<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/NCT02251743</url>
  </required_header>
  <id_info>
    <org_study_id>2013H0417</org_study_id>
    <secondary_id>1R01MH100144-01A1</secondary_id>
    <nct_id>NCT02251743</nct_id>
  </id_info>
  <brief_title>Double-Blind 2-Site Randomized Clinical Trial of Neurofeedback for ADHD</brief_title>
  <official_title>Double-Blind 2-Site Randomized Clinical Trial of Neurofeedback for ADHD</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ohio State University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Mental Health (NIMH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of North Carolina</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Ohio State University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Additional treatments with long-term benefit for attention-deficit/hyperactivity disorder&#xD;
      (ADHD) are needed; one of the more promising is neurofeedback (EEG biofeedback), which has&#xD;
      several randomized controlled trials showing significant benefit, but which are inconclusive&#xD;
      because they were not double-blinded; the benefit could have been nonspecific (placebo&#xD;
      response). Because of neurofeedback's labor-intensive cost (1 treatment costing as much as a&#xD;
      month's medication), It is important to know how much specific benefit it yields. This 2-&#xD;
      site placebo-controlled double-blind randomized clinical trial is the first to test for a&#xD;
      specific benefit of neurofeedback with adequate power, the first designed and implemented&#xD;
      collaboratively by experts in neurofeedback, ADHD, and clinical trials, the first to&#xD;
      rigorously monitor quality not only of treatment, but also of placebo and blinding, and the&#xD;
      first to follow up for 2 years to examine enduring effect; the results, whether positive or&#xD;
      negative, will provide evidence for clinical practice and public policy regarding ADHD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Current established, evidence-based treatments for attention-deficit/hyperactivity disorder&#xD;
      (ADHD) are incompletely effective and not universally acceptable, and appear to wane in&#xD;
      effect over time despite significant immediate benefit. E.g., FDA-approved medication, which&#xD;
      shows large acute benefit, leaves a third of children only partially treated even when&#xD;
      combined with behavioral treatment, and has not been demonstrated effective beyond 2 years.&#xD;
      Additional treatments are needed that are effective with persisting benefit, preferably&#xD;
      related to a biomarker predicting treatment response. A good candidate is&#xD;
      electroencephalographic (EEG) biofeedback, called neurofeedback (NF). It is based on 1)&#xD;
      observations that patients with ADHD often have excessive theta band (4-8 Hz) quantitative&#xD;
      EEG power, low beta band (13-21 Hz) power, and excessive theta beta ratio (TBR), and 2)&#xD;
      theoretical application of operant conditioning to correct this EEG imbalance. Metaanalysis&#xD;
      of 6 randomized clinical trials found a large benefit for inattentive symptoms and medium&#xD;
      benefit for hyperactive-impulsive symptoms. Unfortunately, none of these were blinded. Three&#xD;
      of 4 small blinded studies found no advantage for NF over sham, but used suboptimal NF,&#xD;
      leaving the situation inconclusive. Because of the expense and time required by NF, there is&#xD;
      a public health need to determine whether it has a specific effect beyond the obvious&#xD;
      nonspecific benefit of doing a focused activity several times a week with a&#xD;
      friendly,encouraging adult who reinforces for attending to the task. Experts in NF, ADHD,&#xD;
      clinical trials, statistics, and data management have joined to design a double-blind&#xD;
      sham-controlled randomized clinical trial to answer several pressing scientific and clinical&#xD;
      questions in a way that will be credible to all. At each of 2 sites (1 university &amp; 1 NF&#xD;
      clinic) 70 children (total N=140) age 7 through 10 with rigorously diagnosed moderate to&#xD;
      severe ADHD and TBR&gt;5 will be randomized in a 3:2 ratio to active TBR downtraining by NF vs.&#xD;
      a sham training of equal duration, intensity, and appearance. To keep both participants and&#xD;
      study staff blind, the sham will utilize pre-recorded EEGs with the participant's artifacts&#xD;
      superimposed. The sham will be programmed into the equipment via internet by an off-site&#xD;
      statistician-guided person who has no contact with participants. Treatment fidelity will be&#xD;
      trained and monitored by 2 acknowledged NF leaders in a manner that protects blinding.&#xD;
      Multi-domain assessments at baseline, mid-treatment, treatment end, and follow-ups at 6&#xD;
      months, 1 year, and 2 years will include parent and teacher ratings of symptoms &amp; impairment,&#xD;
      neuropsychological tests,clinician ratings, and quantitative EEG as well as tests of blinding&#xD;
      and of sham inertness. Hypotheses include that NF will improve parent- and teacher-rated&#xD;
      inattentive symptoms (primary outcome) and other outcomes more than sham,that benefit will&#xD;
      persist for 2 years after training, that initial TBR will moderate treatment response, and&#xD;
