<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/NCT03241732</url>
  </required_header>
  <id_info>
    <org_study_id>17D.138</org_study_id>
    <nct_id>NCT03241732</nct_id>
  </id_info>
  <brief_title>PET-MRI in Chronic Traumatic Brain Injury (CTBI)</brief_title>
  <acronym>PET-MRIcTBI</acronym>
  <official_title>Defining Neurobiological Signatures for Chronic Traumatic Brain Injury Using PET-MRI Technology</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Thomas Jefferson University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Thomas Jefferson University</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>
      Chronic Traumatic Brain Injury (cTBI) symptoms exist in individuals who experienced previous&#xD;
      traumatic brain injuries. There are 80-90 thousand individuals who are clinically diagnosed&#xD;
      with cTBI, with estimated costs at greater than 60 billion dollars. However, there is a lack&#xD;
      of studies using comprehensive diagnostic imaging tools to better understand physiological&#xD;
      ramifications of the injury that may help guide therapy. This study uses integrative medicine&#xD;
      approaches for persons with cTBI. Another aim of this study will be a continuation of this&#xD;
      protocol in an effort to address the ongoing distressing physiological and psychological&#xD;
      (anxiety and depression) symptoms associated with cTBI. After completion of the initial 3&#xD;
      study arms, the investigators have amended the protocol to evaluate the physiological and&#xD;
      psychological effects and potential symptom improvement of integrative medicine approaches in&#xD;
      cTBI patients using the Neuro Emotive Technique (NET). Participants may be re-enrolled in the&#xD;
      NET group after completion of participation in the initial study arms. The participants in&#xD;
      the NET substudy will be interviewed about Subjective Units of Distress (SUDS) associated&#xD;
      with the cTBI event initially and after completion of the NET sessions.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this project was to create a comprehensive, extensive, longitudinal diagnostic&#xD;
      evaluation of cTBI patients. The evaluation uses a battery of neurocognitive tests,&#xD;
      laboratory levels of specific inflammatory compounds, and Positron Emission Tomography (PET)&#xD;
      using Fluoro deoxyglucose (FDG) and functional Magnetic Resonance Imaging (fMRI) at baseline&#xD;
      and follow up. Participants were evaluated initially with PET, and then at approximately 3&#xD;
      and 6 months to determine the time course of changes within the brain associated with the&#xD;
      integrative medicine approach. Three groups of participants were enrolled in the study: a&#xD;
      control group, an anti-inflammatory diet group, and an N-acetyl cysteine (NAC) group; NAC is&#xD;
      the N-acetyl derivative of the naturally occurring amino acid, L-cysteine. NAC is a common&#xD;
      over-the-counter supplement that is also available as an injectable pharmaceutical that&#xD;
      protects the liver in cases of acetaminophen overdose. Laboratory studies have displayed some&#xD;
      benefits in use of NAC to reduce markers of oxidative damage, protect against cell death, and&#xD;
      to increase glutathione in blood, which might be useful in preventing oxidative damage in&#xD;
      cTBI patients.&#xD;
&#xD;
      Amendment:&#xD;
&#xD;
      The investigators have amended the original protocol to add a new arm. The purpose of this&#xD;
      sub-study is to 30 enroll subjects who have physiological and/or psychological (depression&#xD;
      and/or anxiety) symptoms associated with cTBI. Enrollment in this arm of the study would&#xD;
      allow for re-enrollment of participants from who still have persistent anxiety, depression&#xD;
      symptoms or distress associated with TBI after completing the first phase of this protocol&#xD;
      (referenced above). Participants would be evaluated (or re-evaluated) with a battery of&#xD;
      neurocognitive tests, including SUDS, NET, and biofeedback measures anxiety levels and&#xD;
      receive baseline PET-MRI imaging and follow up functional MRI, neurocognitive tests,&#xD;
      including SUDS, NET, and biofeedback measures.&#xD;
&#xD;
      In addition to assessing symptoms associated with TBI, subjects will receive five sessions of&#xD;
      Neuro-emotive Technique to address ongoing mood and anxiety symptoms and is conducted by a&#xD;
      trained practitioner with clinical credentials in mental health. Subjects who have&#xD;
