<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/NCT03008889</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00088115</org_study_id>
    <nct_id>NCT03008889</nct_id>
  </id_info>
  <brief_title>A Feasibility Study of N-acetylcysteine for Self-injurious Behavior in Children With Autism Spectrum Disorder</brief_title>
  <acronym>NAC</acronym>
  <official_title>A Feasibility Study of N-acetylcysteine for Self-injurious Behavior in Children With Autism Spectrum Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Emory University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Emory University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to demonstrate the feasibility of a 9-week, randomized trial of&#xD;
      N-acetylcysteine (NAC) compared to placebo in 14 children (age 5 to 12 years) with Autism&#xD;
      Spectrum Disorder (ASD) and a moderate level of repetitive self-injurious behavior (SIB).&#xD;
      Additional aims are to evaluate the positive predictive value of a screening method to&#xD;
      classify children with automatically maintained self-injurious behavior; to evaluate the&#xD;
      preliminary efficacy of NAC for reducing repetitive SIB in children with ASD; and to evaluate&#xD;
      biomarkers and possible mechanisms of action of NAC in children with ASD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Self-injurious behavior (SIB) in children with autism spectrum disorder (ASD) can cause&#xD;
      physical harm to the child and interfere with the child's ability to make use of educational&#xD;
      programs and helpful treatments such as speech therapy. The turmoil caused by self-injurious&#xD;
      behaviors in children with ASD invariably interferes with daily routines because family life&#xD;
      often stops during these episodes and family members worry about setting off SIB between&#xD;
      episodes. This project will use the detailed assessment methods developed in the field of&#xD;
      behavior therapy to evaluate the potential for N-acetylcysteine (NAC) to treat children with&#xD;
      ASD and moderate repetitive SIB. NAC is an over-the-counter dietary supplement that may have&#xD;
      beneficial effects on the brain through its well-documented antioxidant effects and/or&#xD;
      reduced glutamate signaling. In the proposed study, 14 children with ASD and repetitive SIB&#xD;
      between the ages of 5 and 12 will be randomly assigned to gradually increasing doses of NAC&#xD;
      or placebo for 9 weeks. The research team, parents and children will be blind to the&#xD;
      treatment with NAC or placebo. Participants will come to the research site periodically to&#xD;
      complete measures and behavioral assessments.&#xD;
&#xD;
      After the 9 weeks of treatment, children randomized to NAC who showed improvement will be&#xD;
      encouraged to continue taking the supplement outside the study. Children who were randomly&#xD;
      assigned to the placebo and showed no improvement will be offered open-label treatment with&#xD;
      NAC. Children who did not improve while taking NAC or those who improved while on the placebo&#xD;
      will be advised on next steps by the study team.&#xD;
&#xD;
      The goal of this feasibility study is establish the acceptability viability of study&#xD;
      procedures in this vulnerable population, to learn about the potential benefits and adverse&#xD;
      effects of NAC. Demonstrating these feasibility aims and the preliminary efficacy and safety&#xD;
      of NAC is a prerequisite for planning a larger, more definitive, study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 5, 2018</start_date>
  <completion_date type="Actual">September 12, 2019</completion_date>
  <primary_completion_date type="Actual">September 12, 2019</primary_completion_date>
  <phase>Phase 2</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>Percentage of Participants Randomized</measure>
    <time_frame>12 months (throughout the duration of the study)</time_frame>
    <description>Goal: randomize 1.75 participants per month</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Attrition Rate</measure>
    <time_frame>12 months (throughout the duration of the study)</time_frame>
    <description>Attrition rate is defined as the percent of subjects who did not complete the study. Goal:less than 15% (to indicate that study was acceptable to participants and parents).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Study Medication Compliance</measure>
    <time_frame>12 months (throughout the duration of the study)</time_frame>
    <description>Goal: at least 70% treatment compliance (tablet counts and drug dairies).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Successful Collection of Outcome Measures</measure>
    <time_frame>12 months (throughout the duration of the study)</time_frame>
    <description>Goal: at least 80% collection of essential outcome data to demonstrate the feasibility of data collection procedures.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Parent Satisfaction Rating</measure>
    <time_frame>Week 9 (at the end of the study intervention)</time_frame>
    <description>Goal: at least 80% of parents will agree or strongly agree when asked in an anonymous survey that they would recommend the study and the study treatment to other parents of children with ASD and SIB.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Positive Predictive Value of Screening Method of Classifying Self-injurious Behavior (SIB) by Type.</measure>
    <time_frame>12 months (duration of the study)</time_frame>
    <description>Goal: at least 75% positive predictive value of our screening method to classify children with automatically maintained self-injurious behavior using a semi-structured interview at screening compared to the findings of five- to six-hour functional analysis at baseline. Only children who appear to have automatically maintained SIB will be referred for the baseline evaluation.&#xD;
Demonstrating a high positive predictive value for the screening method is a necessary prerequisite for launching a larger study. Using the formula: Positive Predictive Value (PPV) = screen positive and true cases ÷ all positive screens, a value of 75% or greater would indicate success of the screening method used.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Aberrant Behavior Checklist Irritability Subscale Score at Baseline and 9 Weeks Post-intervention</measure>