      that change in TBR will mediate response. Research Domain Criteria and EEG brain changes will&#xD;
      be explored, including relationship of TBR to clinical symptoms, executive-function&#xD;
      impairment, and sleep.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 2014</start_date>
  <completion_date type="Actual">August 2020</completion_date>
  <primary_completion_date type="Actual">April 2019</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Scores of Teacher and Parent Rated Inattentive Symptoms</measure>
    <time_frame>Assessed at Baseline, Mid-treatment (2 months), End-treatment (4 months), at 6 month follow up, at 13 month follow up</time_frame>
    <description>The primary outcome measure is the composite scores of teacher and parent-rated inattentive symptoms on the Conners-3, rated on a scale of 0-3. Lower scores represent a better outcome, with a maximum score of 3 and a minimum score of 0.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">144</enrollment>
  <condition>Attention-Deficit/Hyperactivity Disorder</condition>
  <arm_group>
    <arm_group_label>Neurofeedback treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The intended treatment is downtraining of theta power and uptraining of beta power for 38 treatments of active NF.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham neurofeedback treatment</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants assigned to sham and their trainers will be fed EEG data from pre-recorded files (recorded during live clinical NF) rather than from the participant's live signal. In order to prevent unblinding of experienced NF trainers/technicians, artifacts from the participant's EMG and EOG are blended into the pre-recorded EEG so that the trainer controlling the feedback cannot differentiate between live and simulated data. To insure trainer/technician blindness, the pre-recorded EEG will be 38 consecutive EEGs from the same age-matched clinical case so that EEGs of the sham group will also show &quot;training progress&quot; over successive sessions, like real NF.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Neurofeedback treatment</intervention_name>
    <description>Each session, the child participates in 5 training tasks. Each task lasts 5 minutes at the beginning and gradually increases to 9 minutes per task over the course of the neurofeedback as the child's attention span improves. We record four results for each of the 5 tasks:&#xD;
The number of half-second periods that they met the reward parameters (i.e. theta mV below threshold; beta mV above threshold)&#xD;
Average voltage of theta waves&#xD;
Average voltage of beta&#xD;
Average ratio of theta to beta power (TBR)</description>
    <arm_group_label>Neurofeedback treatment</arm_group_label>
    <arm_group_label>Sham neurofeedback treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Boys and girls age 7 to 10&#xD;
&#xD;
          -  IQ&gt;80&#xD;
&#xD;
          -  diagnosed DSM-5 ADHD inattentive presentation or combined presentation&#xD;
&#xD;
          -  an item mean ≥1.5 sd above norms on a 0-3 metric both on parent ratings of either&#xD;
             DSM-IV inattentive symptoms or all 18 ADHD symptoms and on teacher ratings of either&#xD;
             inattentive symptoms or all 18 ADHD symptoms&#xD;
&#xD;
          -  an eyes-open QEEG with theta-beta power ratio &gt;4.5 at Cz or Fz&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  comorbid disorder requiring psychoactive medication other than FDA-approved ADHD&#xD;
             medication&#xD;
&#xD;
          -  a medical disorder requiring systemic chronic medication with confounding psychoactive&#xD;
             effects&#xD;
&#xD;
          -  sleep apnea&#xD;
&#xD;
          -  restless legs syndrome&#xD;
&#xD;
          -  IQ &lt;80&#xD;
&#xD;
          -  plans to move requiring school change during the next 3 months&#xD;
&#xD;
          -  plans to start other ADHD treatment in the next 3 months&#xD;
&#xD;
          -  antipsychotic agent in the 6 months prior to baseline assessment&#xD;
&#xD;
          -  fluoxetine in the 4 weeks prior to baseline&#xD;
&#xD;
          -  other psychiatric medication in the two weeks prior to baseline&#xD;
&#xD;
             -&gt;5 previous NF treatments&#xD;
&#xD;
          -  Vitamin D deficiency will be a temporary exclusion&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>7 Years</minimum_age>
    <maximum_age>10 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>L. Eugene Arnold, MD, MEd</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Ohio State University Nisonger Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Roger deBeus, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of North Carolina at Asheville</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of North Carolina at Asheville</name>
      <address>
        <city>Asheville</city>
        <state>North Carolina</state>
        <zip>28804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ohio State University Nisonger Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>September 17, 2014</study_first_submitted>
  <study_first_submitted_qc>September 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 29, 2014</study_first_posted>
  <results_first_submitted>July 6, 2020</results_first_submitted>
  <results_first_submitted_qc>August 17, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">September 1, 2020</results_first_posted>
  <last_update_submitted>September 8, 2020</last_update_submitted>