      participated in the initial study will be re-consented if enrolled in the Neuro Emotive&#xD;
      Technique Substudy. The investigators will also enroll new subjects with TBI to be enrolled&#xD;
      in the NET substudy cohort. In order to gain a greater understanding of the NET program to&#xD;
      evaluate whether it reduces anxiety and affects the physiology of the brain in persons with&#xD;
      TBI, we believe the potential benefits outweigh the risks. A prescreening interview will be&#xD;
      conducted that inquires about current and past treatment for the TBI. In addition, a brief&#xD;
      Subjective Units of Distress discussion will assist to determine the extent to which the&#xD;
      subject is experiencing distress from TBI or its effects. Upon (re) enrollment and after the&#xD;
      completion of the NET sessions. To assess the level of distress, subjects will receive a&#xD;
      biofeedback testing evaluation that measures heart rate variability (HRV) and galvanic skin&#xD;
      resistance (GSR) in conjunction with recollection of distress.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Enrolling by invitation</overall_status>
  <start_date type="Actual">June 7, 2017</start_date>
  <completion_date type="Anticipated">February 10, 2025</completion_date>
  <primary_completion_date type="Anticipated">February 10, 2025</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>There were two intervention arms of the study and a control group. Enrollment for these groups was 120 subjects. One arm focused on adjusting dietary practices to eat foods that have a lower amount of inflammatory molecules that might help reduce overall inflammation in the brain and body. The second arm was the N-acetyl cysteine group to provide patients with a natural supplement that support antioxidants in the body. The third arm of the study is a waitlist control group.&#xD;
The fourth arm is a substudy that may re-enroll and re-consent 30 subjects from the original 3 groups, and will recruit additional subjects as needed, who continue to have distress associated with TBI. Subjects will receive sessions with the Neuro Emotive Technique. Participants enrolled in the 4th NET group will be counted in the cohort of 30 for the NET substudy.</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>This is an Open Label study.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Fluorodeoxyglucose positron emission tomography (FDG-PET).</measure>
    <time_frame>Baseline in all study arms.</time_frame>
    <description>To measure inflammation and oxidative damage in the brain.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Heart rate variability</measure>
    <time_frame>Screening at Baseline, and if enrolled 90 ± 30 days and if in waitlist 180 ± 30 days</time_frame>
    <description>NET Substudy: This assessment is a Biofeedback evaluation to measure the physiologic level of distress experienced.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Galvanic Skin Temperature</measure>
    <time_frame>Screening at Baseline, and if enrolled 90 ± 30 days and if in waitlist 180 ± 30 days</time_frame>
    <description>NET Substudy: This assessment is a Biofeedback evaluation to measure the physiologic level of distress experienced.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subjective Units of Distress</measure>
    <time_frame>Screening at Baseline, and if enrolled 90 ± 30 days and if in waitlist 180 ± 30 days</time_frame>
    <description>NET Substudy: This assessment is a Likert scale that identifies the level of psychological distress experienced.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional magnetic resonance imaging (fMRI).</measure>
    <time_frame>Baseline, 90 ± 30 days and 180 ± 30 days.</time_frame>
    <description>This scan will be used to assess functional connectivity, tractography, and brain volume.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rivermead Post-Concussion Symptoms Questionnaire.</measure>
    <time_frame>Baseline, 90 ± 30 days and 180 ± 30 days.</time_frame>
    <description>This assessment questionnaire will be used as one of the quality of life measures for the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Beck Depression Inventory (BDI).</measure>
    <time_frame>Baseline, 90 ± 30 days and 180 ± 30 days.</time_frame>
    <description>This assessment questionnaire will be used as one of the psychological evaluation questionnaires for the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Speilberger State Trait Anxiety Inventory (STAI).</measure>