    <time_frame>Baseline, Week 9</time_frame>
    <description>The Aberrant Behavior Checklist (ABC) is a commonly used 58-item parent-rated measure of overall behavioral problems. The Irritability subscale is comprised of 15 items reflecting tantrums, aggression and self injury. Range is 0 to 45, higher scores indicate higher severity. As a preliminary efficacy outcome, it was calculated the average score at baseline and Week 9 post-intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Self-Injurious Behavior Events</measure>
    <time_frame>Baseline, Week 9</time_frame>
    <description>Direct observation of the frequency of SIB was collected at baseline in a separate observational session after completing the functional analysis and again at Week 9. Investigators set a benchmark of an average decline in the frequency of SIB of 50% within the NAC group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Clinical Global Impression (CGI-I) Scale at 9 Weeks Post-intervention</measure>
    <time_frame>Week 9</time_frame>
    <description>The Clinical Global Impression (CGI-I) scale is a 7-item scale from 1 (Very Much Improved) through 4 (No Change) to 7 (Very Much Worse). By convention, scores of 2 (Much Improved) or 1 (Very Much Improved) are used to define positive response.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Biomarkers and Possible Mechanisms of Action of NAC in Children With ASD.</measure>
    <time_frame>Baseline, Week 9</time_frame>
    <description>Changes amino acid levels before and after NAC treatment: cysteine/cystine and glutathione/glutathione disulfide (GSH/GSSG) ratios (antioxidant effects), glutamate and glutamate/glutamine ratio (glutamate signaling) and GABA levels.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Autism Spectrum Disorder</condition>
  <arm_group>
    <arm_group_label>Participants taking NAC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants randomized to the active treatment study arm will receive gradually increasing doses of N-acetylcysteine (NAC) given as a dissolving tablet in juice or water. NAC is an over-the-counter oral dietary supplement that will be used a higher than usual doses in this study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Participants taking Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants randomized to placebo will receive dissolving tablets identical in size and appearance to the active treatment. Placebo capsules contain inactive ingredients.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>N-acetylcysteine</intervention_name>
    <description>Participants will start with taking 900mg of NAC once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects will return to the study site to review adverse events.&#xD;
In the absence of dose limiting adverse events attributable to the study drug, the dose will be gradually increased to 900 mg twice per day for study days 8-28.&#xD;
If this dose is well-tolerated, the dose will be increased to 900 three times per day for study days 29-63.</description>
    <arm_group_label>Participants taking NAC</arm_group_label>
    <other_name>NAC</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Participants will start with taking 900mg of the placebo once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects will return to the study site to review adverse events. The dosing for the placebo will increase in the same fashion as the active treatment.&#xD;
In the absence of dose limiting adverse events attributable to the study drug, the dose will be gradually increased to 900 mg twice per day for study days 8-28.&#xD;
If this dose is well-tolerated, the dose will be increased to 900 three times per day for study days 29-63.</description>
    <arm_group_label>Participants taking Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Confirmed diagnosis of Autism Spectrum Disorder (ASD)&#xD;
&#xD;
          -  Confirmed presence of moderate Self Injurious Behavior (SIB)&#xD;
&#xD;
          -  Score &gt; 16 on the parent-rated Aberrant Behavior Checklist Irritability subscale&#xD;
             (moderate level of disruptive behavior)&#xD;
&#xD;
          -  Classified as having automatically maintained SIB (determined during screening by a&#xD;
             detailed functional analysis)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  On a stable medication dose for less than 4 weeks&#xD;
&#xD;
          -  Planned change in medication during the 9-week trial&#xD;
&#xD;
          -  Had one or more seizures in the last 6 months&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>5 Years</minimum_age>
    <maximum_age>12 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lawrence Scahill, MSN, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Emory University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Marcus Autism Center</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30329</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>December 28, 2016</study_first_submitted>
  <study_first_submitted_qc>December 30, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 4, 2017</study_first_posted>
  <results_first_submitted>September 4, 2020</results_first_submitted>
  <results_first_submitted_qc>November 19, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">December 16, 2020</results_first_posted>
  <last_update_submitted>January 7, 2021</last_update_submitted>
  <last_update_submitted_qc>January 7, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 26, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Emory University</investigator_affiliation>
    <investigator_full_name>Lawrence Scahill, MSN, PhD</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Repetitive Self-Injurious Behavior</keyword>
  <keyword>N-acetylcysteine (NAC)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Autistic Disorder</mesh_term>
    <mesh_term>Autism Spectrum Disorder</mesh_term>
    <mesh_term>Child Development Disorders, Pervasive</mesh_term>
    <mesh_term>Self-Injurious Behavior</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acetylcysteine</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>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 18, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/89/NCT03008889/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>There were eight consented (or enrolled) participants. Out of the eight participants, one screened failed early, and seven subjects were eligible for the Screening method for classifying self-injurious behavior (SIB) before randomization. Out of those seven, 3 passed screening, and one of the 3 withdrew due to study burden. Two participants were randomized to an intervention (NAC or placebo).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Participants Taking NAC</title>
