episode
intervention type: Drug
intervention name: Esketamine
description: Intranasal esketamine insufflation for the treatment of treatment-resistant depression in an active major depressive episode
arm group label: Major Depressive Episode
intervention type: Device
intervention name: Deep Transcranial Magnetic Stimulation (dTMS)
description: TMS for the treatment of OCD
arm group label: Major Depressive Episode
blood, saliva and cheek swabs for epi/genetic expression
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Mark J Niciu, M.D., Ph. D.
role: Principal Investigator
affiliation: University of Iowa
last name: Nicholas T Trapp, M.D., M.S.
role: Principal Investigator
affiliation: University of Iowa
last name: Alexandra A Alario, B.S.
phone: 319-384-8470
email: alexandra-alario@uiowa.edu
last name: Benjamin D Pace, M.S.
phone: 319-384-9302
email: benjamin-pace@uiowa.edu
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
country: United States
citation: Levy A, Taib S, Arbus C, Peran P, Sauvaget A, Schmitt L, Yrondi A. Neuroimaging Biomarkers at Baseline Predict Electroconvulsive Therapy Overall Clinical Response in Depression: A Systematic Review. J ECT. 2019 Jun;35(2):77-83. doi: 10.1097/YCT.0000000000000570.
PMID: 30628993
citation: Cash RFH, Cocchi L, Anderson R, Rogachov A, Kucyi A, Barnett AJ, Zalesky A, Fitzgerald PB. A multivariate neuroimaging biomarker of individual outcome to transcranial magnetic stimulation in depression. Hum Brain Mapp. 2019 Nov 1;40(16):4618-4629. doi: 10.1002/hbm.24725. Epub 2019 Jul 22.
PMID: 31332903
citation: Iseger TA, Padberg F, Kenemans JL, Gevirtz R, Arns M. Neuro-Cardiac-Guided TMS (NCG-TMS): Probing DLPFC-sgACC-vagus nerve connectivity using heart rate - First results. Brain Stimul. 2017 Sep-Oct;10(5):1006-1008. doi: 10.1016/j.brs.2017.05.002. Epub 2017 May 12.
PMID: 28545770
citation: Cabrerizo M, Cabrera A, Perez JO, de la Rua J, Rojas N, Zhou Q, Pinzon-Ardila A, Gonzalez-Arias SM, Adjouadi M. Induced effects of transcranial magnetic stimulation on the autonomic nervous system and the cardiac rhythm. ScientificWorldJournal. 2014;2014:349718. doi: 10.1155/2014/349718. Epub 2014 Jul 17.
PMID: 25136660
citation: Zarate CA Jr, Mathews DC, Furey ML. Human biomarkers of rapid antidepressant effects. Biol Psychiatry. 2013 Jun 15;73(12):1142-55. doi: 10.1016/j.biopsych.2012.11.031. Epub 2013 Jan 29.
PMID: 23374639
citation: Niciu MJ, Mathews DC, Nugent AC, Ionescu DF, Furey ML, Richards EM, Machado-Vieira R, Zarate CA Jr. Developing biomarkers in mood disorders research through the use of rapid-acting antidepressants. Depress Anxiety. 2014 Apr;31(4):297-307. doi: 10.1002/da.22224. Epub 2013 Dec 18.
PMID: 24353110
citation: Pinna M, Manchia M, Oppo R, Scano F, Pillai G, Loche AP, Salis P, Minnai GP. Clinical and biological predictors of response to electroconvulsive therapy (ECT): a review. Neurosci Lett. 2018 Mar 16;669:32-42. doi: 10.1016/j.neulet.2016.10.047. Epub 2016 Oct 25.
PMID: 27793702
citation: Kerwin LJ, Keller CJ, Wu W, Narayan M, Etkin A. Test-retest reliability of transcranial magnetic stimulation EEG evoked potentials. Brain Stimul. 2018 May-Jun;11(3):536-544. doi: 10.1016/j.brs.2017.12.010. Epub 2017 Dec 29.
PMID: 29342443
citation: Minelli A, Abate M, Zampieri E, Gainelli G, Trabucchi L, Segala M, Sartori R, Gennarelli M, Conca A, Bortolomasi M. Seizure Adequacy Markers and the Prediction of Electroconvulsive Therapy Response. J ECT. 2016 Jun;32(2):88-92. doi: 10.1097/YCT.0000000000000274.
PMID: 26397151
citation: Smith M, Dietrich BJ, Bai EW, Bockholt HJ. Vocal pattern detection of depression among older adults. Int J Ment Health Nurs. 2020 Jun;29(3):440-449. doi: 10.1111/inm.12678. Epub 2019 Dec 6.
PMID: 31811697
responsible party type: Sponsor-Investigator
investigator affiliation: University of Iowa
investigator full name: Mark Niciu
investigator title: Assistant Professor
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Major
mesh term: Bipolar Disorder
mesh term: Obsessive-Compulsive Disorder
mesh term: Depressive Disorder, Treatment-Resistant
mesh term: Ketamine
mesh term: Esketamine
sharing ipd: No