  <last_update_submitted_qc>September 8, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 29, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ohio State University</investigator_affiliation>
    <investigator_full_name>L. Eugene Arnold</investigator_full_name>
    <investigator_title>Professor Emeritus of Psychiatry</investigator_title>
  </responsible_party>
  <keyword>ADHD</keyword>
  <keyword>Attention-Deficit/Hyperactivity Disorder</keyword>
  <keyword>neurofeedback</keyword>
  <keyword>EEG</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperkinesis</mesh_term>
    <mesh_term>Attention Deficit Disorder with Hyperactivity</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 5, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/43/NCT02251743/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Of 329 children screened, 305 passed categorical and parent-rated dimensional criteria for ADHD. Of these, 235 passed the TBR screen. Of the149 completely eligible,144 were randomized, and of the 144, 2 withdrew consent for logistical reasons before any post-treatment assessment. Thus,142 subjects comprised the population for the primary analysis.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Neurofeedback Treatment</title>
          <description>The intended treatment is downtraining of theta power and uptraining of beta power for 38 treatments of active NF.&#xD;
Neurofeedback treatment: Each session, the child participates in 5 training tasks. Each task lasts 5 minutes at the beginning and gradually increases to 9 minutes per task over the course of the neurofeedback as the child's attention span improves. We record four results for each of the 5 tasks:&#xD;
The number of half-second periods that they met the reward parameters (i.e. theta mV below threshold; beta mV above threshold)&#xD;
Average voltage of theta waves&#xD;
Average voltage of beta&#xD;
Average ratio of theta to beta power (TBR)</description>
        </group>
        <group group_id="P2">
          <title>Sham Neurofeedback Treatment</title>
          <description>Participants assigned to sham and their trainers will be fed EEG data from pre-recorded files (recorded during live clinical NF) rather than from the participant's live signal. In order to prevent unblinding of experienced NF trainers/technicians, artifacts from the participant's EMG and EOG are blended into the pre-recorded EEG so that the trainer controlling the feedback cannot differentiate between live and simulated data. To insure trainer/technician blindness, the pre-recorded EEG will be 38 consecutive EEGs from the same age-matched clinical case so that EEGs of the sham group will also show &quot;training progress&quot; over successive sessions, like real NF.&#xD;
Neurofeedback treatment: Each session, the child participates in 5 training tasks. Each task lasts 5 minutes at the beginning and gradually increases to 9 minutes per task over the course of the neurofeedback as the child's attention span improves. We record four results for each of the 5 tasks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="85"/>
                <participants group_id="P2" count="59"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="84"/>
                <participants group_id="P2" count="58"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Neurofeedback Treatment</title>
          <description>The intended treatment is downtraining of theta power and uptraining of beta power for 38 treatments of active NF.&#xD;
Neurofeedback treatment: Each session, the child participates in 5 training tasks. Each task lasts 5 minutes at the beginning and gradually increases to 9 minutes per task over the course of the neurofeedback as the child's attention span improves. We record four results for each of the 5 tasks:&#xD;
The number of half-second periods that they met the reward parameters (i.e. theta mV below threshold; beta mV above threshold)&#xD;
Average voltage of theta waves&#xD;
Average voltage of beta&#xD;
Average ratio of theta to beta power (TBR)</description>
        </group>
        <group group_id="B2">
          <title>Sham Neurofeedback Treatment</title>
          <description>Participants assigned to sham and their trainers will be fed EEG data from pre-recorded files (recorded during live clinical NF) rather than from the participant's live signal. In order to prevent unblinding of experienced NF trainers/technicians, artifacts from the participant's EMG and EOG are blended into the pre-recorded EEG so that the trainer controlling the feedback cannot differentiate between live and simulated data. To insure trainer/technician blindness, the pre-recorded EEG will be 38 consecutive EEGs from the same age-matched clinical case so that EEGs of the sham group will also show &quot;training progress&quot; over successive sessions, like real NF.&#xD;
Neurofeedback treatment: Each session, the child participates in 5 training tasks. Each task lasts 5 minutes at the beginning and gradually increases to 9 minutes per task over the course of the neurofeedback as the child's attention span improves. We record four results for each of the 5 tasks.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="84"/>
            <count group_id="B2" value="58"/>
            <count group_id="B3" value="142"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8.67" spread="1.1"/>
                    <measurement group_id="B2" value="8.51" spread="1.17"/>