          <description>Participants randomized to the active treatment study arm will receive gradually increasing doses of N-acetylcysteine (NAC) given as a dissolving tablet in juice or water. NAC is an over-the-counter oral dietary supplement that will be used a higher than usual doses in this study.&#xD;
N-acetylcysteine: Participants will start with taking 900mg of NAC once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects will return to the study site to review adverse events.&#xD;
In the absence of dose limiting adverse events attributable to the study drug, the dose will be gradually increased to 900 mg twice per day for study days 8-28.&#xD;
If this dose is well-tolerated, the dose will be increased to 900 three times per day for study days 29-63.</description>
        </group>
        <group group_id="P2">
          <title>Participants Taking Placebo</title>
          <description>Participants randomized to placebo will receive dissolving tablets identical in size and appearance to the active treatment. Placebo capsules contain inactive ingredients.&#xD;
Placebo: Participants will start with taking 900mg of the placebo once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects will return to the study site to review adverse events. The dosing for the placebo will increase in the same fashion as the active treatment.&#xD;
In the absence of dose limiting adverse events attributable to the study drug, the dose will be gradually increased to 900 mg twice per day for study days 8-28.&#xD;
If this dose is well-tolerated, the dose will be increased to 900 three times per day for study days 29-63.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Participants Taking NAC</title>
          <description>Participants randomized to the active treatment study arm will receive gradually increasing doses of N-acetylcysteine (NAC) given as a dissolving tablet in juice or water. NAC is an over-the-counter oral dietary supplement that will be used a higher than usual doses in this study.&#xD;
N-acetylcysteine: Participants will start with taking 900mg of NAC once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects will return to the study site to review adverse events.&#xD;
In the absence of dose limiting adverse events attributable to the study drug, the dose will be gradually increased to 900 mg twice per day for study days 8-28.&#xD;
If this dose is well-tolerated, the dose will be increased to 900 three times per day for study days 29-63.</description>
        </group>
        <group group_id="B2">
          <title>Participants Taking Placebo</title>
          <description>Participants randomized to placebo will receive dissolving tablets identical in size and appearance to the active treatment. Placebo capsules contain inactive ingredients.&#xD;
Placebo: Participants will start with taking 900mg of the placebo once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects will return to the study site to review adverse events. The dosing for the placebo will increase in the same fashion as the active treatment.&#xD;
In the absence of dose limiting adverse events attributable to the study drug, the dose will be gradually increased to 900 mg twice per day for study days 8-28.&#xD;
If this dose is well-tolerated, the dose will be increased to 900 three times per day for study days 29-63.</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="1"/>
            <count group_id="B2" value="1"/>
            <count group_id="B3" value="2"/>
          </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" spread="0"/>
                    <measurement group_id="B2" value="9" spread="0"/>
                    <measurement group_id="B3" value="8.5" spread="0"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</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>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</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>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</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>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <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_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants Randomized</title>
        <description>Goal: randomize 1.75 participants per month</description>
        <time_frame>12 months (throughout the duration of the study)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Participants Taking NAC</title>
            <description>Participants randomized to the active treatment study arm received gradually increasing doses of N-acetylcysteine (NAC) given as a dissolving tablet in juice or water. NAC is an over-the-counter oral dietary supplement that was used at a higher than usual doses in this study.&#xD;
N-acetylcysteine: Participants started taking 900mg of NAC once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events.&#xD;
In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28.&#xD;
If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.</description>
          </group>
          <group group_id="O2">
            <title>Participants Taking Placebo</title>
            <description>Participants randomized to placebo received dissolving tablets identical in size and appearance to the active treatment. Placebo capsules contained inactive ingredients.&#xD;
Placebo: Participants started taking 900mg of the placebo once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events. The dosing for the placebo was increased in the same fashion as the active treatment.&#xD;
In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28.&#xD;
If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Randomized</title>
          <description>Goal: randomize 1.75 participants per month</description>
          <units>percentage of participants randomized</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100"/>
                    <measurement group_id="O2" value="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Attrition Rate</title>
