<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/NCT03835117</url>
  </required_header>
  <id_info>
    <org_study_id>MITO</org_study_id>
    <nct_id>NCT03835117</nct_id>
  </id_info>
  <brief_title>Effect of a Wide Spectrum Nutritional Supplement on Mitochondrial Function in Children With Autism Spectrum Disorder</brief_title>
  <official_title>Effect of a Wide Spectrum Nutritional Supplement on Mitochondrial Function in Children With Autism Spectrum Disorder (ASD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rossignol Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Southwest Autism Research &amp; Resource Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Rossignol Medical Center</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 objective of this study is to evaluate the metabolic effects of a comprehensive&#xD;
      wide-spectrum supplement for children with ASD to determine whether it physiologically&#xD;
      targets mitochondrial pathways known to be abnormal in children with ASD.The intervention is&#xD;
      a commonly used wide-spectrum nutritional supplement, which is theoretically designed to&#xD;
      normalize mitochondrial function. The investigators aim to determine if the supplement does&#xD;
      have the hypothesized effect on physiology in individuals with ASD. The investigator will&#xD;
      enroll up to 50 children, aged 4 to 14 years of age with confirmed ASD and mitochondrial&#xD;
      dysfunction, and participation will last 26 weeks.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder often with&#xD;
      life-long consequences that affects young children during critical developmental periods. The&#xD;
      Centers for Disease Control estimates that ASD affects as many as 17 per 1000 children (1 in&#xD;
      59) in the United States suggesting that the prevalence is higher than previous&#xD;
      estimates.Despite the dramatic rise in the detected prevalence of ASD over the past two&#xD;
      decades, there is no effective medical treatment for core ASD symptoms (social communication&#xD;
      and repetitive behavior), the closely associated problem of language impairment, or the&#xD;
      underlying pathophysiology of ASD. Currently, the only accepted treatment for core ASD&#xD;
      symptoms is behavior therapy, which may entail intensive one-on-one treatment over several&#xD;
      years.&#xD;
&#xD;
      The primary aims of this study are to evaluate the effect of a wide-spectrum nutritional&#xD;
      supplement on mitochondrial function in individuals with ASD. Participants entered into the&#xD;
      trial will have abnormalities in mitochondrial function that are known to be associated with&#xD;
      ASD (approximately 50+% of children with ASD) but are not diagnostic of mitochondrial&#xD;
      disease. The investigators hypothesize that nutritional supplements designed for children&#xD;
      with ASD have a physiological action of normalizing mitochondrial function and cellular&#xD;
      physiology throughout the body.&#xD;
&#xD;
      To test whether the targeted nutritional supplement is superior to placebo, the investigators&#xD;
      will study 50 children, between the ages of 4 years to 14 years, with confirmed ASD and known&#xD;
      abnormal variations in mitochondrial at baseline. Participants will be randomly assigned to&#xD;
      receive active treatment or placebo for 12-weeks under double-blind conditions and at the end&#xD;
      of the 12 weeks switch to the opposite condition after a 2-week wash out period.&#xD;
      Mitochondrial function will be measured at baseline and after each treatment arm in order to&#xD;
      determine if the supplement positively influences cellular biochemistry. The investigator&#xD;
      will also evaluate the effectiveness of the supplement on core and associated ASD symptoms&#xD;
      using several behaviors assessments.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">February 1, 2020</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2023</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>Crossover Assignment</intervention_model>
    <intervention_model_description>Prospective Randomized 12-week Double-Blind Placebo-Controlled Cross-over</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in mitochondrial activity in study patients</measure>
    <time_frame>Baseline, Week 12, Week 24</time_frame>
    <description>Mitochondrial activity and redox metabolism at baseline and after the placebo and supplement arms of the study, as determined through laboratory assessment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in the Childhood Autism Rating Scale (CARS) score</measure>
    <time_frame>Baseline, Week 12, Week 24</time_frame>
