xml: <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/NCT05965739</url>
    </required_header>
    <id_info>
      <org_study_id>Pro00112477_A</org_study_id>
      <secondary_id>OTA-21-015G</secondary_id>
      <nct_id>NCT05965739</nct_id>
    </id_info>
    <brief_title>RECOVER-NEURO: Platform Protocol, Appendix_A to Measure the Effects of BrainHQ, PASC CoRE and tDCS Interventions on Long COVID Symptoms</brief_title>
    <official_title>RECOVER-NEURO: A Platform Protocol for Evaluation of Interventions for Cognitive Dysfunction in Post-Acute Sequelae of SARS-CoV-2 Infection (PASC)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Duke University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Duke University</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        This platform protocol is designed to be flexible so that it is suitable for a wide range of&#xD;
        settings within health care systems, for remote settings, and in community settings where it&#xD;
        can be integrated into COVID-19 programs and subsequent treatment plans.&#xD;
  &#xD;
        This protocol is a prospective, multi-center, multi-arm, randomized, controlled platform&#xD;
        trial evaluating potential interventions for PASC-mediated cognitive dysfunction. The&#xD;
        hypothesis is that PASC-mediated declines in cognitive domains, such as executive function&#xD;
        and attention, may be improved by interventions that selectively focus on enhancing those&#xD;
        domains.&#xD;
  &#xD;
        This design seeks to evaluate each intervention relative to the Active Comparator. The&#xD;
        BrainHQ (alone) arm is important because the intervention is commercially available,&#xD;
        accessible, relatively inexpensive, and does not require trained personnel to administer.&#xD;
        BrainHQ has been also been proven effective in other studies of cognitive dysfunction such as&#xD;
        studies in aging, mild cognitive impairment, traumatic brain injury, among others. The&#xD;
        BrainHQ + PASC CoRE arm and the BrainHQ + tDCS arms are suspected to provide cognitive&#xD;
        improvements beyond BrainHQ alone through different mechanisms. Both PASC CoRE and tDCS have&#xD;
        extensive prior use and have demonstrated utility in improving aspects of cognitive function&#xD;
        in other clinical settings..&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Participants will be randomized to one of the intervention appendices that are actively&#xD;
        enrolling at the time of randomization. Intervention appendices may be added or removed&#xD;
        according to adaptive design and/or emerging evidence. Various interventions will be studied.&#xD;
  &#xD;
        Participants will be randomized equally across the five arms:&#xD;
  &#xD;
          1. Active Comparator (video games)&#xD;
  &#xD;
          2. BrainHQ&#xD;
  &#xD;
          3. BrainHQ + PASC CoRE&#xD;
  &#xD;
          4. BrainHQ + tDCS-active&#xD;
  &#xD;
          5. BrainHQ + tDCS-sham&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Enrolling by invitation</overall_status>
    <start_date type="Actual">September 1, 2023</start_date>
    <completion_date type="Anticipated">December 2024</completion_date>
    <primary_completion_date type="Anticipated">October 2024</primary_completion_date>
    <phase>N/A</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>To achieve blinding and an equitable randomization probability, a two-step randomization process will be used. The study will employ a simple (unstratified) randomization scheme.&#xD;
  At the first stage, each participant will be assigned with equal probability to one of the intervention appendices for which the participant is eligible, after applying any intervention-specific safety exclusions. At the second stage, each participant will be assigned according to the specific appendix's randomization procedure. Participants will have an equal chance of being randomized into any of the intervention groups.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Triple (Participant, Care Provider, Investigator)</masking>
      <masking_description>Participants assigned to control will be considered part of pooled analyses if the intervention was active at the time of their enrollment and the participants were eligible to receive that intervention. This will result in approximately a 1:1 allocation ratio for any intervention to pooled control.&#xD;
  Sites will be informed to which intervention appendix participants are randomized, but, when applicable, not whether the participants are allocated to the active intervention arm or control arm within that appendix. The participants and investigators will be blinded throughout the study, when possible.&#xD;
  If open intervention appendices do not have the ability to pool controls but have independent controls, at the second stage participants will be randomized in a 1:1 ratio to intervention vs control inside the specific intervention appendix the participants were randomized to at the first stage of the randomization procedure.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Change in Everyday Cognition 2 (ECog2)</measure>
      <time_frame>Baseline to End of Intervention (EOI) (Day 70)</time_frame>
      <description>Everyday Cognition 2 (ECog2) is a self-report, 41-item questionnaire used to measure the participant's simple reaction time; respond when X happens and Choice reaction time; respond only if X happens.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change in PROMIS-cognitive function - short form 8a (PROMIS-Cog) total score</measure>
      <time_frame>Baseline, EOI (Day 70), End of Study (EOS) (Day 160)</time_frame>
      <description>The PROMIS-Cog is the PROMIS short form for the cognitive function domain and is a self-report, 8-item questionnaire targeting cognitive function in the past seven days.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change on an objective neurocognitive battery scores</measure>
      <time_frame>Baseline, EOI (Day 70), EOS (Day 160)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Everyday Cognition 2 (ECog2)</measure>
      <time_frame>Baseline, EOS (Day 160)</time_frame>
      <description>Everyday Cognition 2 (ECog2) is a self-report, 41-item questionnaire used to measure the participant's simple reaction time; respond when X happens and Choice reaction time; respond only if X happens.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Characterize the intervention's safety as measured by the proportion of Serious Adverse Events</measure>