    <time_frame>Baseline, 90 ± 30 days and 180 ± 30 days.</time_frame>
    <description>This assessment questionnaire will be used as one of the psychological evaluation questionnaires for the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Profile of Moods Scale (POMS).</measure>
    <time_frame>Baseline, 90 ± 30 days and 180 ± 30 days.</time_frame>
    <description>This assessment questionnaire will be used as one of the psychological evaluation questionnaires for the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Epworth Sleepiness Scale.</measure>
    <time_frame>Baseline, 90 ± 30 days and 180 ± 30 days.</time_frame>
    <description>This assessment questionnaire will be used as one of the quality of life measures for the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mayo-Portland Adaptability Inventory-4.</measure>
    <time_frame>Baseline, 90 ± 30 days and 180 ± 30 days.</time_frame>
    <description>This assessment questionnaire will be used as one of the quality of life measures for the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Delis Kaplan Executive Function System (DKEFS) color-word interference.</measure>
    <time_frame>Baseline, 90 ± 30 days and 180 ± 30 days.</time_frame>
    <description>This assessment questionnaire may be used as one of the cognitive testings for the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trails A &amp; B.</measure>
    <time_frame>Baseline, 90 ± 30 days and 180 ± 30 days.</time_frame>
    <description>This assessment questionnaire may be used as one of the cognitive testings for the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Forward and reverse digit span.</measure>
    <time_frame>Baseline, 90 ± 30 days and 180 ± 30 days.</time_frame>
    <description>This assessment questionnaire may be used as one of the cognitive testings for the study.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">150</enrollment>
  <condition>Chronic Traumatic Brain Injury</condition>
  <arm_group>
    <arm_group_label>Dietary (AID) Cohort</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Anti-inflammatory Diet: This arm will focus on adjusting dietary practices to eat foods that have lower amounts of inflammatory foods that might help reduce overall inflammation in the brain and body. This arm will introduce patients to an integrative diet that reduces saturated fats and carbohydrates and emphasizes proteins and omega-3 fats that help reduce inflammation and oxidative damage.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intravenous/Oral NAC Cohort</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>N-acetyl Cysteine: This arm provide patients with a natural supplement, n-acetyl cysteine (NAC) which is the N-acetyl derivative of the naturally occurring amino acid, L-cysteine, that supports antioxidants to reduce oxidative damage in the body. NAC is a common over-the-counter supplement. It is used as an injectable pharmaceutical to protect the liver in cases of acetaminophen overdose. Laboratory studies have suggested that NAC might have a beneficial effect in neurodegenerative disorders such as TBI. Patients in this arm will receive IV NAC once a week plus oral NAC supplement 500 mg twice per day for approximately 3 months until the follow up evaluation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Cohort</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Control Group: Standard of Care Treatment for at least 3 months. After the first 3 month, participants in this arm may crossover to the NAC study arm.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Neuro Emotive Technique</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>This arm measures effects of NET in individuals with TBI symptoms by evaluating measures of distress, autonomic reactivity, neuroimaging markers, anxiety, health-related, physiological and psychology-related symptoms. Participants would be evaluated (or re-evaluated) with a battery of neurocognitive tests, and receive baseline PET-MRI and follow up MRI imaging. Subjects will receive a pre-screening evaluation that measures distress by the Subjective Units of Distress interview, biofeedback measures of heart rate variability (HRV) and galvanic skin resistance (GSR) in conjunction with recollection of distress. Subjects will receive five sessions of Neuro-emotive Technique. Subjects who have participated in the initial study will be re-consented if enrolled in the Neuro Emotive Technique Substudy for approximately 2-3 months until the follow up evaluation. SUDS, biofeedback and surveys will be completed again after the NET sessions are complete.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Anti-inflammatory Diet</intervention_name>