    <description>The Childhood Autism Rating Scale is a 15-item clinician-rated scale that measures the severity of core ASD symptoms of social communication and restricted and repetitive patterns of behavior, interests, or activities. Each item is scored on a 4 point scale of severity from 1 (None/Minimal) to 4 (Severe). The measure is the total score of the 15 items in which a score of 15-27.5 reflects minimal to no severity of symptoms, 28-33.5 reflects mild to moderate severity of symptoms, and a score of 34 or higher reflects severe symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the Clinical Global Impression scale (CGI) score</measure>
    <time_frame>Baseline, Week 12, Week 24</time_frame>
    <description>The Clinical Global Impression - Severity scale (CGI-S) is a clinician rated 7-point measure of overall symptomatic severity of psychopathology. Scores range from 1 (Normal, not at all ill) through 4 (Moderately ill) to 7 (Among the most extremely ill patients). The Clinical Global Impression - Improvement scale (CGI-I) is the companion measure that evaluates the change in the patient's symptoms relative to baseline. Scores range from 1 (Very much improved) through 4 (No Change) to 7 (Very much worse). Ratings are reflected in a single total score, in which a score of 2 (Much Improved) or 1 (Very Much Improved) on the CGI-I will be used as a secondary measure to define positive response.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the Children's Yale-Brown Obsessive Compulsive Scale modified for Autism Spectrum Disorder (CYBOCS-ASD) score</measure>
    <time_frame>Baseline, Week 12, Week 24</time_frame>
    <description>The Children's Yale-Brown Obsessive Compulsive Scale modified for Autism Spectrum Disorder is a 5-item clinician-rated measure to evaluate severity of repetitive behavior in children with ASD. Each item is scored on a 5 point scale from 0 (None) to 4 (Extreme) for the severity of: Time Spent, Interference in everyday life, Distress, Resistance, and Degree of Control over the behavior. A decrease in the total score of the 5 items, ranging from 0 to 20, will be used as a secondary measure to define positive response.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the Aberrant Behavior Checklist (ABC) scores</measure>
    <time_frame>Screening, Week 12, Week 24</time_frame>
    <description>The Aberrant Behavior Checklist is a 58-item caregiver questionnaire consisting of five subscales: hyperactivity, irritability, social withdrawal, stereotypic behavior and inappropriate speech in children with developmental disabilities. A higher score indicates more frequent aberrant behaviors. Our secondary measures are the subscale scores for Irritability (15 item), Social Withdrawal (16 item) and Hyperactivity (16 item). Each item rates behavior severity on a 4 point scale from 0 (Not at all a problem) to 3 (The problem is severe in degree). A decrease in the subscale scores, ranging from 0 to 45 (Irritability), 48 (Social Withdrawal) and 48 (Hyperactivity), will be used as secondary measures to define positive response.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the Parent-rated Anxiety Scale for ASD (PRAS-ASD) score</measure>
    <time_frame>Baseline, Week 12, Week 24</time_frame>
    <description>The Parent-rated Anxiety Scale for Autism Spectrum Disorder is a 25-item scale that measures anxiety in youth with ASD. Each item rates the severity of a behavior on a 4 point scale from 0 (None/not present) to 3 (Severe/Very frequent and a major problem). A decrease in the total score of the 25 items, ranging from 0 to 75, will be used as a secondary measure to define positive response to intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the Caregiver Strain Questionnaire (CGSQ) score</measure>
    <time_frame>Baseline, Week 12, Week 24</time_frame>
    <description>The Caregiver Strain short-form questionnaire is a 7-item measure of self-reported strain experienced by caregivers of children with behavioral disorders. Each item rates the severity of interference in the quality of the caregiver's life on a 5 point scale from 0 (Not at All) to 4 (Very Much). A decrease in the total score of the 7 items, ranging from 0 to 28, will be used as a secondary measure to define positive response.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the Vineland III Caregiver score</measure>
    <time_frame>Baseline, Week 12, Week 24</time_frame>
    <description>The Vineland III Caregiver is a 381-item parent-reported measure of adaptive behavior in children with developmental and intellectual disabilities. The Vineland is comprised of three sub scores for the following domains: Communication, Daily Living Skills, and Socialization. The frequency of adaptive behaviors for each item is scored on a scale from 0 (Never) to 2 (Usually). The total adaptive score is reflected as a composite score of the sub domains (which is determined by age norms) in which a higher total score reflects higher functioning. An increase in the total score or sub domain scores will be used as a secondary measure to define positive response to intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate intervention safety</measure>
