<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/NCT03759808</url>
  </required_header>
  <id_info>
    <org_study_id>17-000346</org_study_id>
    <nct_id>NCT03759808</nct_id>
  </id_info>
  <brief_title>Treatment for Patients With Chronic Post-Concussion Symptoms</brief_title>
  <official_title>Cognitive Behavioral Treatment for Patients With Chronic Post-Concussion Symptoms</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, Los Angeles</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of California, Los Angeles</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 current project will examine the effect of a brief psychological intervention on&#xD;
      post-concussion symptoms, neurocognitive function, cerebral blood flow (CBF), and&#xD;
      psychophysiological and salivary cortisol markers of autonomic nervous system (ANS) in a&#xD;
      sample of 20 participants between 13-25 years of age who experience long-term post-concussive&#xD;
      (PC) symptoms 2-9 months post-injury as well as 20 age- and sex-matched controls&#xD;
      (non-injured) participants to provide normative data on all the above measures except for&#xD;
      concussive symptoms.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Participants with concussion will participate in six, home-based interventions designed to&#xD;
      treat cognitive-behavioral factors that are maintaining their symptoms. The investigators&#xD;
      hypothesize that the prolonged PC symptoms are in part due to disruption of autonomic nervous&#xD;
      system function post-injury as well as exacerbation by the psychological response to the&#xD;
      injury. This hypothesis is based on evidence showing that PC symptoms, including headache,&#xD;
      fatigue, dizziness, and heightened anxiety overlap with upregulated sympathetic activity and&#xD;
      elevated levels of salivary cortisol. There is evidence linking cognitive-behavioral factors&#xD;
      (e.g., catastrophizing) to prolonged symptoms of autonomic overactivation after injury (e.g.,&#xD;
      anxiety, pain, etc.). The participants are taught shallow breathing techniques to normalize&#xD;
      parasympathetic activity and provide cognitive-behavioral treatment to reduce psychological&#xD;
      reactions to the injury that exacerbate the autonomic disruption and prolong recovery.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 1, 2018</start_date>
  <completion_date type="Anticipated">February 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">February 1, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>An open trial will be conducted in patients with persistent post-concussion symptoms compared to non-injured controls in order to determine whether the intervention (controlled breathing and cognitive behavioral therapy for anxiety) improves parasympathetic, HPA axis activity and cerebral blood flow, and whether improvement in parasympathetic and HPA axis activity predicts reduction in PPCS symptoms. We will compare baseline evaluations to the evaluation conducted after brief CBT and controlled breathing training to demonstrate the feasibility of normalizing parasympathetic, and HPA axis activity via this intervention. If we obtain the predicted results in the current study we will design a much larger study to identify the mechanisms of change. Healthy, non-injured control participants will provide normative data on all measures except for concussion-relevant outcomes.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Self-Reported Symptoms After Treatment</measure>
    <time_frame>baseline and 6 weeks</time_frame>
    <description>Severity of self-reported symptoms on the Post-Concussion Symptom Inventory</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change Self-Reported Quality of Life After Treatment</measure>
    <time_frame>baseline and 6 weeks</time_frame>
    <description>Self-reported scores on quality of life on Global Quality of Life Scale</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in cerebral blood flow stress after treatment</measure>
    <time_frame>baseline and 6 weeks</time_frame>
    <description>Changes in cerebral blood flow dynamics in bilateral middle cerebral arteries as measured by transcranial doppler.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in peak salivary cortisol after treatment</measure>
    <time_frame>baseline and 6 weeks</time_frame>
    <description>Changes in peak salivary cortisol concentration will be measured in response to stress paradigm. Measurements will be taken just prior to stress paradigm and then 20 minutes after its conclusion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in respiration rate after treatment</measure>
    <time_frame>baseline and 6 weeks</time_frame>
    <description>Changes in respiration rate as measured through capnometer in response to stress paradigm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in end-tidal carbon dioxide after treatment</measure>
    <time_frame>baseline and 6 weeks</time_frame>
    <description>Changes in end-tidal carbon dioxide measurement in response to stress paradigm measured through capnometer in mmHg</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in heart rate after treatment</measure>
    <time_frame>baseline and 6 weeks</time_frame>
    <description>Changes in heart rate (beats per minute) in response to stress paradigm measured through Biopac system.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in blood pressure after treatment</measure>
    <time_frame>baseline and 6 weeks</time_frame>
    <description>Changes in blood pressure (systolic/dyastolic in mmHg) in response to stress paradigm measured through Biopac system.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in depressive symptoms after treatment</measure>
