<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/NCT04453631</url>
  </required_header>
  <id_info>
    <org_study_id>tDCS-UP</org_study_id>
    <nct_id>NCT04453631</nct_id>
  </id_info>
  <brief_title>tDCS and Psychotherapy for the Treatment of Anxiety Disorders</brief_title>
  <acronym>tDCSplusUP</acronym>
  <official_title>The Efficacy of Transcranial Direct Current Stimulation Combined With the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders: a Double Blind, Sham Controlled, Randomized Factorial Designed Study for Anxiety Disorders</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Coimbra</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Coimbra</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main goal of the study is to test the efficacy of tDCS in combination with the Unified&#xD;
      Protocol for transdiagnostic treatment of emotional disorders, to reduce anxiety symptoms in&#xD;
      a mixed anxiety disorders sample, as assessed by the Hamilton Anxiety Rating Scale (HARS;&#xD;
      Hamilton, 1959).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Participants will be randomly allocated to one of four parallel experimental arms, within a&#xD;
      2X2 factorial design in which two interventions (tDCS and CBT-UP) will be delivered, and&#xD;
      assessed according to two levels (e.g., intervention vs. no intervention).&#xD;
&#xD;
      Each study participant will assigned to one factor level. Four intervention groups are&#xD;
      defined&#xD;
&#xD;
        1. active tDCS + CBT-UP&#xD;
&#xD;
        2. sham tDCS + CBT-UP&#xD;
&#xD;
        3. active tDCS + Psychoeducation&#xD;
&#xD;
        4. sham tDCS + Psychoeducation&#xD;
&#xD;
      The four arms allow to experimentally control the two active therapeutic interventions:&#xD;
      active tDCS and CBT-UP. Sham tDCS is the control for active tDCS and psychoeducation is the&#xD;
      control condition for CBT-UP.&#xD;
&#xD;
      The intervention will last for 15 weeks, and all groups will comply with the same&#xD;
      intervention structure according to the examination plan established in the protocol:&#xD;
&#xD;
        -  week 1-2: 1 CBT-UP session/week&#xD;
&#xD;
        -  week 3-4: 5 tDCS sessions and 1 CBT-UP session/week&#xD;
&#xD;
        -  week 5-8: 2 tDCS sessions and 1 CBT-UP session/week&#xD;
&#xD;
        -  week 9-14: 1 tDCS session and 1 CBT-UP session/week&#xD;
&#xD;
        -  week 15: 1 CBT-UP session&#xD;
&#xD;
      The treatment will consist of 26 transcranial direct current stimulation sessions, each&#xD;
      lasting 20 minutes, with a current intensity of 2 mA, the cathode placed over the right&#xD;
      dorsolateral prefrontal cortex and the anode placed over the left deltoid muscle. tDCS will&#xD;
      be combined with cognitive-behavioral therapy, in particular following the unified protocol&#xD;
      for transdiagnostic treatment of emotional disorders (Barlow et al. 2018).&#xD;
&#xD;
      Safety:&#xD;
&#xD;
      No serious adverse effects are expected with conventional tDCS protocols in humans (≤40 min,&#xD;
      ≤4 mA; conclusions from a meta-analysis observing &gt;33200 sessions, &gt;1000 subjects with&#xD;
      repeated sessions; Bikson et al., 2016).&#xD;
&#xD;
      Plans for treatment or care after the subject has ended his/her participation in the trial:&#xD;
&#xD;
      Patients will be recommended and offered the best treatment as evidenced by the trial&#xD;
      results. For patients that already completed that intervention further standard&#xD;
      psychological/psychiatric treatment will be recommended according to patients' status.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">January 3, 2023</start_date>
  <completion_date type="Anticipated">July 2024</completion_date>
  <primary_completion_date type="Anticipated">January 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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Hamilton Anxiety Rating Scale (HARS; Hamilton, 1959)</measure>
    <time_frame>At week 8th, 15th (middle and end of treatment) and 6 months follow-up</time_frame>
    <description>The mean change in the Hamilton Anxiety Rating Scale (HARS; Hamilton, 1959) score, from baseline. HARS total score ranges from 0 to 56, where higher values indicate higher anxiety symptom's severity.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Response to treatment</measure>
    <time_frame>At week 8th, 15th (middle and end of treatment) and 6 months follow-up.</time_frame>
    <description>Defined as reduction of total Hamilton Anxiety Rating Scale (HARS; Hamilton, 1959) score by ≥ 50%.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Remission to treatment</measure>
    <time_frame>At week 8th, 15th (middle and end of treatment) and 6 months follow-up.</time_frame>
    <description>Defined as reduction of total Hamilton Anxiety Rating Scale (HARS; Hamilton, 1959) to scores lower than 18 (indicating mild anxiety severity).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hamilton Depression Rating Scale (HRSD; Hamilton, 1960)</measure>
    <time_frame>At week 8th, 15th (middle and end of treatment) and 6 months follow-up.</time_frame>
    <description>The mean change in the Hamilton Depression Rating Scale (HRSD; Hamilton, 1960) score, from baseline. HDRS total score ranges from 0 to 75, where higher values indicate higher depressive symptoms' severity.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Anxiety Disorders</condition>
  <arm_group>
    <arm_group_label>active tDCS + CBT-UP</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Active tDCS combined with the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>sham tDCS + CBT-UP</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Sham tDCS (control for active tDCS) combined with the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>active tDCS + Psychoeducation</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Active tDCS combined with psychoeducation (control condition for CBT-UP).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>sham tDCS + Psychoeducation</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Sham tDCS combined with psychoeducation (control conditions for active tDCS and CBT-UP).</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>active tDCS</intervention_name>