        <description>Attrition rate is defined as the percent of subjects who did not complete the study. Goal:less than 15% (to indicate that study was acceptable to participants and parents).</description>
        <time_frame>12 months (throughout the duration of the study)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Participants Taking NAC</title>
            <description>Participants randomized to the active treatment study arm received gradually increasing doses of N-acetylcysteine (NAC) given as a dissolving tablet in juice or water. NAC is an over-the-counter oral dietary supplement that was used at a higher than usual doses in this study.&#xD;
N-acetylcysteine: Participants started taking 900mg of NAC once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events.&#xD;
In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28.&#xD;
If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.</description>
          </group>
          <group group_id="O2">
            <title>Participants Taking Placebo</title>
            <description>Participants randomized to placebo received dissolving tablets identical in size and appearance to the active treatment. Placebo capsules contained inactive ingredients.&#xD;
Placebo: Participants started taking 900mg of the placebo once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events. The dosing for the placebo was increased in the same fashion as the active treatment.&#xD;
In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28.&#xD;
If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.</description>
          </group>
        </group_list>
        <measure>
          <title>Attrition Rate</title>
          <description>Attrition rate is defined as the percent of subjects who did not complete the study. Goal:less than 15% (to indicate that study was acceptable to participants and parents).</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Study Medication Compliance</title>
        <description>Goal: at least 70% treatment compliance (tablet counts and drug dairies).</description>
        <time_frame>12 months (throughout the duration of the study)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Participants Taking NAC</title>
            <description>Participants randomized to the active treatment study arm received gradually increasing doses of N-acetylcysteine (NAC) given as a dissolving tablet in juice or water. NAC is an over-the-counter oral dietary supplement that was used at a higher than usual doses in this study.&#xD;
N-acetylcysteine: Participants started taking 900mg of NAC once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events.&#xD;
In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28.&#xD;
If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.</description>
          </group>
          <group group_id="O2">
            <title>Participants Taking Placebo</title>
            <description>Participants randomized to placebo received dissolving tablets identical in size and appearance to the active treatment. Placebo capsules contained inactive ingredients.&#xD;
Placebo: Participants started taking 900mg of the placebo once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events. The dosing for the placebo was increased in the same fashion as the active treatment.&#xD;
In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28.&#xD;
If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.</description>
          </group>
        </group_list>
        <measure>
          <title>Study Medication Compliance</title>
          <description>Goal: at least 70% treatment compliance (tablet counts and drug dairies).</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Successful Collection of Outcome Measures</title>
        <description>Goal: at least 80% collection of essential outcome data to demonstrate the feasibility of data collection procedures.</description>
        <time_frame>12 months (throughout the duration of the study)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Participants Taking NAC</title>
            <description>Participants randomized to the active treatment study arm received gradually increasing doses of N-acetylcysteine (NAC) given as a dissolving tablet in juice or water. NAC is an over-the-counter oral dietary supplement that was used at a higher than usual doses in this study.&#xD;
N-acetylcysteine: Participants started taking 900mg of NAC once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events.&#xD;
In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28.&#xD;
If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.</description>
          </group>
          <group group_id="O2">
            <title>Participants Taking Placebo</title>
            <description>Participants randomized to placebo received dissolving tablets identical in size and appearance to the active treatment. Placebo capsules contained inactive ingredients.&#xD;
Placebo: Participants started taking 900mg of the placebo once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events. The dosing for the placebo was increased in the same fashion as the active treatment.&#xD;
In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28.&#xD;
If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.</description>
          </group>
        </group_list>
        <measure>
          <title>Successful Collection of Outcome Measures</title>
          <description>Goal: at least 80% collection of essential outcome data to demonstrate the feasibility of data collection procedures.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Parent Satisfaction Rating</title>
        <description>Goal: at least 80% of parents will agree or strongly agree when asked in an anonymous survey that they would recommend the study and the study treatment to other parents of children with ASD and SIB.</description>
        <time_frame>Week 9 (at the end of the study intervention)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Participants Taking NAC</title>
            <description>Participants randomized to the active treatment study arm received gradually increasing doses of N-acetylcysteine (NAC) given as a dissolving tablet in juice or water. NAC is an over-the-counter oral dietary supplement that was used at a higher than usual doses in this study.&#xD;
N-acetylcysteine: Participants started taking 900mg of NAC once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events.&#xD;