      <time_frame>Baseline to EOS (Day 160)</time_frame>
    </secondary_outcome>
    <number_of_arms>5</number_of_arms>
    <enrollment type="Anticipated">315</enrollment>
    <condition>Long COVID</condition>
    <condition>Long Covid19</condition>
    <condition>Long Covid-19</condition>
    <arm_group>
      <arm_group_label>BrainHQ Active Comparator</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>5 sessions/week at 30 min/session</description>
    </arm_group>
    <arm_group>
      <arm_group_label>BrainHQ</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>5 sessions/week at 30 min/session</description>
    </arm_group>
    <arm_group>
      <arm_group_label>BrainHQ + PASC CoRE</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>BrainHQ plus 9 group sessions at 1.5 hr/session and 3 individual sessions at 1 hr/session</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Brain HQ + tDCS-active</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>2.0 mA stimulation delivered for 30 min during each BrainHQ session</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Brain HQ + tDCS-sham</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Inactive stimulation delivered for 30 min during each BrainHQ session</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>BrainHQ/Active Comparator Activity</intervention_name>
      <description>BrainHQ platform provides a set of cognitive activities, like puzzles and games, that are cognitively stimulating and actively engage participants but do not continuously and adaptively challenge them. These activities are designed to be a face-valid, active comparison approach to cognitive therapy, thus participants are blinded, attention time is matched, and overall user experience is identical to the active arms.</description>
      <arm_group_label>BrainHQ Active Comparator</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>BrainHQ</intervention_name>
      <description>BrainHQ is an online cognitive training program, and has been used to improve cognitive function among persons with cognitive impairment based on principles of neuroplasticity.</description>
      <arm_group_label>Brain HQ + tDCS-active</arm_group_label>
      <arm_group_label>Brain HQ + tDCS-sham</arm_group_label>
      <arm_group_label>BrainHQ</arm_group_label>
      <arm_group_label>BrainHQ + PASC CoRE</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>PASC CoRE</intervention_name>
      <description>PASC CoRE is a manualized, adaptable cognitive rehabilitation intervention with demonstrated efficacy in improving attention and executive functions, among other cognitive domains.</description>
      <arm_group_label>BrainHQ + PASC CoRE</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>tDCS-active</intervention_name>
      <description>Transcranial direct current stimulation (tDCS) will use a device specifically for home-based use. This device delivers a weak electrical current of 2.0 mA passed through two electrodes placed on the scalp to target the dorsolateral prefrontal cortex region of the brain. The electrodes are single-use for each session and can be attached to a headset by snapping into place.&#xD;
  The device has a user-friendly interface and a large-button keypad, making it is easy to use at home.</description>
      <arm_group_label>Brain HQ + tDCS-active</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>tDCS-sham</intervention_name>
      <description>tDCS devices used in the sham arm will be pre-programmed to deliver the same ramp up/down at the beginning/end of the 30-minute period as the active arm, except with no current otherwise delivered during the session.</description>
      <arm_group_label>Brain HQ + tDCS-sham</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          1. See NCT05965752 for RECOVER-NEURO: Platform Protocol level inclusion criteria which&#xD;
          applies to this appendix&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          1. See NCT05965752 for RECOVER-NEURO: Platform Protocol level exclusion criteria which&#xD;
          applies to this appendix&#xD;
  &#xD;
          Additional Appendix (Sub-study) Level Exclusion Criteria:&#xD;
  &#xD;
            1. Presence of metal objects in the head or neck&#xD;
  &#xD;
            2. Skin disorders or skin-sensitive areas near tDCS stimulation locations that would&#xD;
               interfere with electrode placement or increase the risk of stimulation-induced damage,&#xD;
               at the investigator's discretion&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Kanecia Zimmerman, MD PhD</last_name>
      <role>Study Chair</role>
      <affiliation>Duke University</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Daniel Laskowitz, MD MHS</last_name>
      <role>Study Chair</role>
      <affiliation>Duke University</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>All sites listed under NCT05965752</name>
        <address>
          <city>Durham</city>
          <state>North Carolina</state>
          <zip>27710</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <link>
      <url>http://recovercovid.org/</url>
      <description>Related Info</description>
    </link>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 25, 2023</study_first_submitted>
    <study_first_submitted_qc>July 25, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 28, 2023</study_first_posted>
    <last_update_submitted>September 6, 2023</last_update_submitted>
    <last_update_submitted_qc>September 6, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 7, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>PASC</keyword>
    <keyword>Cognitive</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>COVID-19</mesh_term>
      <mesh_term>Post-Acute COVID-19 Syndrome</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>The investigators will share the summary of results on the study website: https://recovercovid.org/</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05965739
  org study id: Pro00112477_A
  secondary id: OTA-21-015G
  nct id: NCT05965739
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  This platform protocol is designed to be flexible so that it is suitable for a wide range of
        settings within health care systems, for remote settings, and in community settings where it
        can be integrated into COVID-19 programs and subsequent treatment plans.
  