    <description>26 transcranial direct current stimulation sessions, each lasting 20 minutes, with a current intensity of 2 mA, the cathode placed over the right dorsolateral prefrontal cortex and the anode placed over the left deltoid muscle.</description>
    <arm_group_label>active tDCS + CBT-UP</arm_group_label>
    <arm_group_label>active tDCS + Psychoeducation</arm_group_label>
    <other_name>Transcranial Direct Current Stimulation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>sham tDCS</intervention_name>
    <description>tDCS is controlled in this intervention: sham mode.</description>
    <arm_group_label>sham tDCS + CBT-UP</arm_group_label>
    <arm_group_label>sham tDCS + Psychoeducation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>CBT-UP</intervention_name>
    <description>15 psychotherapy sessions (1/week) following the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders developed by Barlow et al. 2018.</description>
    <arm_group_label>active tDCS + CBT-UP</arm_group_label>
    <arm_group_label>sham tDCS + CBT-UP</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Psychoeducation</intervention_name>
    <description>To control for the cognitive-behavioral intervention we will use psychoeducation materials.</description>
    <arm_group_label>active tDCS + Psychoeducation</arm_group_label>
    <arm_group_label>sham tDCS + Psychoeducation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of generalized anxiety disorder, specific phobia, panic disorder,&#xD;
             agoraphobia, or social anxiety disorder.&#xD;
&#xD;
          -  Willing to participate and to give written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Contra-indications to tDCS use:&#xD;
&#xD;
               -  Presence of a cardiac or neurological condition&#xD;
&#xD;
               -  Metallic implants&#xD;
&#xD;
               -  If contact with scalp is not possible&#xD;
&#xD;
               -  Have had a head injury resulting in a loss of consciousness that has required&#xD;
                  further investigation&#xD;
&#xD;
               -  History of seizures&#xD;
&#xD;
               -  Epilepsy or a history of epilepsy&#xD;
&#xD;
               -  Past adverse effects with non-invasive stimulation treatments&#xD;
&#xD;
          2. Current diagnosis of another psychiatric disorder (except for depression, as long as&#xD;
             secondary diagnosis), psychoactive medication or psychological treatment&#xD;
&#xD;
          3. Left-handedness&#xD;
&#xD;
          4. Pregnancy&#xD;
&#xD;
          5. Skin condition on the stimulation target area&#xD;
&#xD;
          6. Recreational drug use&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <reference>
    <citation>HAMILTON M. The assessment of anxiety states by rating. Br J Med Psychol. 1959;32(1):50-5. doi: 10.1111/j.2044-8341.1959.tb00467.x. No abstract available.</citation>
    <PMID>13638508</PMID>
  </reference>
  <reference>
    <citation>HAMILTON M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960 Feb;23(1):56-62. doi: 10.1136/jnnp.23.1.56. No abstract available.</citation>
    <PMID>14399272</PMID>
  </reference>
  <reference>
    <citation>Bikson M, Grossman P, Thomas C, Zannou AL, Jiang J, Adnan T, Mourdoukoutas AP, Kronberg G, Truong D, Boggio P, Brunoni AR, Charvet L, Fregni F, Fritsch B, Gillick B, Hamilton RH, Hampstead BM, Jankord R, Kirton A, Knotkova H, Liebetanz D, Liu A, Loo C, Nitsche MA, Reis J, Richardson JD, Rotenberg A, Turkeltaub PE, Woods AJ. Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. Brain Stimul. 2016 Sep-Oct;9(5):641-661. doi: 10.1016/j.brs.2016.06.004. Epub 2016 Jun 15.</citation>
    <PMID>27372845</PMID>
  </reference>
  <reference>
    <citation>Barlow DH, Farchione TJ, Bullis JR, Gallagher MW, Murray-Latin H, Sauer-Zavala S, Bentley KH, Thompson-Hollands J, Conklin LR, Boswell JF, Ametaj A, Carl JR, Boettcher HT, Cassiello-Robbins C. The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders Compared With Diagnosis-Specific Protocols for Anxiety Disorders: A Randomized Clinical Trial. JAMA Psychiatry. 2017 Sep 1;74(9):875-884. doi: 10.1001/jamapsychiatry.2017.2164.</citation>
    <PMID>28768327</PMID>
  </reference>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>June 26, 2020</study_first_submitted>
  <study_first_submitted_qc>June 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 1, 2020</study_first_posted>
  <last_update_submitted>May 19, 2022</last_update_submitted>
  <last_update_submitted_qc>May 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 20, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Coimbra</investigator_affiliation>
    <investigator_full_name>Ana Ganho Ávila</investigator_full_name>
    <investigator_title>Integrated Researcher</investigator_title>
  </responsible_party>
  <keyword>anxiety disorders</keyword>
  <keyword>tDCS</keyword>
  <keyword>Unified Protocol</keyword>
  <keyword>RCT</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anxiety Disorders</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</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/NCT04453631
org study id: tDCS-UP
nct id: NCT04453631
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The main goal of the study is to test the efficacy of tDCS in combination with the Unified
      Protocol for transdiagnostic treatment of emotional disorders, to reduce anxiety symptoms in
      a mixed anxiety disorders sample, as assessed by the Hamilton Anxiety Rating Scale (HARS;
      Hamilton, 1959).
Participants will be randomly allocated to one of four parallel experimental arms, within a
      2X2 factorial design in which two interventions (tDCS and CBT-UP) will be delivered, and
      assessed according to two levels (e.g., intervention vs. no intervention).