    <time_frame>Screening, Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24</time_frame>
    <description>Columbia-Suicide Severity Rating Scale: a suicide risk assessment that identifies presence and severity of suicidal ideation, planning, and behavior, as well as non-suicidal self-harm behaviors. Presence of any of these behaviors during the course of study enrollment will be considered an adverse event.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate intervention safety</measure>
    <time_frame>Screening, Week 12, Week 24</time_frame>
    <description>Routine complete blood counts will be collected to determine whether treatment-emergent basic blood chemistry is altered. Presence of any changes during the course of study enrollment will be evaluated by the treating physician and determined clinically significant or not clinically significant. If determined by the treating physician, a change will be considered an adverse event.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate intervention safety</measure>
    <time_frame>Screening, Week 12, Week 24</time_frame>
    <description>Routine comprehensive blood panels will be collected to determine whether treatment-emergent basic blood chemistry is altered. Presence of any changes during the course of study enrollment will be evaluated by the treating physician and determined clinically significant or not clinically significant. If determined by the treating physician, a change will be considered an adverse event.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate intervention effect on cellular regulatory pathways known to be implicated in ASD</measure>
    <time_frame>Screening, Week 12, Week 24</time_frame>
    <description>Evaluation of a variety of research biomarkers, including peripheral blood mononuclear cell, plasma, DNA, red blood cells, and oxidative stress rates. Treatment-emergent change in these biomarkers will indicate that a change has occurred at the cellular level.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Examine the change in attention to social stimuli</measure>
    <time_frame>Baseline, Week 12, Week 24</time_frame>
    <description>Participants will watch a video with social and non-social stimuli. Eye movements and visual fixation will be measured with eye tracking software. Change in percentage of time spent looking at social stimuli will be measured.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Examine the change in cognitive ability</measure>
    <time_frame>Screening, Week 12, Week 24</time_frame>
    <description>Differential Abilities Scale-II: cognitive abilities across core domains: verbal, nonverbal, spatial. Subtests: Verbal comprehension: 42-item domain, raw score 0-23. Naming vocabulary: 34-item domain, raw score 0-28. Word definitions: 35-item domain, raw score 0-25. Verbal similarities: 33-item domain, raw score 0-28. Picture similarities: 32-item domain, raw score 0-23. Picture similarities: 50-item domain, raw score 0-34. Matrices: 56-item domain, raw score 0-33. Pattern construction: 35-item domain, raw score 0-74. Copying: 20-item domain, raw score 0-36. Recall of designs: 22-item domain, raw score 0-43. All subdomains have a t-score range of 10-90. Verbal ability standard score ranges from 30-170. Nonverbal ability standard score ranges from 32-170. Spatial ability standard score ranges from 34-170. Total General Conceptual Ability standard score ranges from 30-170. Subtests and item sets given vary by participant age</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Autism Spectrum Disorder</condition>
  <arm_group>
    <arm_group_label>Wide-spectrum nutritional supplement</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The Wide-spectrum nutritional supplement used will be a combination of NeuroNeeds: SpectrumNeeds and QNeeds. Weight based dosing will be used. The daily serving size will be divided into two oral daily doses in the form of a powder which can be mixed into liquid or food. Together, there are 34 different dietary supplements in the products. Except for ubiquinol, all of these nutrients are provided in a powder form in SpectrumNeeds. Ubiquinol is provided separately in QNeeds gel capsules. These capsules can be swallowed whole, or cut with scissors and the contents squeezed out and added to SpectrumNeeds just before ingestion.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants randomized to receive placebo will take placebo in an oral form divided into powder and a gel capsule in the same manner as treatment. For the second phase of the cross over, participants will be part of the opposite group they were assigned to in Phase I (Placebo or Treatment). Quantities for placebo or treatment will match across phases for each subject, utilizing the same weight based dosing.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Wide-spectrum nutritional supplement</intervention_name>
