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Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder

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ClinicalTrials.gov Identifier: NCT02909959
Recruitment Status : Completed
First Posted : September 21, 2016
Last Update Posted : June 25, 2019
Sponsor:
Collaborator:
North Carolina Translational and Clinical Sciences Institute
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill

Tracking Information
First Submitted Date  ICMJE September 7, 2016
First Posted Date  ICMJE September 21, 2016
Last Update Posted Date June 25, 2019
Actual Study Start Date  ICMJE March 1, 2017
Actual Primary Completion Date May 30, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 16, 2016)
Change in Social Responsiveness Scale-2 (SRS-2) total scores from baseline to weeks 4, 8, 12 and 16. [ Time Frame: Baseline, 4 weeks, 8 weeks, 12 weeks, 16 weeks ]
The SRS-2 is a 65-item caregiver report that includes 5 subscales covering core symptom domains of ASD (Social Awareness, Social Cognition, Social Communication, Social Motivation, and Restricted Interests/ Repetitive Behaviors).
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02909959 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 26, 2017)
  • Change in SRS-2 subscale scores (Social Awareness, Social Cognition, Social Communication, Social Motivation, and Restricted Interests/ Repetitive Behaviors) from baseline to weeks 4, 8, 12 and 16. [ Time Frame: Baseline, 4 weeks, 8 weeks, 12 weeks, 16 weeks ]
  • Change in Aberrant Behavior Checklist (ABC) subscale scores (Social Withdrawal, Hyperactivity, Inappropriate Speech, Stereotypy, and Irritability) from baseline to weeks 4, 8, 12, and 16. [ Time Frame: Baseline, 4 weeks, 8 weeks, 12 weeks, 16 weeks ]
    The ABC is a 58-item caregiver questionnaire developed to assess medication effects in individuals with developmental disorders and includes 5 distinct subscales of behavioral symptoms.
  • Change in Clinical Global Impression-Severity (CGI-S) scores from baseline to weeks 4, 8, 12, and 16. [ Time Frame: Baseline, 4 weeks, 8 weeks, 12 weeks, 16 weeks ]
    The CGI-Severity (CGI-S) scale is a 7-point, clinician-rated scale providing an overall assessment of patient functioning relative to other patients with a similar diagnosis (1=not at all ill to 7=severely ill).
  • Differences in Clinical Global Impression- Improvement (CGI-I) scores between treatment arms at weeks 4, 8, 12, and 16. [ Time Frame: 4 weeks, 8 weeks, 12 weeks, 16 weeks ]
    The CGI-Improvement (CGI-I) scale rates overall improvement or worsening of illness (ie, ASD) relative to baseline. The proportion of subjects in each treatment arm with CGI-I scores of 1 ("very much improved") or 2 ("much improved") at weeks 4, 8, 12, and 16 will be calculated and compared for between-group differences.
  • Change in Repetitive Behavior Scale-Revised (RBSR) total scores from baseline to weeks 4, 8, 12, and 16. [ Time Frame: Baseline, 4 weeks, 8 weeks, 12 weeks, 16 weeks ]
    The RBS-R is a 43-item, informant-based questionnaire designed to quantify a range of restricted, repetitive behaviors (RRB) observed in ASD.
  • Complete Blood Count (CBC) with differential, change in values from baseline to 12 weeks [ Time Frame: Baseline, 12 weeks ]
  • Liver function tests (alanine transaminase, aspartate transaminase, total bilirubin), change values from baseline to 12 weeks [ Time Frame: Baseline, 12 weeks ]
  • Serum chemistries (sodium, potassium, chloride, bicarbonate, Blood Urea Nitrogen, creatinine, calcium, magnesium, phosphorous, glucose), change in values from baseline to 12 weeks. [ Time Frame: Baseline and 12 weeks ]
  • Thyroid Stimulating Hormone (TSH), change in values from baseline to 12 weeks. [ Time Frame: Baseline and 12 weeks ]
  • Vital signs (weight, height, blood pressure, and heart rate), actual values at each time point measured and change in values from Baseline to Weeks 4, 8, 12, and 16. [ Time Frame: Baseline, 4 weeks, 8 weeks, 12 weeks, 16 weeks ]
  • Change in the concentration of sulforaphane metabolites (dithiocarbamates) in serum samples from baseline to week 12, the end of the active treatment phase. [ Time Frame: Baseline and 12 weeks ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 16, 2016)
  • Change in SRS-2 subscale scores (Social Awareness, Social Cognition, Social Communication, Social Motivation, and Restricted Interests/ Repetitive Behaviors) from baseline to weeks 4, 8, 12 and 16. [ Time Frame: Baseline, 4 weeks, 8 weeks, 12 weeks, 16 weeks ]