      Each study participant will assigned to one factor level. Four intervention groups are
      defined

        1. active tDCS + CBT-UP

        2. sham tDCS + CBT-UP

        3. active tDCS + Psychoeducation

        4. sham tDCS + Psychoeducation

      The four arms allow to experimentally control the two active therapeutic interventions:
      active tDCS and CBT-UP. Sham tDCS is the control for active tDCS and psychoeducation is the
      control condition for CBT-UP.

      The intervention will last for 15 weeks, and all groups will comply with the same
      intervention structure according to the examination plan established in the protocol:

        -  week 1-2: 1 CBT-UP session/week

        -  week 3-4: 5 tDCS sessions and 1 CBT-UP session/week

        -  week 5-8: 2 tDCS sessions and 1 CBT-UP session/week

        -  week 9-14: 1 tDCS session and 1 CBT-UP session/week

        -  week 15: 1 CBT-UP session

      The treatment will consist of 26 transcranial direct current stimulation sessions, each
      lasting 20 minutes, with a current intensity of 2 mA, the cathode placed over the right
      dorsolateral prefrontal cortex and the anode placed over the left deltoid muscle. tDCS will
      be combined with cognitive-behavioral therapy, in particular following the unified protocol
      for transdiagnostic treatment of emotional disorders (Barlow et al. 2018).

      Safety:

      No serious adverse effects are expected with conventional tDCS protocols in humans (≤40 min,
      ≤4 mA; conclusions from a meta-analysis observing >33200 sessions, >1000 subjects with
      repeated sessions; Bikson et al., 2016).