    <description>Comprehensive powder with 33 dietary supplements and 1 dietary supplement via gel capsule.</description>
    <arm_group_label>Wide-spectrum nutritional supplement</arm_group_label>
    <other_name>NeuroNeeds: Spectrum Needs, NeuroNeeds:Q Needs</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Inactive placebo comparator</description>
    <arm_group_label>Placebo control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Weight ≥ 15 kg and ≤ 100kg;&#xD;
&#xD;
          -  DSM-5 diagnosis of Autism Spectrum Disorder as established by formal clinical&#xD;
             assessment which includes a gold-standard tool such as the Autism Diagnostic&#xD;
             Observational Schedule.&#xD;
&#xD;
          -  Current Clinical Global Impression Severity score ≥ 4&#xD;
&#xD;
          -  Stable educational and therapy plan (one month) with no planned changes in the&#xD;
             intensity of treatment for 12 weeks.&#xD;
&#xD;
          -  English is spoken in the home and at least one parent is able to read, write and speak&#xD;
             English.&#xD;
&#xD;
          -  Stable medication (no changes in past 6 weeks and no planned changes for the study&#xD;
             duration.&#xD;
&#xD;
          -  Electron Transport Chain Complex (I, II, III, IV) or Citrate Synthase Activity which&#xD;
             is &gt;= 2.0 Standard Deviation Above or Below Average (outside the normal range)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Presence of serious behavioral problems (tantrums, aggression, self-injury) for which&#xD;
             another treatment is warranted.&#xD;
&#xD;
          -  Current Clinical Global Impression Severity score &lt; 7 (Extremely Ill)&#xD;
&#xD;
          -  Significant medical condition by history or by physical examination or lab tests that&#xD;
             would be incompatible with the treatment.&#xD;
&#xD;
          -  Children taking anticonvulsant medication for seizures or active epilepsy.&#xD;
&#xD;
          -  Diagnosis of Mitochondrial Disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Richard E Frye, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rossignol Medical Center, Phoenix AZ</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Southwestern Research &amp; Resource Center</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Delhey LM, Nur Kilinc E, Yin L, Slattery JC, Tippett ML, Rose S, Bennuri SC, Kahler SG, Damle S, Legido A, Goldenthal MJ, Frye RE. The Effect of Mitochondrial Supplements on Mitochondrial Activity in Children with Autism Spectrum Disorder. J Clin Med. 2017 Feb 13;6(2):18. doi: 10.3390/jcm6020018.</citation>
    <PMID>28208802</PMID>
  </reference>
  <reference>
    <citation>Rose S, Niyazov DM, Rossignol DA, Goldenthal M, Kahler SG, Frye RE. Clinical and Molecular Characteristics of Mitochondrial Dysfunction in Autism Spectrum Disorder. Mol Diagn Ther. 2018 Oct;22(5):571-593. doi: 10.1007/s40291-018-0352-x.</citation>
    <PMID>30039193</PMID>
  </reference>
  <reference>
    <citation>Frye RE, Rossignol DA. Treatments for biomedical abnormalities associated with autism spectrum disorder. Front Pediatr. 2014 Jun 27;2:66. doi: 10.3389/fped.2014.00066. eCollection 2014.</citation>
    <PMID>25019065</PMID>
  </reference>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>February 5, 2019</study_first_submitted>
  <study_first_submitted_qc>February 6, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 8, 2019</study_first_posted>
  <last_update_submitted>September 26, 2022</last_update_submitted>
  <last_update_submitted_qc>September 26, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 28, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Rossignol Medical Center</investigator_affiliation>
    <investigator_full_name>Richard Eugene Frye</investigator_full_name>
    <investigator_title>Director of Research</investigator_title>
  </responsible_party>
  <keyword>Mitochondrial Dysfunction</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>
  </condition_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/NCT03835117
org study id: MITO
nct id: NCT03835117
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The objective of this study is to evaluate the metabolic effects of a comprehensive
      wide-spectrum supplement for children with ASD to determine whether it physiologically
      targets mitochondrial pathways known to be abnormal in children with ASD.The intervention is
      a commonly used wide-spectrum nutritional supplement, which is theoretically designed to
      normalize mitochondrial function. The investigators aim to determine if the supplement does
      have the hypothesized effect on physiology in individuals with ASD. The investigator will
      enroll up to 50 children, aged 4 to 14 years of age with confirmed ASD and mitochondrial
      dysfunction, and participation will last 26 weeks.