    <description>Integrative diet that reduces saturated fats and carbohydrates and emphasizes proteins and omega-3 fats that help reduce inflammation and oxidative damage.</description>
    <arm_group_label>Dietary (AID) Cohort</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>N-acetyl Cysteine</intervention_name>
    <description>Intravenous and Oral n-acetyl cysteine</description>
    <arm_group_label>Intravenous/Oral NAC Cohort</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Neuro Emotive Technique</intervention_name>
    <description>Neuro Emotive Technique sessions</description>
    <arm_group_label>Neuro Emotive Technique</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Individuals with a history of TBI and complaints of persistent symptoms including&#xD;
             cognitive impairment, emotional disturbances, headache, or other symptoms associated&#xD;
             with TBI&#xD;
&#xD;
          -  Anxiety and/or distress associated with TBI or TBI symptoms by measurement with&#xD;
             Subjective Units of Distress, and biofeedback screening&#xD;
&#xD;
          -  Age 18-80 years old&#xD;
&#xD;
          -  Patients had no other pre-existing history (i.e. prior to the TBI) of significant&#xD;
             medical, neurological, or psychological disorders such as schizophrenia or active&#xD;
             substance abuse.&#xD;
&#xD;
          -  Minor, stable health problems that should have no substantial effect on cerebral blood&#xD;
             flow will be allowed (i.e. controlled hypertension, medication controlled diabetes)&#xD;
&#xD;
          -  Able to give informed consent and willing to complete the study&#xD;
&#xD;
          -  Patients will be allowed to be taking medications or supplements at the initial&#xD;
             intake, but they must be on a stable dose regimen for at least 1 month&#xD;
&#xD;
          -  Women of childbearing potential will confirm a negative pregnancy test&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous brain surgery.&#xD;
&#xD;
          -  Cognitive impairment with significant impact on activities of daily living and/or a&#xD;
             score on the Mini-Mental Status examination (or similar) of 25 or lower&#xD;
&#xD;
          -  Intracranial abnormalities that may complicate interpretation of the brain scans&#xD;
             (e.g., stroke, tumor, vascular abnormality affecting the target area).&#xD;
&#xD;
          -  Pregnant or lactating women.&#xD;
&#xD;
          -  Enrollment in active clinical trial/ experimental therapy within the prior 30 days.&#xD;
&#xD;
          -  Any pre-existing medical conditions that may interfere with cerebral function.&#xD;
&#xD;
          -  Subject is unable or unwilling to lie still in the scanner (i.e. due to claustrophobia&#xD;
             or weight &gt; 350 pounds)&#xD;
&#xD;
          -  Subject has metal in their body or other reason that they cannot undergo magnetic&#xD;
             resonance imaging.&#xD;
&#xD;
        Additional exclusionary criteria for the NAC arm:&#xD;
&#xD;
          -  Patients taking medications that might interact with the NAC involved in this study&#xD;
             will be evaluated on a case by case basis by the PI or study physician.&#xD;
&#xD;
          -  Patients that have a history of uncontrolled conditions, e.g.: diabetes, asthma,&#xD;
             gastroesophageal reflex disease, or thyroid conditions&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Andrew B. Newberg, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Thomas Jefferson University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Thomas Jefferson University, Marcus Institute of Integrative Health Centers</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Thomas Jefferson University, Marcus Institute of Integrative Health Centers</name>
      <address>
        <city>Villanova</city>
        <state>Pennsylvania</state>
        <zip>19085</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>July 11, 2017</study_first_submitted>
  <study_first_submitted_qc>August 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2017</study_first_posted>
  <last_update_submitted>March 30, 2023</last_update_submitted>
  <last_update_submitted_qc>March 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 4, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Traumatic Brain Injury</keyword>