                    <measurement group_id="B3" value="8.58" spread="1.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="65"/>
                    <measurement group_id="B2" value="46"/>
                    <measurement group_id="B3" value="111"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Hispanic/Latino</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="64"/>
                    <measurement group_id="B2" value="42"/>
                    <measurement group_id="B3" value="106"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black/African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Multi-Race</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unknown</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Primary Living Arrangement</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Parental (at least one parent)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="80"/>
                    <measurement group_id="B2" value="52"/>
                    <measurement group_id="B3" value="132"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Parental (shared custody)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Relative other than parents</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Number of Adults in Home</title>
          <units>average number of adults in home</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1.94" spread="0.61"/>
                    <measurement group_id="B2" value="2.14" spread="0.78"/>
                    <measurement group_id="B3" value="2.02" spread="0.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Number of Children in Home</title>
          <units>average number of children in home</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2.12" spread="1.03"/>
                    <measurement group_id="B2" value="2.12" spread="0.88"/>
                    <measurement group_id="B3" value="2.12" spread="0.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Primary Caregiver</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Biological Mother</title>
                  <measurement_list>
                    <measurement group_id="B1" value="67"/>
                    <measurement group_id="B2" value="49"/>
                    <measurement group_id="B3" value="116"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Biological Father</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Adoptive Mother</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Grandmother</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Child's Educational setting</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Regular public school</title>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="57"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Regular private/parochial school</title>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="57"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Regular school + special classes</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Home schooled</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Charter School</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Child's Current grade</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>1</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>2</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="38"/>
                  </measurement_list>
                </category>
                <category>
                  <title>3</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="43"/>
                  </measurement_list>
                </category>
                <category>
                  <title>4</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>5</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Repeated Grade</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Number of school changes</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>0</title>
                  <measurement_list>
                    <measurement group_id="B1" value="48"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="80"/>
                  </measurement_list>
                </category>
                <category>
                  <title>1</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="42"/>
                  </measurement_list>
                </category>
                <category>
                  <title>2 or more</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Special Education Services</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Individual Educational Plan</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>504 Plan</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Special accommodations</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>ADHD Subtype</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Inattentive</title>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="51"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Combined</title>
                  <measurement_list>
                    <measurement group_id="B1" value="53"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>ADHD Medication</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Composite Conner's Subscale (Parent and Teacher)</title>
          <description>The composited (averaged) scores of teacher and parent-rated subscales on the Conners-3 range from a scale of 0-3. Lower scores represent a better outcome.&#xD;