In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28.&#xD;
If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.</description>
          </group>
          <group group_id="O2">
            <title>Participants Taking Placebo</title>
            <description>Participants randomized to placebo received dissolving tablets identical in size and appearance to the active treatment. Placebo capsules contained inactive ingredients.&#xD;
Placebo: Participants started taking 900mg of the placebo once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events. The dosing for the placebo was increased in the same fashion as the active treatment.&#xD;
In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28.&#xD;
If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.</description>
          </group>
        </group_list>
        <measure>
          <title>Parent Satisfaction Rating</title>
          <description>Goal: at least 80% of parents will agree or strongly agree when asked in an anonymous survey that they would recommend the study and the study treatment to other parents of children with ASD and SIB.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Positive Predictive Value of Screening Method of Classifying Self-injurious Behavior (SIB) by Type.</title>
        <description>Goal: at least 75% positive predictive value of our screening method to classify children with automatically maintained self-injurious behavior using a semi-structured interview at screening compared to the findings of five- to six-hour functional analysis at baseline. Only children who appear to have automatically maintained SIB will be referred for the baseline evaluation.&#xD;
Demonstrating a high positive predictive value for the screening method is a necessary prerequisite for launching a larger study. Using the formula: Positive Predictive Value (PPV) = screen positive and true cases ÷ all positive screens, a value of 75% or greater would indicate success of the screening method used.</description>
        <time_frame>12 months (duration of the study)</time_frame>
        <population>Screening method for classifying self-injurious behavior (SIB) happened before randomization. Of the 8 participants that consented, one was excluded due to asthma. Results show participants that were classified with repetitive SIB.</population>
        <group_list>
          <group group_id="O1">
            <title>Consented Participants Before Randomization</title>
            <description>Participants consented in the trial, before randomization.</description>
          </group>
        </group_list>
        <measure>
          <title>Positive Predictive Value of Screening Method of Classifying Self-injurious Behavior (SIB) by Type.</title>
          <description>Goal: at least 75% positive predictive value of our screening method to classify children with automatically maintained self-injurious behavior using a semi-structured interview at screening compared to the findings of five- to six-hour functional analysis at baseline. Only children who appear to have automatically maintained SIB will be referred for the baseline evaluation.&#xD;
Demonstrating a high positive predictive value for the screening method is a necessary prerequisite for launching a larger study. Using the formula: Positive Predictive Value (PPV) = screen positive and true cases ÷ all positive screens, a value of 75% or greater would indicate success of the screening method used.</description>
          <population>Screening method for classifying self-injurious behavior (SIB) happened before randomization. Of the 8 participants that consented, one was excluded due to asthma. Results show participants that were classified with repetitive SIB.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Aberrant Behavior Checklist Irritability Subscale Score at Baseline and 9 Weeks Post-intervention</title>
        <description>The Aberrant Behavior Checklist (ABC) is a commonly used 58-item parent-rated measure of overall behavioral problems. The Irritability subscale is comprised of 15 items reflecting tantrums, aggression and self injury. Range is 0 to 45, higher scores indicate higher severity. As a preliminary efficacy outcome, it was calculated the average score at baseline and Week 9 post-intervention.</description>
        <time_frame>Baseline, Week 9</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Participants Taking NAC</title>
            <description>Participants randomized to the active treatment study arm received gradually increasing doses of N-acetylcysteine (NAC) given as a dissolving tablet in juice or water. NAC is an over-the-counter oral dietary supplement that was used at a higher than usual doses in this study.&#xD;
N-acetylcysteine: Participants started taking 900mg of NAC once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events.&#xD;
In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28.&#xD;
If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.</description>
          </group>
          <group group_id="O2">
            <title>Participants Taking Placebo</title>
            <description>Participants randomized to placebo received dissolving tablets identical in size and appearance to the active treatment. Placebo capsules contained inactive ingredients.&#xD;
Placebo: Participants started taking 900mg of the placebo once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events. The dosing for the placebo was increased in the same fashion as the active treatment.&#xD;
In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28.&#xD;
If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.</description>
          </group>
        </group_list>
        <measure>
          <title>Aberrant Behavior Checklist Irritability Subscale Score at Baseline and 9 Weeks Post-intervention</title>
          <description>The Aberrant Behavior Checklist (ABC) is a commonly used 58-item parent-rated measure of overall behavioral problems. The Irritability subscale is comprised of 15 items reflecting tantrums, aggression and self injury. Range is 0 to 45, higher scores indicate higher severity. As a preliminary efficacy outcome, it was calculated the average score at baseline and Week 9 post-intervention.</description>
          <units>score on a scale</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Score at Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31"/>
