<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/NCT03757585</url>
  </required_header>
  <id_info>
    <org_study_id>2018P002261</org_study_id>
    <nct_id>NCT03757585</nct_id>
  </id_info>
  <brief_title>Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)</brief_title>
  <official_title>An Open-Label Clinical Trial Conducted Via Telepsychiatry of Complementary and Alternative Treatments (Omega-3 Fatty Acids and Inositol vs. N-acetylcysteine) for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Demarest Lloyd Jr. Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Massachusetts General Hospital</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>
      This study consists of a 6-week, open-label, randomized clinical trial study to compare&#xD;
      efficacy and tolerability of the natural treatments omega-3 fatty acids, inositol, and&#xD;
      N-acetylcysteine (NAC) in the treatment of mood dysregulation in children and adolescents&#xD;
      with non-verbal learning disability (NVLD) or Autism Spectrum Disorder (ASD). Subjects will&#xD;
      include youth ages 5-17 years with a non-verbal learning disability (NVLD) or autism spectrum&#xD;
      disorder (ASD) and current symptoms of emotional dysregulation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 20, 2019</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
  <phase>Phase 4</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean Change in the Parent-Young Mania Rating Scale (P-YMRS) Score</measure>
    <time_frame>Baseline to 6 Weeks</time_frame>
    <description>The YMRS consists of 11 items rated on a scale from 0 (symptoms not present) to 4 (symptoms extremely severe). It is used to assess manic symptoms. The YMRS score ranges from 0-60. Questions are asked about the last week. This scale is generally accepted as the main outcome measure in studies of pediatric bipolar disorder and is linked directly to the core symptoms of mania.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean Change in the Parent-completed Children's Depression Inventory (CDI)</measure>
    <time_frame>Baseline to 6 Weeks</time_frame>
    <description>The CDI consists of 27 items quantifying symptoms such as depressed mood, hedonic capacity, vegetative functions, self-evaluation, and interpersonal behaviors. Each item consists of three statements graded in order of increasing severity from 0 to 2; parents select the one that characterized their child's symptoms best during the past 1 week. The item scores are combined into a total depression score, which ranges from 0 to 54. A higher CDI score means a higher depressive state.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change in the NIMH Clinical Global Improvement scale (CGI)</measure>
    <time_frame>Baseline to 6 Weeks</time_frame>
    <description>The CGI is a measure of illness severity adapted for specific disorders. It allows rating of mania, depression and overall bipolar disorder illness, as well as other conditions frequently comorbid with bipolar disorder. The severity score ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). The improvement score ranges from 1 (very much improved) to 7 (very much worse).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Non-verbal Learning Disorder</condition>
  <condition>Autism Spectrum Disorder</condition>
  <condition>Autism</condition>
  <arm_group>
    <arm_group_label>Omega-3 Fatty Acids + Inositol</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will be treated with 1020mg QAM + 1020mg QPM of omega-3 fatty acids and inositol based on weight (subjects under 25kg: 1000mg QD; Subjects weighing 25kg or more: 2000mg QD).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>N-acetylcysteine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will be treated with N-acetylcysteine capsules (subjects ages 5-12: 1800mg QD; subjects ages 13-17: 2400 mg QD) or effervescent tablets (subjects ages 5-12: 1800mg QD; subjects ages 13-17: 2700 mg QD) based on age.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Open-label Treatment with Omega-3 Fatty Acids + Inositol</intervention_name>
    <description>Open-label Treatment with Omega-3 Fatty Acids + Inositol</description>
    <arm_group_label>Omega-3 Fatty Acids + Inositol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Open-label Treatment with N-acetylcysteine</intervention_name>
    <description>Open-label Treatment with acetylcysteine</description>