The impression indices range from 0-6. A higher score on these indices shows a measure of positive or negative bias on the parent/teacher report forms. For example, a higher score on the positive index shows a more positive bias in the ratings.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <title>ADHD Inattentiveness</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2" spread="0.51"/>
                    <measurement group_id="B2" value="2.08" spread="0.51"/>
                    <measurement group_id="B3" value="2.03" spread="0.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ADHD Hyperactivity-Impulsivity</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1.68" spread="0.77"/>
                    <measurement group_id="B2" value="1.88" spread="0.66"/>
                    <measurement group_id="B3" value="1.77" spread="0.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Inattentive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2.04" spread="0.52"/>
                    <measurement group_id="B2" value="2.13" spread="0.49"/>
                    <measurement group_id="B3" value="2.08" spread="0.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyperactivity-Impulsivity</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1.71" spread="0.78"/>
                    <measurement group_id="B2" value="1.92" spread="0.64"/>
                    <measurement group_id="B3" value="1.79" spread="0.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Learning Problems</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1.31" spread="0.71"/>
                    <measurement group_id="B2" value="1.18" spread="0.75"/>
                    <measurement group_id="B3" value="1.25" spread="0.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Executive Functioning</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1.9" spread="0.62"/>
                    <measurement group_id="B2" value="1.96" spread="0.58"/>
                    <measurement group_id="B3" value="1.92" spread="0.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Aggression</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0.46" spread="0.44"/>
                    <measurement group_id="B2" value="0.46" spread="0.42"/>
                    <measurement group_id="B3" value="0.46" spread="0.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Peer Relations</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0.73" spread="0.67"/>
                    <measurement group_id="B2" value="0.66" spread="0.68"/>
                    <measurement group_id="B3" value="0.7" spread="0.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Global Index</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1.49" spread="0.59"/>
                    <measurement group_id="B2" value="1.61" spread="0.5"/>
                    <measurement group_id="B3" value="1.54" spread="0.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Conduct Disorder</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0.17" spread="0.21"/>
                    <measurement group_id="B2" value="0.15" spread="0.22"/>
                    <measurement group_id="B3" value="0.16" spread="0.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Oppositional Defiant</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0.87" spread="0.67"/>
                    <measurement group_id="B2" value="0.92" spread="0.6"/>
                    <measurement group_id="B3" value="0.89" spread="0.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Positive Impression Index</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0.32" spread="0.31"/>
                    <measurement group_id="B2" value="0.33" spread="0.32"/>
                    <measurement group_id="B3" value="0.33" spread="0.31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Negative Impression Index</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0.18" spread="0.23"/>
                    <measurement group_id="B2" value="0.19" spread="0.24"/>
                    <measurement group_id="B3" value="0.18" spread="0.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>CHIPS</title>
          <description>The Child Inventory of Psychiatric Syndomes (CHIPS) Structured diagnostic interview of child and parent</description>
          <units>number of participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Oppositional-Defiant Disorder</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="41"/>
                    <measurement group_id="B2" value="30"/>
                    <measurement group_id="B3" value="71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Specific Phobias</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Generalized Anxiety Disorder</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Separation Anxiety</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Social Phobia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Scores of Teacher and Parent Rated Inattentive Symptoms</title>
        <description>The primary outcome measure is the composite scores of teacher and parent-rated inattentive symptoms on the Conners-3, rated on a scale of 0-3. Lower scores represent a better outcome, with a maximum score of 3 and a minimum score of 0.</description>
        <time_frame>Assessed at Baseline, Mid-treatment (2 months), End-treatment (4 months), at 6 month follow up, at 13 month follow up</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Neurofeedback Treatment</title>
            <description>The intended treatment is downtraining of theta power and uptraining of beta power for 38 treatments of active NF.&#xD;