                    <measurement group_id="O2" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Score at 9-Weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23"/>
                    <measurement group_id="O2" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Self-Injurious Behavior Events</title>
        <description>Direct observation of the frequency of SIB was collected at baseline in a separate observational session after completing the functional analysis and again at Week 9. Investigators set a benchmark of an average decline in the frequency of SIB of 50% within the NAC group.</description>
        <time_frame>Baseline, Week 9</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Participants Taking NAC</title>
            <description>Participants randomized to the active treatment study arm received gradually increasing doses of N-acetylcysteine (NAC) given as a dissolving tablet in juice or water. NAC is an over-the-counter oral dietary supplement that was used at a higher than usual doses in this study.&#xD;
N-acetylcysteine: Participants started taking 900mg of NAC once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events.&#xD;
In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28.&#xD;
If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.</description>
          </group>
          <group group_id="O2">
            <title>Participants Taking Placebo</title>
            <description>Participants randomized to placebo received dissolving tablets identical in size and appearance to the active treatment. Placebo capsules contained inactive ingredients.&#xD;
Placebo: Participants started taking 900mg of the placebo once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events. The dosing for the placebo was increased in the same fashion as the active treatment.&#xD;
In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28.&#xD;
If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Self-Injurious Behavior Events</title>
          <description>Direct observation of the frequency of SIB was collected at baseline in a separate observational session after completing the functional analysis and again at Week 9. Investigators set a benchmark of an average decline in the frequency of SIB of 50% within the NAC group.</description>
          <units>Self injurious events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="219"/>
                    <measurement group_id="O2" value="93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>9-Weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="59"/>
                    <measurement group_id="O2" value="655"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Clinical Global Impression (CGI-I) Scale at 9 Weeks Post-intervention</title>
        <description>The Clinical Global Impression (CGI-I) scale is a 7-item scale from 1 (Very Much Improved) through 4 (No Change) to 7 (Very Much Worse). By convention, scores of 2 (Much Improved) or 1 (Very Much Improved) are used to define positive response.</description>
        <time_frame>Week 9</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Participants Taking NAC</title>
            <description>Participants randomized to the active treatment study arm received gradually increasing doses of N-acetylcysteine (NAC) given as a dissolving tablet in juice or water. NAC is an over-the-counter oral dietary supplement that was used at a higher than usual doses in this study.&#xD;
N-acetylcysteine: Participants started taking 900mg of NAC once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events.&#xD;
In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28.&#xD;
If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.</description>
          </group>
          <group group_id="O2">
            <title>Participants Taking Placebo</title>
            <description>Participants randomized to placebo received dissolving tablets identical in size and appearance to the active treatment. Placebo capsules contained inactive ingredients.&#xD;
Placebo: Participants started taking 900mg of the placebo once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events. The dosing for the placebo was increased in the same fashion as the active treatment.&#xD;
In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28.&#xD;
If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Clinical Global Impression (CGI-I) Scale at 9 Weeks Post-intervention</title>
          <description>The Clinical Global Impression (CGI-I) scale is a 7-item scale from 1 (Very Much Improved) through 4 (No Change) to 7 (Very Much Worse). By convention, scores of 2 (Much Improved) or 1 (Very Much Improved) are used to define positive response.</description>
          <units>score on a scale</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Biomarkers and Possible Mechanisms of Action of NAC in Children With ASD.</title>
        <description>Changes amino acid levels before and after NAC treatment: cysteine/cystine and glutathione/glutathione disulfide (GSH/GSSG) ratios (antioxidant effects), glutamate and glutamate/glutamine ratio (glutamate signaling) and GABA levels.</description>
        <time_frame>Baseline, Week 9</time_frame>
        <population>Blood samples were collected and processed in accordance with the protocol. In consultation with our biochemist collaborator, we did not proceed with the multiple laboratory procedures to analyze the sample. Our collaborator indicated that the findings would not be interpretable because we only had two subjects.</population>
        <group_list>
          <group group_id="O1">
            <title>Participants Taking NAC</title>
            <description>Participants randomized to the active treatment study arm received gradually increasing doses of N-acetylcysteine (NAC) given as a dissolving tablet in juice or water. NAC is an over-the-counter oral dietary supplement that was used at a higher than usual doses in this study.&#xD;
N-acetylcysteine: Participants started taking 900mg of NAC once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events.&#xD;
In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28.&#xD;
If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.</description>
          </group>
          <group group_id="O2">
            <title>Participants Taking Placebo</title>
            <description>Participants randomized to placebo received dissolving tablets identical in size and appearance to the active treatment. Placebo capsules contained inactive ingredients.&#xD;