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder often with
      life-long consequences that affects young children during critical developmental periods. The
      Centers for Disease Control estimates that ASD affects as many as 17 per 1000 children (1 in
      59) in the United States suggesting that the prevalence is higher than previous
      estimates.Despite the dramatic rise in the detected prevalence of ASD over the past two
      decades, there is no effective medical treatment for core ASD symptoms (social communication
      and repetitive behavior), the closely associated problem of language impairment, or the
      underlying pathophysiology of ASD. Currently, the only accepted treatment for core ASD
      symptoms is behavior therapy, which may entail intensive one-on-one treatment over several
      years.

      The primary aims of this study are to evaluate the effect of a wide-spectrum nutritional
      supplement on mitochondrial function in individuals with ASD. Participants entered into the
      trial will have abnormalities in mitochondrial function that are known to be associated with
      ASD (approximately 50+% of children with ASD) but are not diagnostic of mitochondrial
      disease. The investigators hypothesize that nutritional supplements designed for children
      with ASD have a physiological action of normalizing mitochondrial function and cellular
      physiology throughout the body.

      To test whether the targeted nutritional supplement is superior to placebo, the investigators
      will study 50 children, between the ages of 4 years to 14 years, with confirmed ASD and known
      abnormal variations in mitochondrial at baseline. Participants will be randomly assigned to
      receive active treatment or placebo for 12-weeks under double-blind conditions and at the end
      of the 12 weeks switch to the opposite condition after a 2-week wash out period.
      Mitochondrial function will be measured at baseline and after each treatment arm in order to
      determine if the supplement positively influences cellular biochemistry. The investigator
      will also evaluate the effectiveness of the supplement on core and associated ASD symptoms
      using several behaviors assessments.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Prospective Randomized 12-week Double-Blind Placebo-Controlled Cross-over
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in mitochondrial activity in study patients
time frame: Baseline, Week 12, Week 24
description: Mitochondrial activity and redox metabolism at baseline and after the placebo and supplement arms of the study, as determined through laboratory assessment.
measure: Change in the Childhood Autism Rating Scale (CARS) score
time frame: Baseline, Week 12, Week 24
description: The Childhood Autism Rating Scale is a 15-item clinician-rated scale that measures the severity of core ASD symptoms of social communication and restricted and repetitive patterns of behavior, interests, or activities. Each item is scored on a 4 point scale of severity from 1 (None/Minimal) to 4 (Severe). The measure is the total score of the 15 items in which a score of 15-27.5 reflects minimal to no severity of symptoms, 28-33.5 reflects mild to moderate severity of symptoms, and a score of 34 or higher reflects severe symptoms.
measure: Change in the Clinical Global Impression scale (CGI) score
time frame: Baseline, Week 12, Week 24
description: The Clinical Global Impression - Severity scale (CGI-S) is a clinician rated 7-point measure of overall symptomatic severity of psychopathology. Scores range from 1 (Normal, not at all ill) through 4 (Moderately ill) to 7 (Among the most extremely ill patients). The Clinical Global Impression - Improvement scale (CGI-I) is the companion measure that evaluates the change in the patient's symptoms relative to baseline. Scores range from 1 (Very much improved) through 4 (No Change) to 7 (Very much worse). Ratings are reflected in a single total score, in which a score of 2 (Much Improved) or 1 (Very Much Improved) on the CGI-I will be used as a secondary measure to define positive response.
measure: Change in the Children's Yale-Brown Obsessive Compulsive Scale modified for Autism Spectrum Disorder (CYBOCS-ASD) score
time frame: Baseline, Week 12, Week 24
description: The Children's Yale-Brown Obsessive Compulsive Scale modified for Autism Spectrum Disorder is a 5-item clinician-rated measure to evaluate severity of repetitive behavior in children with ASD. Each item is scored on a 5 point scale from 0 (None) to 4 (Extreme) for the severity of: Time Spent, Interference in everyday life, Distress, Resistance, and Degree of Control over the behavior. A decrease in the total score of the 5 items, ranging from 0 to 20, will be used as a secondary measure to define positive response.