    <arm_group_label>N-acetylcysteine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  A previous established diagnosis of non-verbal learning disability (NVLD) or DSM-V&#xD;
             Autism Spectrum Disorder and/ or combined T-scores on the Child Behavior Checklist &gt;&#xD;
             195 on the Withdrawn + Social Problems + Thought Problems subscales.&#xD;
&#xD;
          -  Current symptoms of emotional dysregulation as indicated by combined T-scores on the&#xD;
             Child Behavior Checklist &gt; 180 on the Anxiety/Depression + Aggression + Attention&#xD;
             subscales.&#xD;
&#xD;
          -  Subjects and their caregivers must be English-speaking and have a level of&#xD;
             understanding sufficient to communicate intelligently with the investigator and study&#xD;
             coordinator, and to cooperate with all tests and examinations required by the&#xD;
             protocol.&#xD;
&#xD;
          -  Subjects and their caregivers must be willing and able to comply with all study&#xD;
             procedures.&#xD;
&#xD;
          -  Each subject and his/her authorized legal representative must understand the nature of&#xD;
             the study. The subject's authorized legal representative must sign an informed consent&#xD;
             document and the subject must sign an informed assent document.&#xD;
&#xD;
          -  Subject must be able to swallow pills.&#xD;
&#xD;
          -  Subject must have access to a computer with a camera, speaker, microphone, and&#xD;
             internet connection.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Investigator and his/her immediate family; defined as the investigator's spouse,&#xD;
             parent, child, grandparent, or grandchild.&#xD;
&#xD;
          -  Serious or unstable illness including hepatic, renal, gastroenterological,&#xD;
             respiratory, cardiovascular (including ischemic heart disease), endocrinologic,&#xD;
             neurologic, immunologic, or hematologic disease.&#xD;
&#xD;
          -  History of bleeding diathesis, including those with von Willebrand disease.&#xD;
&#xD;
          -  Uncorrected hypothyroidism or hyperthyroidism.&#xD;
&#xD;
          -  History of sensitivity to omega-3 fatty acids, inositol or NAC. A non-responder or&#xD;
             history of intolerance to omega-3 fatty acid, inositol or NAC after 2 months of&#xD;
             treatment at adequate doses as determined by the clinician.&#xD;
&#xD;
          -  Severe allergies or multiple adverse drug reactions.&#xD;
&#xD;
          -  Unstable or untreated seizure disorder.&#xD;
&#xD;
          -  DSM-IV substance use, abuse or dependence.&#xD;
&#xD;
          -  Judged clinically to be at serious suicidal risk for C-SSRS score ≥ 4.&#xD;
&#xD;
          -  Current diagnosis of schizophrenia.&#xD;
&#xD;
          -  Current diagnosis or symptoms of psychosis.&#xD;
&#xD;
          -  IQ &lt; 70.&#xD;
&#xD;
          -  Pregnant or nursing.&#xD;
&#xD;
          -  Weighs less than 12.5kg.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>5 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Janet Wozniak, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts General Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Hannah O'Connor, BS</last_name>
    <phone>617-643-6617</phone>
    <email>hgoconnor@mgh.harvard.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Abigail Farrell, BS</last_name>
      <phone>617-643-6617</phone>
      <email>aefarrell@partners.org</email>
    </contact>
    <contact_backup>
      <last_name>Haley Driscoll, BA</last_name>
      <phone>617-724-2551</phone>
      <email>hdriscoll2@mgh.harvard.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Janet Wozniak, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>November 27, 2018</study_first_submitted>
  <study_first_submitted_qc>November 27, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 29, 2018</study_first_posted>
  <last_update_submitted>November 1, 2022</last_update_submitted>
  <last_update_submitted_qc>November 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 3, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Janet Wozniak, MD</investigator_full_name>
    <investigator_title>Assistant Professor of Psychiatry</investigator_title>
  </responsible_party>
  <keyword>autism</keyword>
  <keyword>learning disorder</keyword>