      Plans for treatment or care after the subject has ended his/her participation in the trial:

      Patients will be recommended and offered the best treatment as evidenced by the trial
      results. For patients that already completed that intervention further standard
      psychological/psychiatric treatment will be recommended according to patients' status.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Hamilton Anxiety Rating Scale (HARS; Hamilton, 1959)
time frame: At week 8th, 15th (middle and end of treatment) and 6 months follow-up
description: The mean change in the Hamilton Anxiety Rating Scale (HARS; Hamilton, 1959) score, from baseline. HARS total score ranges from 0 to 56, where higher values indicate higher anxiety symptom's severity.
measure: Response to treatment
time frame: At week 8th, 15th (middle and end of treatment) and 6 months follow-up.
description: Defined as reduction of total Hamilton Anxiety Rating Scale (HARS; Hamilton, 1959) score by ≥ 50%.
measure: Remission to treatment
time frame: At week 8th, 15th (middle and end of treatment) and 6 months follow-up.
description: Defined as reduction of total Hamilton Anxiety Rating Scale (HARS; Hamilton, 1959) to scores lower than 18 (indicating mild anxiety severity).
measure: Hamilton Depression Rating Scale (HRSD; Hamilton, 1960)
time frame: At week 8th, 15th (middle and end of treatment) and 6 months follow-up.
description: The mean change in the Hamilton Depression Rating Scale (HRSD; Hamilton, 1960) score, from baseline. HDRS total score ranges from 0 to 75, where higher values indicate higher depressive symptoms' severity.
arm group label: active tDCS + CBT-UP
arm group type: Experimental
description: Active tDCS combined with the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders.
arm group label: sham tDCS + CBT-UP
arm group type: Active Comparator
description: Sham tDCS (control for active tDCS) combined with the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders.
arm group label: active tDCS + Psychoeducation
arm group type: Active Comparator
description: Active tDCS combined with psychoeducation (control condition for CBT-UP).
arm group label: sham tDCS + Psychoeducation
arm group type: Placebo Comparator
description: Sham tDCS combined with psychoeducation (control conditions for active tDCS and CBT-UP).
intervention type: Device
intervention name: active tDCS
description: 26 transcranial direct current stimulation sessions, each lasting 20 minutes, with a current intensity of 2 mA, the cathode placed over the right dorsolateral prefrontal cortex and the anode placed over the left deltoid muscle.
arm group label: active tDCS + CBT-UP
arm group label: active tDCS + Psychoeducation
other name: Transcranial Direct Current Stimulation
intervention type: Device
intervention name: sham tDCS
description: tDCS is controlled in this intervention: sham mode.
arm group label: sham tDCS + CBT-UP
arm group label: sham tDCS + Psychoeducation
intervention type: Behavioral
intervention name: CBT-UP
description: 15 psychotherapy sessions (1/week) following the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders developed by Barlow et al. 2018.
arm group label: active tDCS + CBT-UP
arm group label: sham tDCS + CBT-UP
intervention type: Behavioral
intervention name: Psychoeducation
description: To control for the cognitive-behavioral intervention we will use psychoeducation materials.
arm group label: active tDCS + Psychoeducation
arm group label: sham tDCS + Psychoeducation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
citation: HAMILTON M. The assessment of anxiety states by rating. Br J Med Psychol. 1959;32(1):50-5. doi: 10.1111/j.2044-8341.1959.tb00467.x. No abstract available.
PMID: 13638508
citation: HAMILTON M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960 Feb;23(1):56-62. doi: 10.1136/jnnp.23.1.56. No abstract available.
PMID: 14399272
citation: Bikson M, Grossman P, Thomas C, Zannou AL, Jiang J, Adnan T, Mourdoukoutas AP, Kronberg G, Truong D, Boggio P, Brunoni AR, Charvet L, Fregni F, Fritsch B, Gillick B, Hamilton RH, Hampstead BM, Jankord R, Kirton A, Knotkova H, Liebetanz D, Liu A, Loo C, Nitsche MA, Reis J, Richardson JD, Rotenberg A, Turkeltaub PE, Woods AJ. Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. Brain Stimul. 2016 Sep-Oct;9(5):641-661. doi: 10.1016/j.brs.2016.06.004. Epub 2016 Jun 15.
PMID: 27372845
citation: Barlow DH, Farchione TJ, Bullis JR, Gallagher MW, Murray-Latin H, Sauer-Zavala S, Bentley KH, Thompson-Hollands J, Conklin LR, Boswell JF, Ametaj A, Carl JR, Boettcher HT, Cassiello-Robbins C. The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders Compared With Diagnosis-Specific Protocols for Anxiety Disorders: A Randomized Clinical Trial. JAMA Psychiatry. 2017 Sep 1;74(9):875-884. doi: 10.1001/jamapsychiatry.2017.2164.
PMID: 28768327
responsible party type: Principal Investigator
investigator affiliation: University of Coimbra
investigator full name: Ana Ganho Ávila
investigator title: Integrated Researcher
mesh term: Anxiety Disorders
sharing ipd: Yes