    <time_frame>baseline and 6 weeks</time_frame>
    <description>Self-report measure of cognitive and somatic symptoms of depression, Beck Depression Inventory (BDI-II)</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in anxiety symptoms after treatment</measure>
    <time_frame>baseline and 6 weeks</time_frame>
    <description>Self-report measure of cognitive and somatic symptoms of anxiety, Beck Anxiety Inventory (BAI)</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in sleep quality after treatment</measure>
    <time_frame>baseline and 6 weeks</time_frame>
    <description>Self-report measure of sleep dysfunction, Pittsburgh Sleep Quality Index (PSQI)</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in neurocognitive performance after treatment</measure>
    <time_frame>baseline and 6 weeks</time_frame>
    <description>Selected subtest performance on attention, learning and memory, processing speed, and verbal fluency as measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) standardized assessment.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in perceived cognitive exertion after treatment</measure>
    <time_frame>baseline and 6 weeks</time_frame>
    <description>Change in self-reported physical, emotional, and perceived cognitive symptoms from pre- to post-neurocognitive assessment.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in illness perception after treatment</measure>
    <time_frame>baseline and 6 weeks</time_frame>
    <description>Change in self-reported perception of illness as measured by the Brief Illness Perception Questionnaire.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in behavioral avoidance and distress after treatment</measure>
    <time_frame>baseline and 6 weeks</time_frame>
    <description>Change in self-reported behavioral avoidance and distress due to anxiety as measured by the UCLA Behavioral Avoidance and Distress Scale</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in disability perception due to injury after treatment</measure>
    <time_frame>baseline and 6 weeks</time_frame>
    <description>Change in self-reported disability in social, occupational, and family/home functioning as measured by the Sheehan Disability Scale</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in orthostatic blood pressure after treatment</measure>
    <time_frame>baseline and 6 weeks</time_frame>
    <description>Change in orthostatic blood pressure obtained via measurements in three different positions: supine, upright sitting, and standing, each held for 5 minutes. Measurement obtained via Biopac double finger cuff.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Mild Traumatic Brain Injury</condition>
  <condition>Concussion Post Syndrome</condition>
  <arm_group>
    <arm_group_label>Persistent Post-Concussion Symptoms</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Concussed participants with persistent post-concussion symptoms (PPCS) who receive the psychological intervention.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Psychological Intervention</intervention_name>
    <description>Psychological treatment protocol designed to treat anxiety and avoidance in an adolescent/young adult population. The focus of treatment will be to address cognitive and behavioral factors associated with prolonged symptoms. Cognitive factors that may be addressed include, but are not limited to, catastrophizing, black or white thinking, and false expectations. Behavior factors that may be addressed include, but are not limited to, avoidance, relaxation, and behavioral activation. The psychological intervention is also designed to help reduce psychophysiological arousal associated with anxiety and stress. Participants will also be taught controlled shallow breathing exercises designed to normalize the ratio of sympathetic/parasympathetic activity.</description>
    <arm_group_label>Persistent Post-Concussion Symptoms</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria for patients:&#xD;
&#xD;
          -  Between the ages of 13-25&#xD;
&#xD;
          -  Diagnosed with a concussion or mild traumatic brain injury by a physician&#xD;
&#xD;
          -  Currently experiencing post-concussive symptoms for at least two months after their&#xD;
             injury but no longer than 9 months.&#xD;
&#xD;
          -  Fluent English speaker&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of/or comorbid neurological conditions that might affect performance&#xD;
             (including history of stroke, seizure disorder, moderate to severe traumatic brain&#xD;
             injury, anoxia)&#xD;
&#xD;
          -  Severe cardiovascular conditions.&#xD;
&#xD;
          -  History of psychosis and current substance abuse or dependence.&#xD;
&#xD;
          -  Current severe symptoms of depression and/or anxiety.&#xD;
&#xD;
        Additional Exclusion Criteria for Controls:&#xD;
&#xD;
        * No history of concussion in the past year.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>13 Years</minimum_age>
    <maximum_age>25 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Robert Asarnow, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, Los Angeles</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Aliyah R Snyder, PhD</last_name>
    <phone>3109169460</phone>
    <email>asnyder@mednet.ucla.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of California, Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Aliyah R Snyder, PhD</last_name>
      <phone>310-916-9460</phone>
      <email>hips@mednet.ucla.ed</email>
    </contact>
    <contact_backup>
      <last_name>Alexandra Tanner, MS</last_name>
      <email>tannera@ucla.edu</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>September 20, 2018</study_first_submitted>