Placebo: Participants started taking 900mg of the placebo once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events. The dosing for the placebo was increased in the same fashion as the active treatment.&#xD;
In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28.&#xD;
If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Biomarkers and Possible Mechanisms of Action of NAC in Children With ASD.</title>
          <description>Changes amino acid levels before and after NAC treatment: cysteine/cystine and glutathione/glutathione disulfide (GSH/GSSG) ratios (antioxidant effects), glutamate and glutamate/glutamine ratio (glutamate signaling) and GABA levels.</description>
          <population>Blood samples were collected and processed in accordance with the protocol. In consultation with our biochemist collaborator, we did not proceed with the multiple laboratory procedures to analyze the sample. Our collaborator indicated that the findings would not be interpretable because we only had two subjects.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>9 weeks</time_frame>
      <desc>Each subject was followed by two blinded clinicians. A treating clinician who monitored adverse events and managed the dose of the study medication. An independent evaluator assessed therapeutic response and did not discuss adverse events or medication dose with parent and child.</desc>
      <group_list>
        <group group_id="E1">
          <title>Participants Taking NAC</title>
          <description>Participants randomized to the active treatment study arm will receive gradually increasing doses of N-acetylcysteine (NAC) given as a dissolving tablet in juice or water. NAC is an over-the-counter oral dietary supplement that will be used a higher than usual doses in this study.&#xD;
N-acetylcysteine: Participants will start with taking 900mg of NAC once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects will return to the study site to review adverse events.&#xD;
In the absence of dose limiting adverse events attributable to the study drug, the dose will be gradually increased to 900 mg twice per day for study days 8-28.&#xD;
If this dose is well-tolerated, the dose will be increased to 900 three times per day for study days 29-63.</description>
        </group>
        <group group_id="E2">
          <title>Participants Taking Placebo</title>
          <description>Participants randomized to placebo will receive dissolving tablets identical in size and appearance to the active treatment. Placebo capsules contain inactive ingredients.&#xD;
Placebo: Participants will start with taking 900mg of the placebo once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects will return to the study site to review adverse events. The dosing for the placebo will increase in the same fashion as the active treatment.&#xD;
In the absence of dose limiting adverse events attributable to the study drug, the dose will be gradually increased to 900 mg twice per day for study days 8-28.&#xD;
If this dose is well-tolerated, the dose will be increased to 900 three times per day for study days 29-63.</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="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="1" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Increased Appetite</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Early morning awakening</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Drowsiness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Weight gain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Aggression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Eczema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>
    <point_of_contact>
      <name_or_title>Dr. Lawrence Scahill</name_or_title>
      <organization>Emory University</organization>
      <phone>404-785-9336</phone>
      <email>lawrence.scahill@emory.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/NCT03008889
org study id: IRB00088115
nct id: NCT03008889
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to demonstrate the feasibility of a 9-week, randomized trial of
      N-acetylcysteine (NAC) compared to placebo in 14 children (age 5 to 12 years) with Autism
      Spectrum Disorder (ASD) and a moderate level of repetitive self-injurious behavior (SIB).
      Additional aims are to evaluate the positive predictive value of a screening method to
      classify children with automatically maintained self-injurious behavior; to evaluate the
      preliminary efficacy of NAC for reducing repetitive SIB in children with ASD; and to evaluate
      biomarkers and possible mechanisms of action of NAC in children with ASD.
Self-injurious behavior (SIB) in children with autism spectrum disorder (ASD) can cause
      physical harm to the child and interfere with the child's ability to make use of educational
      programs and helpful treatments such as speech therapy. The turmoil caused by self-injurious
      behaviors in children with ASD invariably interferes with daily routines because family life
      often stops during these episodes and family members worry about setting off SIB between
      episodes. This project will use the detailed assessment methods developed in the field of
      behavior therapy to evaluate the potential for N-acetylcysteine (NAC) to treat children with
      ASD and moderate repetitive SIB. NAC is an over-the-counter dietary supplement that may have
      beneficial effects on the brain through its well-documented antioxidant effects and/or
      reduced glutamate signaling. In the proposed study, 14 children with ASD and repetitive SIB
      between the ages of 5 and 12 will be randomly assigned to gradually increasing doses of NAC
      or placebo for 9 weeks. The research team, parents and children will be blind to the
      treatment with NAC or placebo. Participants will come to the research site periodically to
      complete measures and behavioral assessments.

      After the 9 weeks of treatment, children randomized to NAC who showed improvement will be
      encouraged to continue taking the supplement outside the study. Children who were randomly
      assigned to the placebo and showed no improvement will be offered open-label treatment with
      NAC. Children who did not improve while taking NAC or those who improved while on the placebo
      will be advised on next steps by the study team.