Neurofeedback treatment: Each session, the child participates in 5 training tasks. Each task lasts 5 minutes at the beginning and gradually increases to 9 minutes per task over the course of the neurofeedback as the child's attention span improves. We record four results for each of the 5 tasks:&#xD;
The number of half-second periods that they met the reward parameters (i.e. theta mV below threshold; beta mV above threshold)&#xD;
Average voltage of theta waves&#xD;
Average voltage of beta&#xD;
Average ratio of theta to beta power (TBR)</description>
          </group>
          <group group_id="O2">
            <title>Sham Neurofeedback Treatment</title>
            <description>Participants assigned to sham and their trainers will be fed EEG data from pre-recorded files (recorded during live clinical NF) rather than from the participant's live signal. In order to prevent unblinding of experienced NF trainers/technicians, artifacts from the participant's EMG and EOG are blended into the pre-recorded EEG so that the trainer controlling the feedback cannot differentiate between live and simulated data. To insure trainer/technician blindness, the pre-recorded EEG will be 38 consecutive EEGs from the same age-matched clinical case so that EEGs of the sham group will also show &quot;training progress&quot; over successive sessions, like real NF.&#xD;
Neurofeedback treatment: Each session, the child participates in 5 training tasks. Each task lasts 5 minutes at the beginning and gradually increases to 9 minutes per task over the course of the neurofeedback as the child's attention span improves. We record four results for each of the 5 tasks.</description>
          </group>
        </group_list>
        <measure>
          <title>Scores of Teacher and Parent Rated Inattentive Symptoms</title>
          <description>The primary outcome measure is the composite scores of teacher and parent-rated inattentive symptoms on the Conners-3, rated on a scale of 0-3. Lower scores represent a better outcome, with a maximum score of 3 and a minimum score of 0.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="84"/>
                <count group_id="O2" value="58"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.00" spread="0.37"/>
                    <measurement group_id="O2" value="2.08" spread="0.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mid-Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.51" spread="0.49"/>
                    <measurement group_id="O2" value="1.60" spread="0.46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>End-Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.43" spread="0.51"/>
                    <measurement group_id="O2" value="1.54" spread="0.44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 month follow up</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.50" spread="0.52"/>
                    <measurement group_id="O2" value="1.52" spread="0.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>13 month follow up</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.37" spread="0.56"/>
                    <measurement group_id="O2" value="1.58" spread="0.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data were collected at every visit- from baseline, at the first session of each week, and at 13-month follow up (~1.5 years).</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Neurofeedback Treatment</title>
          <description>The intended treatment is downtraining of theta power and uptraining of beta power for 38 treatments of active NF.&#xD;
Neurofeedback treatment: Each session, the child participates in 5 training tasks. Each task lasts 5 minutes at the beginning and gradually increases to 9 minutes per task over the course of the neurofeedback as the child's attention span improves. We record four results for each of the 5 tasks:&#xD;
The number of half-second periods that they met the reward parameters (i.e. theta mV below threshold; beta mV above threshold)&#xD;
Average voltage of theta waves&#xD;
Average voltage of beta&#xD;
Average ratio of theta to beta power (TBR)</description>
        </group>
        <group group_id="E2">
          <title>Sham Neurofeedback Treatment</title>
          <description>Participants assigned to sham and their trainers will be fed EEG data from pre-recorded files (recorded during live clinical NF) rather than from the participant's live signal. In order to prevent unblinding of experienced NF trainers/technicians, artifacts from the participant's EMG and EOG are blended into the pre-recorded EEG so that the trainer controlling the feedback cannot differentiate between live and simulated data. To insure trainer/technician blindness, the pre-recorded EEG will be 38 consecutive EEGs from the same age-matched clinical case so that EEGs of the sham group will also show &quot;training progress&quot; over successive sessions, like real NF.&#xD;