  <study_first_submitted_qc>November 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 30, 2018</study_first_posted>
  <last_update_submitted>October 28, 2021</last_update_submitted>
  <last_update_submitted_qc>October 28, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 29, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of California, Los Angeles</investigator_affiliation>
    <investigator_full_name>Robert F. Asarnow, Ph.D</investigator_full_name>
    <investigator_title>Study Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>post-concussion syndrome</keyword>
  <keyword>mild traumatic brain injury</keyword>
  <keyword>autonomic dysfunction</keyword>
  <keyword>concussion</keyword>
  <keyword>capnometry-assisted respiratory training</keyword>
  <keyword>cognitive behavioral therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Injuries</mesh_term>
    <mesh_term>Brain Injuries, Traumatic</mesh_term>
    <mesh_term>Brain Concussion</mesh_term>
    <mesh_term>Post-Concussion Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>All individual participant data that underlie results in a publication will be shared if requested by other researchers. These data will include Study Protocol, Statistical Analysis Plan, and Clinical Study Report. Data will be made available for sharing 6 months after publication and be available for a time frame of 2 years following initial publication. Access to IPD will be considered for researchers with a graduate degree or above for post-hoc analyses or replication efforts. Applications to access individual participant data will be reviewed by principal investigator and appointed co-investigators.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>6 months following initial publication, lasting for 2 years after initial publication.</ipd_time_frame>
    <ipd_access_criteria>Access to individual participant data will be considered for researchers with a graduate degree or above for post-hoc analyses or replication efforts. Applications to access individual participant data will be reviewed by principal investigator and appointed co-investigators.</ipd_access_criteria>
  </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/NCT03759808
org study id: 17-000346
nct id: NCT03759808
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The current project will examine the effect of a brief psychological intervention on
      post-concussion symptoms, neurocognitive function, cerebral blood flow (CBF), and
      psychophysiological and salivary cortisol markers of autonomic nervous system (ANS) in a
      sample of 20 participants between 13-25 years of age who experience long-term post-concussive
      (PC) symptoms 2-9 months post-injury as well as 20 age- and sex-matched controls
      (non-injured) participants to provide normative data on all the above measures except for
      concussive symptoms.
Participants with concussion will participate in six, home-based interventions designed to
      treat cognitive-behavioral factors that are maintaining their symptoms. The investigators
      hypothesize that the prolonged PC symptoms are in part due to disruption of autonomic nervous
      system function post-injury as well as exacerbation by the psychological response to the
      injury. This hypothesis is based on evidence showing that PC symptoms, including headache,
      fatigue, dizziness, and heightened anxiety overlap with upregulated sympathetic activity and
      elevated levels of salivary cortisol. There is evidence linking cognitive-behavioral factors
      (e.g., catastrophizing) to prolonged symptoms of autonomic overactivation after injury (e.g.,
      anxiety, pain, etc.). The participants are taught shallow breathing techniques to normalize
      parasympathetic activity and provide cognitive-behavioral treatment to reduce psychological
      reactions to the injury that exacerbate the autonomic disruption and prolong recovery.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: An open trial will be conducted in patients with persistent post-concussion symptoms compared to non-injured controls in order to determine whether the intervention (controlled breathing and cognitive behavioral therapy for anxiety) improves parasympathetic, HPA axis activity and cerebral blood flow, and whether improvement in parasympathetic and HPA axis activity predicts reduction in PPCS symptoms. We will compare baseline evaluations to the evaluation conducted after brief CBT and controlled breathing training to demonstrate the feasibility of normalizing parasympathetic, and HPA axis activity via this intervention. If we obtain the predicted results in the current study we will design a much larger study to identify the mechanisms of change. Healthy, non-injured control participants will provide normative data on all measures except for concussion-relevant outcomes.
primary purpose: Treatment
masking: None (Open Label)
measure: Change in Self-Reported Symptoms After Treatment
time frame: baseline and 6 weeks
description: Severity of self-reported symptoms on the Post-Concussion Symptom Inventory
measure: Change Self-Reported Quality of Life After Treatment
time frame: baseline and 6 weeks
description: Self-reported scores on quality of life on Global Quality of Life Scale
measure: Change in cerebral blood flow stress after treatment
time frame: baseline and 6 weeks
description: Changes in cerebral blood flow dynamics in bilateral middle cerebral arteries as measured by transcranial doppler.
measure: Change in peak salivary cortisol after treatment
time frame: baseline and 6 weeks
description: Changes in peak salivary cortisol concentration will be measured in response to stress paradigm. Measurements will be taken just prior to stress paradigm and then 20 minutes after its conclusion.