measure: Change in the Aberrant Behavior Checklist (ABC) scores
time frame: Screening, Week 12, Week 24
description: The Aberrant Behavior Checklist is a 58-item caregiver questionnaire consisting of five subscales: hyperactivity, irritability, social withdrawal, stereotypic behavior and inappropriate speech in children with developmental disabilities. A higher score indicates more frequent aberrant behaviors. Our secondary measures are the subscale scores for Irritability (15 item), Social Withdrawal (16 item) and Hyperactivity (16 item). Each item rates behavior severity on a 4 point scale from 0 (Not at all a problem) to 3 (The problem is severe in degree). A decrease in the subscale scores, ranging from 0 to 45 (Irritability), 48 (Social Withdrawal) and 48 (Hyperactivity), will be used as secondary measures to define positive response.
measure: Change in the Parent-rated Anxiety Scale for ASD (PRAS-ASD) score
time frame: Baseline, Week 12, Week 24
description: The Parent-rated Anxiety Scale for Autism Spectrum Disorder is a 25-item scale that measures anxiety in youth with ASD. Each item rates the severity of a behavior on a 4 point scale from 0 (None/not present) to 3 (Severe/Very frequent and a major problem). A decrease in the total score of the 25 items, ranging from 0 to 75, will be used as a secondary measure to define positive response to intervention.
measure: Change in the Caregiver Strain Questionnaire (CGSQ) score
time frame: Baseline, Week 12, Week 24
description: The Caregiver Strain short-form questionnaire is a 7-item measure of self-reported strain experienced by caregivers of children with behavioral disorders. Each item rates the severity of interference in the quality of the caregiver's life on a 5 point scale from 0 (Not at All) to 4 (Very Much). A decrease in the total score of the 7 items, ranging from 0 to 28, will be used as a secondary measure to define positive response.
measure: Change in the Vineland III Caregiver score
time frame: Baseline, Week 12, Week 24
description: The Vineland III Caregiver is a 381-item parent-reported measure of adaptive behavior in children with developmental and intellectual disabilities. The Vineland is comprised of three sub scores for the following domains: Communication, Daily Living Skills, and Socialization. The frequency of adaptive behaviors for each item is scored on a scale from 0 (Never) to 2 (Usually). The total adaptive score is reflected as a composite score of the sub domains (which is determined by age norms) in which a higher total score reflects higher functioning. An increase in the total score or sub domain scores will be used as a secondary measure to define positive response to intervention.
measure: Evaluate intervention safety
time frame: Screening, Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24
description: Columbia-Suicide Severity Rating Scale: a suicide risk assessment that identifies presence and severity of suicidal ideation, planning, and behavior, as well as non-suicidal self-harm behaviors. Presence of any of these behaviors during the course of study enrollment will be considered an adverse event.
measure: Evaluate intervention safety
time frame: Screening, Week 12, Week 24
description: Routine complete blood counts will be collected to determine whether treatment-emergent basic blood chemistry is altered. Presence of any changes during the course of study enrollment will be evaluated by the treating physician and determined clinically significant or not clinically significant. If determined by the treating physician, a change will be considered an adverse event.
measure: Evaluate intervention safety
time frame: Screening, Week 12, Week 24
description: Routine comprehensive blood panels will be collected to determine whether treatment-emergent basic blood chemistry is altered. Presence of any changes during the course of study enrollment will be evaluated by the treating physician and determined clinically significant or not clinically significant. If determined by the treating physician, a change will be considered an adverse event.
measure: Evaluate intervention effect on cellular regulatory pathways known to be implicated in ASD
time frame: Screening, Week 12, Week 24
description: Evaluation of a variety of research biomarkers, including peripheral blood mononuclear cell, plasma, DNA, red blood cells, and oxidative stress rates. Treatment-emergent change in these biomarkers will indicate that a change has occurred at the cellular level.
measure: Examine the change in attention to social stimuli
time frame: Baseline, Week 12, Week 24
description: Participants will watch a video with social and non-social stimuli. Eye movements and visual fixation will be measured with eye tracking software. Change in percentage of time spent looking at social stimuli will be measured.