        This protocol is a prospective, multi-center, multi-arm, randomized, controlled platform
        trial evaluating potential interventions for PASC-mediated cognitive dysfunction. The
        hypothesis is that PASC-mediated declines in cognitive domains, such as executive function
        and attention, may be improved by interventions that selectively focus on enhancing those
        domains.
  
        This design seeks to evaluate each intervention relative to the Active Comparator. The
        BrainHQ (alone) arm is important because the intervention is commercially available,
        accessible, relatively inexpensive, and does not require trained personnel to administer.
        BrainHQ has been also been proven effective in other studies of cognitive dysfunction such as
        studies in aging, mild cognitive impairment, traumatic brain injury, among others. The
        BrainHQ + PASC CoRE arm and the BrainHQ + tDCS arms are suspected to provide cognitive
        improvements beyond BrainHQ alone through different mechanisms. Both PASC CoRE and tDCS have
        extensive prior use and have demonstrated utility in improving aspects of cognitive function
        in other clinical settings..
  Participants will be randomized to one of the intervention appendices that are actively
        enrolling at the time of randomization. Intervention appendices may be added or removed
        according to adaptive design and/or emerging evidence. Various interventions will be studied.
  
        Participants will be randomized equally across the five arms:
  
          1. Active Comparator (video games)
  
          2. BrainHQ
  
          3. BrainHQ + PASC CoRE
  
          4. BrainHQ + tDCS-active
  
          5. BrainHQ + tDCS-sham
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: To achieve blinding and an equitable randomization probability, a two-step randomization process will be used. The study will employ a simple (unstratified) randomization scheme.
  At the first stage, each participant will be assigned with equal probability to one of the intervention appendices for which the participant is eligible, after applying any intervention-specific safety exclusions. At the second stage, each participant will be assigned according to the specific appendix's randomization procedure. Participants will have an equal chance of being randomized into any of the intervention groups.
  primary purpose: Treatment
  masking: Triple (Participant, Care Provider, Investigator)
  masking description: Participants assigned to control will be considered part of pooled analyses if the intervention was active at the time of their enrollment and the participants were eligible to receive that intervention. This will result in approximately a 1:1 allocation ratio for any intervention to pooled control.
  Sites will be informed to which intervention appendix participants are randomized, but, when applicable, not whether the participants are allocated to the active intervention arm or control arm within that appendix. The participants and investigators will be blinded throughout the study, when possible.
  If open intervention appendices do not have the ability to pool controls but have independent controls, at the second stage participants will be randomized in a 1:1 ratio to intervention vs control inside the specific intervention appendix the participants were randomized to at the first stage of the randomization procedure.
  measure: Change in Everyday Cognition 2 (ECog2)
  time frame: Baseline to End of Intervention (EOI) (Day 70)
  description: Everyday Cognition 2 (ECog2) is a self-report, 41-item questionnaire used to measure the participant's simple reaction time; respond when X happens and Choice reaction time; respond only if X happens.
  measure: Change in PROMIS-cognitive function - short form 8a (PROMIS-Cog) total score
  time frame: Baseline, EOI (Day 70), End of Study (EOS) (Day 160)
  description: The PROMIS-Cog is the PROMIS short form for the cognitive function domain and is a self-report, 8-item questionnaire targeting cognitive function in the past seven days.