  <keyword>TBI</keyword>
  <keyword>Brain Trauma</keyword>
  <keyword>N-acetyl cysteine</keyword>
  <keyword>Concussion</keyword>
  <keyword>NAC</keyword>
  <keyword>Integrative Medicine</keyword>
  <keyword>Functional magnetic resonance imaging or functional MRI</keyword>
  <keyword>fMRI</keyword>
  <keyword>PET</keyword>
  <keyword>Positron emission tomography</keyword>
  <keyword>MRI</keyword>
  <keyword>magnetic resonance imaging</keyword>
  <keyword>Chronic Traumatic Brain Injury</keyword>
  <keyword>Neuro Emotive Technique</keyword>
  <keyword>Subjective Units of Distress (SUDS)</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>Wounds and Injuries</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acetylcysteine</mesh_term>
    <mesh_term>Anti-Inflammatory Agents</mesh_term>
    <mesh_term>N-monoacetylcystine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>January 9, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/32/NCT03241732/ICF_003.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03241732
org study id: 17D.138
nct id: NCT03241732
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Chronic Traumatic Brain Injury (cTBI) symptoms exist in individuals who experienced previous
      traumatic brain injuries. There are 80-90 thousand individuals who are clinically diagnosed
      with cTBI, with estimated costs at greater than 60 billion dollars. However, there is a lack
      of studies using comprehensive diagnostic imaging tools to better understand physiological
      ramifications of the injury that may help guide therapy. This study uses integrative medicine
      approaches for persons with cTBI. Another aim of this study will be a continuation of this
      protocol in an effort to address the ongoing distressing physiological and psychological
      (anxiety and depression) symptoms associated with cTBI. After completion of the initial 3
      study arms, the investigators have amended the protocol to evaluate the physiological and
      psychological effects and potential symptom improvement of integrative medicine approaches in
      cTBI patients using the Neuro Emotive Technique (NET). Participants may be re-enrolled in the
      NET group after completion of participation in the initial study arms. The participants in
      the NET substudy will be interviewed about Subjective Units of Distress (SUDS) associated
      with the cTBI event initially and after completion of the NET sessions.
The purpose of this project was to create a comprehensive, extensive, longitudinal diagnostic
      evaluation of cTBI patients. The evaluation uses a battery of neurocognitive tests,
      laboratory levels of specific inflammatory compounds, and Positron Emission Tomography (PET)
      using Fluoro deoxyglucose (FDG) and functional Magnetic Resonance Imaging (fMRI) at baseline
      and follow up. Participants were evaluated initially with PET, and then at approximately 3
      and 6 months to determine the time course of changes within the brain associated with the
      integrative medicine approach. Three groups of participants were enrolled in the study: a
      control group, an anti-inflammatory diet group, and an N-acetyl cysteine (NAC) group; NAC is
      the N-acetyl derivative of the naturally occurring amino acid, L-cysteine. NAC is a common
      over-the-counter supplement that is also available as an injectable pharmaceutical that
      protects the liver in cases of acetaminophen overdose. Laboratory studies have displayed some
      benefits in use of NAC to reduce markers of oxidative damage, protect against cell death, and
      to increase glutathione in blood, which might be useful in preventing oxidative damage in
      cTBI patients.

      Amendment:

      The investigators have amended the original protocol to add a new arm. The purpose of this
      sub-study is to 30 enroll subjects who have physiological and/or psychological (depression
      and/or anxiety) symptoms associated with cTBI. Enrollment in this arm of the study would
      allow for re-enrollment of participants from who still have persistent anxiety, depression
      symptoms or distress associated with TBI after completing the first phase of this protocol
      (referenced above). Participants would be evaluated (or re-evaluated) with a battery of
      neurocognitive tests, including SUDS, NET, and biofeedback measures anxiety levels and
      receive baseline PET-MRI imaging and follow up functional MRI, neurocognitive tests,
      including SUDS, NET, and biofeedback measures.