measure: Examine the change in cognitive ability
time frame: Screening, Week 12, Week 24
description: Differential Abilities Scale-II: cognitive abilities across core domains: verbal, nonverbal, spatial. Subtests: Verbal comprehension: 42-item domain, raw score 0-23. Naming vocabulary: 34-item domain, raw score 0-28. Word definitions: 35-item domain, raw score 0-25. Verbal similarities: 33-item domain, raw score 0-28. Picture similarities: 32-item domain, raw score 0-23. Picture similarities: 50-item domain, raw score 0-34. Matrices: 56-item domain, raw score 0-33. Pattern construction: 35-item domain, raw score 0-74. Copying: 20-item domain, raw score 0-36. Recall of designs: 22-item domain, raw score 0-43. All subdomains have a t-score range of 10-90. Verbal ability standard score ranges from 30-170. Nonverbal ability standard score ranges from 32-170. Spatial ability standard score ranges from 34-170. Total General Conceptual Ability standard score ranges from 30-170. Subtests and item sets given vary by participant age
arm group label: Wide-spectrum nutritional supplement
arm group type: Experimental
description: The Wide-spectrum nutritional supplement used will be a combination of NeuroNeeds: SpectrumNeeds and QNeeds. Weight based dosing will be used. The daily serving size will be divided into two oral daily doses in the form of a powder which can be mixed into liquid or food. Together, there are 34 different dietary supplements in the products. Except for ubiquinol, all of these nutrients are provided in a powder form in SpectrumNeeds. Ubiquinol is provided separately in QNeeds gel capsules. These capsules can be swallowed whole, or cut with scissors and the contents squeezed out and added to SpectrumNeeds just before ingestion.
arm group label: Placebo control
arm group type: Placebo Comparator
description: Participants randomized to receive placebo will take placebo in an oral form divided into powder and a gel capsule in the same manner as treatment. For the second phase of the cross over, participants will be part of the opposite group they were assigned to in Phase I (Placebo or Treatment). Quantities for placebo or treatment will match across phases for each subject, utilizing the same weight based dosing.
intervention type: Drug
intervention name: Wide-spectrum nutritional supplement
description: Comprehensive powder with 33 dietary supplements and 1 dietary supplement via gel capsule.
arm group label: Wide-spectrum nutritional supplement
other name: NeuroNeeds: Spectrum Needs, NeuroNeeds:Q Needs
intervention type: Other
intervention name: Placebo
description: Inactive placebo comparator
arm group label: Placebo control
criteria: 
gender: All
minimum age: 2 Years
maximum age: 17 Years
healthy volunteers: No
last name: Richard E Frye, MD, PhD
role: Principal Investigator
affiliation: Rossignol Medical Center, Phoenix AZ
facility: 
country: United States
citation: Delhey LM, Nur Kilinc E, Yin L, Slattery JC, Tippett ML, Rose S, Bennuri SC, Kahler SG, Damle S, Legido A, Goldenthal MJ, Frye RE. The Effect of Mitochondrial Supplements on Mitochondrial Activity in Children with Autism Spectrum Disorder. J Clin Med. 2017 Feb 13;6(2):18. doi: 10.3390/jcm6020018.
PMID: 28208802
citation: Rose S, Niyazov DM, Rossignol DA, Goldenthal M, Kahler SG, Frye RE. Clinical and Molecular Characteristics of Mitochondrial Dysfunction in Autism Spectrum Disorder. Mol Diagn Ther. 2018 Oct;22(5):571-593. doi: 10.1007/s40291-018-0352-x.
PMID: 30039193
citation: Frye RE, Rossignol DA. Treatments for biomedical abnormalities associated with autism spectrum disorder. Front Pediatr. 2014 Jun 27;2:66. doi: 10.3389/fped.2014.00066. eCollection 2014.
PMID: 25019065
responsible party type: Principal Investigator
investigator affiliation: Rossignol Medical Center
investigator full name: Richard Eugene Frye
investigator title: Director of Research
mesh term: Autistic Disorder
mesh term: Autism Spectrum Disorder
mesh term: Child Development Disorders, Pervasive
sharing ipd: No