Neurofeedback treatment: Each session, the child participates in 5 training tasks. Each task lasts 5 minutes at the beginning and gradually increases to 9 minutes per task over the course of the neurofeedback as the child's attention span improves. We record four results for each of the 5 tasks.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="58"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (10.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="75" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="50" subjects_at_risk="58"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Eye pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="58"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Difficulty initiating sleep</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Sleep Symptoms, NOS</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Crying</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Labile mood</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Difficulty maintaining sleep</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Self-injurious behavior</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="58"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Sedation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Tic disorders</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="58"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depressed mood</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Suicidal ideation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="58"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Social circumstances</title>
            <event_list>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Oppositionality</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Hyperactivity</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Aggression</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Impulsivity</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Behavioral, NOS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="58"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>This study tested only one of the standard ADHD protocols, theta-beta NF. Results cannot be generalized to the other standard protocols of slow cortical potential (SCP) and sensory-motor rhythm (SMR) neurofeedback, nor fMRI neurofeedback.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. L Eugene Arnold</name_or_title>
      <organization>Ohio State University</organization>
      <phone>614-685-6701</phone>
      <email>L.Arnold@osumc.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02251743
org study id: 2013H0417
secondary id: 1R01MH100144-01A1
nct id: NCT02251743
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
Additional treatments with long-term benefit for attention-deficit/hyperactivity disorder
      (ADHD) are needed; one of the more promising is neurofeedback (EEG biofeedback), which has
      several randomized controlled trials showing significant benefit, but which are inconclusive
      because they were not double-blinded; the benefit could have been nonspecific (placebo
      response). Because of neurofeedback's labor-intensive cost (1 treatment costing as much as a
      month's medication), It is important to know how much specific benefit it yields. This 2-
      site placebo-controlled double-blind randomized clinical trial is the first to test for a
      specific benefit of neurofeedback with adequate power, the first designed and implemented
      collaboratively by experts in neurofeedback, ADHD, and clinical trials, the first to
      rigorously monitor quality not only of treatment, but also of placebo and blinding, and the
      first to follow up for 2 years to examine enduring effect; the results, whether positive or
      negative, will provide evidence for clinical practice and public policy regarding ADHD.
Current established, evidence-based treatments for attention-deficit/hyperactivity disorder
      (ADHD) are incompletely effective and not universally acceptable, and appear to wane in
      effect over time despite significant immediate benefit. E.g., FDA-approved medication, which
      shows large acute benefit, leaves a third of children only partially treated even when
      combined with behavioral treatment, and has not been demonstrated effective beyond 2 years.
      Additional treatments are needed that are effective with persisting benefit, preferably
      related to a biomarker predicting treatment response. A good candidate is
      electroencephalographic (EEG) biofeedback, called neurofeedback (NF). It is based on 1)
      observations that patients with ADHD often have excessive theta band (4-8 Hz) quantitative
      EEG power, low beta band (13-21 Hz) power, and excessive theta beta ratio (TBR), and 2)
      theoretical application of operant conditioning to correct this EEG imbalance. Metaanalysis
      of 6 randomized clinical trials found a large benefit for inattentive symptoms and medium
      benefit for hyperactive-impulsive symptoms. Unfortunately, none of these were blinded. Three
      of 4 small blinded studies found no advantage for NF over sham, but used suboptimal NF,
      leaving the situation inconclusive. Because of the expense and time required by NF, there is
      a public health need to determine whether it has a specific effect beyond the obvious
      nonspecific benefit of doing a focused activity several times a week with a
      friendly,encouraging adult who reinforces for attending to the task. Experts in NF, ADHD,
      clinical trials, statistics, and data management have joined to design a double-blind
      sham-controlled randomized clinical trial to answer several pressing scientific and clinical
      questions in a way that will be credible to all. At each of 2 sites (1 university & 1 NF
      clinic) 70 children (total N=140) age 7 through 10 with rigorously diagnosed moderate to
      severe ADHD and TBR>5 will be randomized in a 3:2 ratio to active TBR downtraining by NF vs.