      In addition to assessing symptoms associated with TBI, subjects will receive five sessions of
      Neuro-emotive Technique to address ongoing mood and anxiety symptoms and is conducted by a
      trained practitioner with clinical credentials in mental health. Subjects who have
      participated in the initial study will be re-consented if enrolled in the Neuro Emotive
      Technique Substudy. The investigators will also enroll new subjects with TBI to be enrolled
      in the NET substudy cohort. In order to gain a greater understanding of the NET program to
      evaluate whether it reduces anxiety and affects the physiology of the brain in persons with
      TBI, we believe the potential benefits outweigh the risks. A prescreening interview will be
      conducted that inquires about current and past treatment for the TBI. In addition, a brief
      Subjective Units of Distress discussion will assist to determine the extent to which the
      subject is experiencing distress from TBI or its effects. Upon (re) enrollment and after the
      completion of the NET sessions. To assess the level of distress, subjects will receive a
      biofeedback testing evaluation that measures heart rate variability (HRV) and galvanic skin
      resistance (GSR) in conjunction with recollection of distress.
allocation: Non-Randomized
intervention model: Crossover Assignment
intervention model description: There were two intervention arms of the study and a control group. Enrollment for these groups was 120 subjects. One arm focused on adjusting dietary practices to eat foods that have a lower amount of inflammatory molecules that might help reduce overall inflammation in the brain and body. The second arm was the N-acetyl cysteine group to provide patients with a natural supplement that support antioxidants in the body. The third arm of the study is a waitlist control group.
The fourth arm is a substudy that may re-enroll and re-consent 30 subjects from the original 3 groups, and will recruit additional subjects as needed, who continue to have distress associated with TBI. Subjects will receive sessions with the Neuro Emotive Technique. Participants enrolled in the 4th NET group will be counted in the cohort of 30 for the NET substudy.
primary purpose: Diagnostic
masking: None (Open Label)
masking description: This is an Open Label study.
measure: Fluorodeoxyglucose positron emission tomography (FDG-PET).
time frame: Baseline in all study arms.
description: To measure inflammation and oxidative damage in the brain.
measure: Heart rate variability
time frame: Screening at Baseline, and if enrolled 90 ± 30 days and if in waitlist 180 ± 30 days
description: NET Substudy: This assessment is a Biofeedback evaluation to measure the physiologic level of distress experienced.
measure: Galvanic Skin Temperature
time frame: Screening at Baseline, and if enrolled 90 ± 30 days and if in waitlist 180 ± 30 days
description: NET Substudy: This assessment is a Biofeedback evaluation to measure the physiologic level of distress experienced.
measure: Subjective Units of Distress
time frame: Screening at Baseline, and if enrolled 90 ± 30 days and if in waitlist 180 ± 30 days
description: NET Substudy: This assessment is a Likert scale that identifies the level of psychological distress experienced.
measure: Functional magnetic resonance imaging (fMRI).
time frame: Baseline, 90 ± 30 days and 180 ± 30 days.
description: This scan will be used to assess functional connectivity, tractography, and brain volume.
measure: Rivermead Post-Concussion Symptoms Questionnaire.
time frame: Baseline, 90 ± 30 days and 180 ± 30 days.
description: This assessment questionnaire will be used as one of the quality of life measures for the study.
measure: Beck Depression Inventory (BDI).
time frame: Baseline, 90 ± 30 days and 180 ± 30 days.
description: This assessment questionnaire will be used as one of the psychological evaluation questionnaires for the study.
measure: Speilberger State Trait Anxiety Inventory (STAI).
time frame: Baseline, 90 ± 30 days and 180 ± 30 days.
description: This assessment questionnaire will be used as one of the psychological evaluation questionnaires for the study.
measure: Profile of Moods Scale (POMS).
time frame: Baseline, 90 ± 30 days and 180 ± 30 days.
description: This assessment questionnaire will be used as one of the psychological evaluation questionnaires for the study.
measure: Epworth Sleepiness Scale.
time frame: Baseline, 90 ± 30 days and 180 ± 30 days.
description: This assessment questionnaire will be used as one of the quality of life measures for the study.
measure: Mayo-Portland Adaptability Inventory-4.