  measure: Change on an objective neurocognitive battery scores
  time frame: Baseline, EOI (Day 70), EOS (Day 160)
  measure: Change in Everyday Cognition 2 (ECog2)
  time frame: Baseline, EOS (Day 160)
  description: Everyday Cognition 2 (ECog2) is a self-report, 41-item questionnaire used to measure the participant's simple reaction time; respond when X happens and Choice reaction time; respond only if X happens.
  measure: Characterize the intervention's safety as measured by the proportion of Serious Adverse Events
  time frame: Baseline to EOS (Day 160)
  arm group label: BrainHQ Active Comparator
  arm group type: Active Comparator
  description: 5 sessions/week at 30 min/session
  arm group label: BrainHQ
  arm group type: Experimental
  description: 5 sessions/week at 30 min/session
  arm group label: BrainHQ + PASC CoRE
  arm group type: Experimental
  description: BrainHQ plus 9 group sessions at 1.5 hr/session and 3 individual sessions at 1 hr/session
  arm group label: Brain HQ + tDCS-active
  arm group type: Experimental
  description: 2.0 mA stimulation delivered for 30 min during each BrainHQ session
  arm group label: Brain HQ + tDCS-sham
  arm group type: Placebo Comparator
  description: Inactive stimulation delivered for 30 min during each BrainHQ session
  intervention type: Other
  intervention name: BrainHQ/Active Comparator Activity
  description: BrainHQ platform provides a set of cognitive activities, like puzzles and games, that are cognitively stimulating and actively engage participants but do not continuously and adaptively challenge them. These activities are designed to be a face-valid, active comparison approach to cognitive therapy, thus participants are blinded, attention time is matched, and overall user experience is identical to the active arms.
  arm group label: BrainHQ Active Comparator
  intervention type: Other
  intervention name: BrainHQ
  description: BrainHQ is an online cognitive training program, and has been used to improve cognitive function among persons with cognitive impairment based on principles of neuroplasticity.
  arm group label: Brain HQ + tDCS-active
  arm group label: Brain HQ + tDCS-sham
  arm group label: BrainHQ
  arm group label: BrainHQ + PASC CoRE
  intervention type: Other
  intervention name: PASC CoRE
  description: PASC CoRE is a manualized, adaptable cognitive rehabilitation intervention with demonstrated efficacy in improving attention and executive functions, among other cognitive domains.
  arm group label: BrainHQ + PASC CoRE
  intervention type: Device
  intervention name: tDCS-active
  description: Transcranial direct current stimulation (tDCS) will use a device specifically for home-based use. This device delivers a weak electrical current of 2.0 mA passed through two electrodes placed on the scalp to target the dorsolateral prefrontal cortex region of the brain. The electrodes are single-use for each session and can be attached to a headset by snapping into place.
  The device has a user-friendly interface and a large-button keypad, making it is easy to use at home.
  arm group label: Brain HQ + tDCS-active
  intervention type: Device
  intervention name: tDCS-sham
  description: tDCS devices used in the sham arm will be pre-programmed to deliver the same ramp up/down at the beginning/end of the 30-minute period as the active arm, except with no current otherwise delivered during the session.
  arm group label: Brain HQ + tDCS-sham
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Kanecia Zimmerman, MD PhD
  role: Study Chair
  affiliation: Duke University
  last name: Daniel Laskowitz, MD MHS
  role: Study Chair
  affiliation: Duke University
  facility: 
  country: United States
  url: http://recovercovid.org/
  description: Related Info
  responsible party type: Sponsor
  mesh term: COVID-19
  mesh term: Post-Acute COVID-19 Syndrome
  sharing ipd: No
  ipd description: The investigators will share the summary of results on the study website: https://recovercovid.org/