  <keyword>natural supplements</keyword>
  <keyword>NAC</keyword>
  <keyword>omega-3</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Learning Disabilities</mesh_term>
    <mesh_term>Autistic Disorder</mesh_term>
    <mesh_term>Autism Spectrum Disorder</mesh_term>
    <mesh_term>Child Development Disorders, Pervasive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Inositol</mesh_term>
    <mesh_term>Acetylcysteine</mesh_term>
    <mesh_term>N-monoacetylcystine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03757585
org study id: 2018P002261
nct id: NCT03757585
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study consists of a 6-week, open-label, randomized clinical trial study to compare
      efficacy and tolerability of the natural treatments omega-3 fatty acids, inositol, and
      N-acetylcysteine (NAC) in the treatment of mood dysregulation in children and adolescents
      with non-verbal learning disability (NVLD) or Autism Spectrum Disorder (ASD). Subjects will
      include youth ages 5-17 years with a non-verbal learning disability (NVLD) or autism spectrum
      disorder (ASD) and current symptoms of emotional dysregulation.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Mean Change in the Parent-Young Mania Rating Scale (P-YMRS) Score
time frame: Baseline to 6 Weeks
description: The YMRS consists of 11 items rated on a scale from 0 (symptoms not present) to 4 (symptoms extremely severe). It is used to assess manic symptoms. The YMRS score ranges from 0-60. Questions are asked about the last week. This scale is generally accepted as the main outcome measure in studies of pediatric bipolar disorder and is linked directly to the core symptoms of mania.
measure: Mean Change in the Parent-completed Children's Depression Inventory (CDI)
time frame: Baseline to 6 Weeks
description: The CDI consists of 27 items quantifying symptoms such as depressed mood, hedonic capacity, vegetative functions, self-evaluation, and interpersonal behaviors. Each item consists of three statements graded in order of increasing severity from 0 to 2; parents select the one that characterized their child's symptoms best during the past 1 week. The item scores are combined into a total depression score, which ranges from 0 to 54. A higher CDI score means a higher depressive state.
measure: Mean Change in the NIMH Clinical Global Improvement scale (CGI)
time frame: Baseline to 6 Weeks
description: The CGI is a measure of illness severity adapted for specific disorders. It allows rating of mania, depression and overall bipolar disorder illness, as well as other conditions frequently comorbid with bipolar disorder. The severity score ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). The improvement score ranges from 1 (very much improved) to 7 (very much worse).
arm group label: Omega-3 Fatty Acids + Inositol
arm group type: Experimental
description: Subjects will be treated with 1020mg QAM + 1020mg QPM of omega-3 fatty acids and inositol based on weight (subjects under 25kg: 1000mg QD; Subjects weighing 25kg or more: 2000mg QD).
arm group label: N-acetylcysteine
arm group type: Experimental
description: Subjects will be treated with N-acetylcysteine capsules (subjects ages 5-12: 1800mg QD; subjects ages 13-17: 2400 mg QD) or effervescent tablets (subjects ages 5-12: 1800mg QD; subjects ages 13-17: 2700 mg QD) based on age.
intervention type: Drug
intervention name: Open-label Treatment with Omega-3 Fatty Acids + Inositol
description: Open-label Treatment with Omega-3 Fatty Acids + Inositol
arm group label: Omega-3 Fatty Acids + Inositol
intervention type: Drug
intervention name: Open-label Treatment with N-acetylcysteine
description: Open-label Treatment with acetylcysteine
arm group label: N-acetylcysteine
criteria: 
gender: All
minimum age: 5 Years
maximum age: 17 Years
healthy volunteers: No
last name: Janet Wozniak, MD
role: Principal Investigator
affiliation: Massachusetts General Hospital
last name: Hannah O'Connor, BS
phone: 617-643-6617
email: hgoconnor@mgh.harvard.edu
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Janet Wozniak, MD
investigator title: Assistant Professor of Psychiatry
mesh term: Learning Disabilities
mesh term: Autistic Disorder
mesh term: Autism Spectrum Disorder
mesh term: Child Development Disorders, Pervasive
mesh term: Inositol
mesh term: Acetylcysteine
mesh term: N-monoacetylcystine
sharing ipd: No