time frame: Baseline, 90 ± 30 days and 180 ± 30 days.
description: This assessment questionnaire will be used as one of the quality of life measures for the study.
measure: Delis Kaplan Executive Function System (DKEFS) color-word interference.
time frame: Baseline, 90 ± 30 days and 180 ± 30 days.
description: This assessment questionnaire may be used as one of the cognitive testings for the study.
measure: Trails A & B.
time frame: Baseline, 90 ± 30 days and 180 ± 30 days.
description: This assessment questionnaire may be used as one of the cognitive testings for the study.
measure: Forward and reverse digit span.
time frame: Baseline, 90 ± 30 days and 180 ± 30 days.
description: This assessment questionnaire may be used as one of the cognitive testings for the study.
arm group label: Dietary (AID) Cohort
arm group type: Active Comparator
description: Anti-inflammatory Diet: This arm will focus on adjusting dietary practices to eat foods that have lower amounts of inflammatory foods that might help reduce overall inflammation in the brain and body. This arm will introduce patients to an integrative diet that reduces saturated fats and carbohydrates and emphasizes proteins and omega-3 fats that help reduce inflammation and oxidative damage.
arm group label: Intravenous/Oral NAC Cohort
arm group type: Active Comparator
description: N-acetyl Cysteine: This arm provide patients with a natural supplement, n-acetyl cysteine (NAC) which is the N-acetyl derivative of the naturally occurring amino acid, L-cysteine, that supports antioxidants to reduce oxidative damage in the body. NAC is a common over-the-counter supplement. It is used as an injectable pharmaceutical to protect the liver in cases of acetaminophen overdose. Laboratory studies have suggested that NAC might have a beneficial effect in neurodegenerative disorders such as TBI. Patients in this arm will receive IV NAC once a week plus oral NAC supplement 500 mg twice per day for approximately 3 months until the follow up evaluation.
arm group label: Control Cohort
arm group type: No Intervention
description: Control Group: Standard of Care Treatment for at least 3 months. After the first 3 month, participants in this arm may crossover to the NAC study arm.
arm group label: Neuro Emotive Technique
arm group type: Active Comparator
description: This arm measures effects of NET in individuals with TBI symptoms by evaluating measures of distress, autonomic reactivity, neuroimaging markers, anxiety, health-related, physiological and psychology-related symptoms. Participants would be evaluated (or re-evaluated) with a battery of neurocognitive tests, and receive baseline PET-MRI and follow up MRI imaging. Subjects will receive a pre-screening evaluation that measures distress by the Subjective Units of Distress interview, biofeedback measures of heart rate variability (HRV) and galvanic skin resistance (GSR) in conjunction with recollection of distress. Subjects will receive five sessions of Neuro-emotive Technique. Subjects who have participated in the initial study will be re-consented if enrolled in the Neuro Emotive Technique Substudy for approximately 2-3 months until the follow up evaluation. SUDS, biofeedback and surveys will be completed again after the NET sessions are complete.
intervention type: Other
intervention name: Anti-inflammatory Diet
description: Integrative diet that reduces saturated fats and carbohydrates and emphasizes proteins and omega-3 fats that help reduce inflammation and oxidative damage.
arm group label: Dietary (AID) Cohort
intervention type: Dietary Supplement
intervention name: N-acetyl Cysteine
description: Intravenous and Oral n-acetyl cysteine
arm group label: Intravenous/Oral NAC Cohort
intervention type: Behavioral
intervention name: Neuro Emotive Technique
description: Neuro Emotive Technique sessions
arm group label: Neuro Emotive Technique
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Andrew B. Newberg, MD
role: Principal Investigator
affiliation: Thomas Jefferson University
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Brain Injuries
mesh term: Brain Injuries, Traumatic
mesh term: Wounds and Injuries
mesh term: Acetylcysteine
mesh term: Anti-Inflammatory Agents
mesh term: N-monoacetylcystine
sharing ipd: No
provided document: 