      The goal of this feasibility study is establish the acceptability viability of study
      procedures in this vulnerable population, to learn about the potential benefits and adverse
      effects of NAC. Demonstrating these feasibility aims and the preliminary efficacy and safety
      of NAC is a prerequisite for planning a larger, more definitive, study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Percentage of Participants Randomized
time frame: 12 months (throughout the duration of the study)
description: Goal: randomize 1.75 participants per month
measure: Attrition Rate
time frame: 12 months (throughout the duration of the study)
description: Attrition rate is defined as the percent of subjects who did not complete the study. Goal:less than 15% (to indicate that study was acceptable to participants and parents).
measure: Study Medication Compliance
time frame: 12 months (throughout the duration of the study)
description: Goal: at least 70% treatment compliance (tablet counts and drug dairies).
measure: Successful Collection of Outcome Measures
time frame: 12 months (throughout the duration of the study)
description: Goal: at least 80% collection of essential outcome data to demonstrate the feasibility of data collection procedures.
measure: Parent Satisfaction Rating
time frame: Week 9 (at the end of the study intervention)
description: Goal: at least 80% of parents will agree or strongly agree when asked in an anonymous survey that they would recommend the study and the study treatment to other parents of children with ASD and SIB.
measure: Positive Predictive Value of Screening Method of Classifying Self-injurious Behavior (SIB) by Type.
time frame: 12 months (duration of the study)
description: Goal: at least 75% positive predictive value of our screening method to classify children with automatically maintained self-injurious behavior using a semi-structured interview at screening compared to the findings of five- to six-hour functional analysis at baseline. Only children who appear to have automatically maintained SIB will be referred for the baseline evaluation.
Demonstrating a high positive predictive value for the screening method is a necessary prerequisite for launching a larger study. Using the formula: Positive Predictive Value (PPV) = screen positive and true cases ÷ all positive screens, a value of 75% or greater would indicate success of the screening method used.
measure: Aberrant Behavior Checklist Irritability Subscale Score at Baseline and 9 Weeks Post-intervention
time frame: Baseline, Week 9
description: The Aberrant Behavior Checklist (ABC) is a commonly used 58-item parent-rated measure of overall behavioral problems. The Irritability subscale is comprised of 15 items reflecting tantrums, aggression and self injury. Range is 0 to 45, higher scores indicate higher severity. As a preliminary efficacy outcome, it was calculated the average score at baseline and Week 9 post-intervention.
measure: Number of Self-Injurious Behavior Events
time frame: Baseline, Week 9
description: Direct observation of the frequency of SIB was collected at baseline in a separate observational session after completing the functional analysis and again at Week 9. Investigators set a benchmark of an average decline in the frequency of SIB of 50% within the NAC group.
measure: Change in Clinical Global Impression (CGI-I) Scale at 9 Weeks Post-intervention
time frame: Week 9
description: The Clinical Global Impression (CGI-I) scale is a 7-item scale from 1 (Very Much Improved) through 4 (No Change) to 7 (Very Much Worse). By convention, scores of 2 (Much Improved) or 1 (Very Much Improved) are used to define positive response.
measure: Change in Biomarkers and Possible Mechanisms of Action of NAC in Children With ASD.
time frame: Baseline, Week 9
description: Changes amino acid levels before and after NAC treatment: cysteine/cystine and glutathione/glutathione disulfide (GSH/GSSG) ratios (antioxidant effects), glutamate and glutamate/glutamine ratio (glutamate signaling) and GABA levels.
arm group label: Participants taking NAC
arm group type: Experimental
description: Participants randomized to the active treatment study arm will receive gradually increasing doses of N-acetylcysteine (NAC) given as a dissolving tablet in juice or water. NAC is an over-the-counter oral dietary supplement that will be used a higher than usual doses in this study.
arm group label: Participants taking Placebo
arm group type: Placebo Comparator
description: Participants randomized to placebo will receive dissolving tablets identical in size and appearance to the active treatment. Placebo capsules contain inactive ingredients.
intervention type: Drug
intervention name: N-acetylcysteine
description: Participants will start with taking 900mg of NAC once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects will return to the study site to review adverse events.
In the absence of dose limiting adverse events attributable to the study drug, the dose will be gradually increased to 900 mg twice per day for study days 8-28.
If this dose is well-tolerated, the dose will be increased to 900 three times per day for study days 29-63.
arm group label: Participants taking NAC
other name: NAC
intervention type: Drug
intervention name: Placebo
description: Participants will start with taking 900mg of the placebo once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects will return to the study site to review adverse events. The dosing for the placebo will increase in the same fashion as the active treatment.
In the absence of dose limiting adverse events attributable to the study drug, the dose will be gradually increased to 900 mg twice per day for study days 8-28.
If this dose is well-tolerated, the dose will be increased to 900 three times per day for study days 29-63.
arm group label: Participants taking Placebo
criteria: 
gender: All
minimum age: 5 Years
maximum age: 12 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Lawrence Scahill, MSN, PhD
role: Principal Investigator
affiliation: Emory University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Emory University
investigator full name: Lawrence Scahill, MSN, PhD
investigator title: Professor
mesh term: Autistic Disorder
mesh term: Autism Spectrum Disorder
mesh term: Child Development Disorders, Pervasive
mesh term: Self-Injurious Behavior
mesh term: Acetylcysteine
mesh term: N-monoacetylcystine
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 