measure: Change in respiration rate after treatment
time frame: baseline and 6 weeks
description: Changes in respiration rate as measured through capnometer in response to stress paradigm
measure: Change in end-tidal carbon dioxide after treatment
time frame: baseline and 6 weeks
description: Changes in end-tidal carbon dioxide measurement in response to stress paradigm measured through capnometer in mmHg
measure: Change in heart rate after treatment
time frame: baseline and 6 weeks
description: Changes in heart rate (beats per minute) in response to stress paradigm measured through Biopac system.
measure: Change in blood pressure after treatment
time frame: baseline and 6 weeks
description: Changes in blood pressure (systolic/dyastolic in mmHg) in response to stress paradigm measured through Biopac system.
measure: Change in depressive symptoms after treatment
time frame: baseline and 6 weeks
description: Self-report measure of cognitive and somatic symptoms of depression, Beck Depression Inventory (BDI-II)
measure: Change in anxiety symptoms after treatment
time frame: baseline and 6 weeks
description: Self-report measure of cognitive and somatic symptoms of anxiety, Beck Anxiety Inventory (BAI)
measure: Change in sleep quality after treatment
time frame: baseline and 6 weeks
description: Self-report measure of sleep dysfunction, Pittsburgh Sleep Quality Index (PSQI)
measure: Change in neurocognitive performance after treatment
time frame: baseline and 6 weeks
description: Selected subtest performance on attention, learning and memory, processing speed, and verbal fluency as measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) standardized assessment.
measure: Change in perceived cognitive exertion after treatment
time frame: baseline and 6 weeks
description: Change in self-reported physical, emotional, and perceived cognitive symptoms from pre- to post-neurocognitive assessment.
measure: Change in illness perception after treatment
time frame: baseline and 6 weeks
description: Change in self-reported perception of illness as measured by the Brief Illness Perception Questionnaire.
measure: Change in behavioral avoidance and distress after treatment
time frame: baseline and 6 weeks
description: Change in self-reported behavioral avoidance and distress due to anxiety as measured by the UCLA Behavioral Avoidance and Distress Scale
measure: Change in disability perception due to injury after treatment
time frame: baseline and 6 weeks
description: Change in self-reported disability in social, occupational, and family/home functioning as measured by the Sheehan Disability Scale
measure: Change in orthostatic blood pressure after treatment
time frame: baseline and 6 weeks
description: Change in orthostatic blood pressure obtained via measurements in three different positions: supine, upright sitting, and standing, each held for 5 minutes. Measurement obtained via Biopac double finger cuff.
arm group label: Persistent Post-Concussion Symptoms
arm group type: Experimental
description: Concussed participants with persistent post-concussion symptoms (PPCS) who receive the psychological intervention.
intervention type: Behavioral
intervention name: Psychological Intervention
description: Psychological treatment protocol designed to treat anxiety and avoidance in an adolescent/young adult population. The focus of treatment will be to address cognitive and behavioral factors associated with prolonged symptoms. Cognitive factors that may be addressed include, but are not limited to, catastrophizing, black or white thinking, and false expectations. Behavior factors that may be addressed include, but are not limited to, avoidance, relaxation, and behavioral activation. The psychological intervention is also designed to help reduce psychophysiological arousal associated with anxiety and stress. Participants will also be taught controlled shallow breathing exercises designed to normalize the ratio of sympathetic/parasympathetic activity.
arm group label: Persistent Post-Concussion Symptoms
criteria: 
gender: All
minimum age: 13 Years
maximum age: 25 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Robert Asarnow, PhD
role: Principal Investigator
affiliation: University of California, Los Angeles
last name: Aliyah R Snyder, PhD
phone: 3109169460
email: asnyder@mednet.ucla.edu
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of California, Los Angeles
investigator full name: Robert F. Asarnow, Ph.D
investigator title: Study Principal Investigator
mesh term: Brain Injuries
mesh term: Brain Injuries, Traumatic
mesh term: Brain Concussion
mesh term: Post-Concussion Syndrome
sharing ipd: Yes
ipd description: All individual participant data that underlie results in a publication will be shared if requested by other researchers. These data will include Study Protocol, Statistical Analysis Plan, and Clinical Study Report. Data will be made available for sharing 6 months after publication and be available for a time frame of 2 years following initial publication. Access to IPD will be considered for researchers with a graduate degree or above for post-hoc analyses or replication efforts. Applications to access individual participant data will be reviewed by principal investigator and appointed co-investigators.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: 6 months following initial publication, lasting for 2 years after initial publication.
ipd access criteria: Access to individual participant data will be considered for researchers with a graduate degree or above for post-hoc analyses or replication efforts. Applications to access individual participant data will be reviewed by principal investigator and appointed co-investigators.