      a sham training of equal duration, intensity, and appearance. To keep both participants and
      study staff blind, the sham will utilize pre-recorded EEGs with the participant's artifacts
      superimposed. The sham will be programmed into the equipment via internet by an off-site
      statistician-guided person who has no contact with participants. Treatment fidelity will be
      trained and monitored by 2 acknowledged NF leaders in a manner that protects blinding.
      Multi-domain assessments at baseline, mid-treatment, treatment end, and follow-ups at 6
      months, 1 year, and 2 years will include parent and teacher ratings of symptoms & impairment,
      neuropsychological tests,clinician ratings, and quantitative EEG as well as tests of blinding
      and of sham inertness. Hypotheses include that NF will improve parent- and teacher-rated
      inattentive symptoms (primary outcome) and other outcomes more than sham,that benefit will
      persist for 2 years after training, that initial TBR will moderate treatment response, and
      that change in TBR will mediate response. Research Domain Criteria and EEG brain changes will
      be explored, including relationship of TBR to clinical symptoms, executive-function
      impairment, and sleep.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Scores of Teacher and Parent Rated Inattentive Symptoms
time frame: Assessed at Baseline, Mid-treatment (2 months), End-treatment (4 months), at 6 month follow up, at 13 month follow up
description: The primary outcome measure is the composite scores of teacher and parent-rated inattentive symptoms on the Conners-3, rated on a scale of 0-3. Lower scores represent a better outcome, with a maximum score of 3 and a minimum score of 0.
arm group label: Neurofeedback treatment
arm group type: Experimental
description: The intended treatment is downtraining of theta power and uptraining of beta power for 38 treatments of active NF.
arm group label: Sham neurofeedback treatment
arm group type: Placebo Comparator
description: Participants assigned to sham and their trainers will be fed EEG data from pre-recorded files (recorded during live clinical NF) rather than from the participant's live signal. In order to prevent unblinding of experienced NF trainers/technicians, artifacts from the participant's EMG and EOG are blended into the pre-recorded EEG so that the trainer controlling the feedback cannot differentiate between live and simulated data. To insure trainer/technician blindness, the pre-recorded EEG will be 38 consecutive EEGs from the same age-matched clinical case so that EEGs of the sham group will also show "training progress" over successive sessions, like real NF.
intervention type: Device
intervention name: Neurofeedback treatment
description: Each session, the child participates in 5 training tasks. Each task lasts 5 minutes at the beginning and gradually increases to 9 minutes per task over the course of the neurofeedback as the child's attention span improves. We record four results for each of the 5 tasks:
The number of half-second periods that they met the reward parameters (i.e. theta mV below threshold; beta mV above threshold)
Average voltage of theta waves
Average voltage of beta
Average ratio of theta to beta power (TBR)
arm group label: Neurofeedback treatment
arm group label: Sham neurofeedback treatment
criteria: 
gender: All
minimum age: 7 Years
maximum age: 10 Years
healthy volunteers: No
last name: L. Eugene Arnold, MD, MEd
role: Principal Investigator
affiliation: The Ohio State University Nisonger Center
last name: Roger deBeus, Ph.D.
role: Principal Investigator
affiliation: University of North Carolina at Asheville
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Ohio State University
investigator full name: L. Eugene Arnold
investigator title: Professor Emeritus of Psychiatry
mesh term: Hyperkinesis
mesh term: Attention Deficit Disorder with Hyperactivity
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: This study tested only one of the standard ADHD protocols, theta-beta NF. Results cannot be generalized to the other standard protocols of slow cortical potential (SCP) and sensory-motor rhythm (SMR) neurofeedback, nor fMRI neurofeedback.
point of contact: 