  • Change in Aberrant Behavior Checklist (ABC) subscale scores (Social Withdrawal, Hyperactivity, Inappropriate Speech, Stereotypy, and Irritability) from baseline to weeks 4, 8, 12, and 16. [ Time Frame: Baseline, 4 weeks, 8 weeks, 12 weeks, 16 weeks ]
    The ABC is a 58-item caregiver questionnaire developed to assess medication effects in individuals with developmental disorders and includes 5 distinct subscales of behavioral symptoms.
  • Change in Clinical Global Impression-Severity (CGI-S) scores from baseline to weeks 4, 8, 12, and 16. [ Time Frame: Baseline, 4 weeks, 8 weeks, 12 weeks, 16 weeks ]
    The CGI-Severity (CGI-S) scale is a 7-point, clinician-rated scale providing an overall assessment of patient functioning relative to other patients with a similar diagnosis (1=not at all ill to 7=severely ill).
  • Differences in Clinical Global Impression- Improvement (CGI-I) scores between treatment arms at weeks 4, 8, 12, and 16. [ Time Frame: 4 weeks, 8 weeks, 12 weeks, 16 weeks ]
    The CGI-Improvement (CGI-I) scale rates overall improvement or worsening of illness (ie, ASD) relative to baseline. The proportion of subjects in each treatment arm with CGI-I scores of 1 ("very much improved") or 2 ("much improved") at weeks 4, 8, 12, and 16 will be calculated and compared for between-group differences.
  • Change in Repetitive Behavior Scale-Revised (RBSR) total scores from baseline to weeks 4, 8, 12, and 16. [ Time Frame: Baseline, 4 weeks, 8 weeks, 12 weeks, 16 weeks ]
    The RBS-R is a 43-item, informant-based questionnaire designed to quantify a range of restricted, repetitive behaviors (RRB) observed in ASD.
  • Complete Blood Count (CBC) with differential, change in values from baseline to 12 weeks [ Time Frame: Baseline, 12 weeks ]
  • Liver function tests (alanine transaminase, aspartate transaminase, total bilirubin), change values from baseline to 12 weeks [ Time Frame: Baseline, 12 weeks ]
  • Serum chemistries (sodium, potassium, chloride, bicarbonate, Blood Urea Nitrogen, creatinine, calcium, magnesium, phosphorous, glucose), change in values from baseline to 12 weeks. [ Time Frame: Baseline and 12 weeks ]
  • Thyroid Stimulating Hormone (TSH), change in values from baseline to 12 weeks. [ Time Frame: Baseline and 12 weeks ]
  • Vital signs (weight, height, blood pressure, and heart rate), actual values at each time point measured and change in values from Baseline to Weeks 4, 8, 12, and 16. [ Time Frame: Baseline, 4 weeks, 8 weeks, 12 weeks, 16 weeks ]
  • Change in the concentration of sulforaphane metabolites (dithiocarbamates) in overnight voided urine samples from baseline to week 12, the end of the active treatment phase. [ Time Frame: Baseline and 12 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
Official Title  ICMJE A Phase II, Randomized, Double-blind, Placebo-controlled Study of Myrosinase-enriched Glucoraphanin, a Sulforaphane Precursor System, in Autism Spectrum Disorder
Brief Summary The aim of this randomized controlled trial is to determine if a nutritional supplement containing broccoli sprout and seed extracts, a rich source of sulforaphane, is effective in reducing core symptoms of autism spectrum disorder (ASD). The study will also explore the safety and tolerability of a sulforaphane supplement in young men with ASD, as well as its effects on challenging neuropsychiatric symptoms that are commonly associated with ASD, such as hyperactivity, irritability, and repetitive movements.
Detailed Description

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1 in 68 children, including 1 in 42 boys, characterized by marked social communication impairment and restricted, repetitive behaviors and interests. Evidence-based pharmacological treatments available for the treatment of the defining symptoms of ASD are currently lacking.

While the etiology of ASD is not fully understood, the pathogenesis is hypothesized to involve cellular dysfunction, including increased oxidative stress, aberrant neuroinflammation, and reduced mitochondrial capacity, leading to synaptic dysfunction in at least a subset of individuals. Sulforaphane is a powerful upregulator of antioxidant response elements and heat shock proteins, which may lead to improved redox capacity, decreased inflammation, and improved mitochondrial functioning in individuals with ASD. A trial by Singh and colleagues (2014) provided preliminary evidence suggesting that sulforaphane derived from broccoli sprout extract can have beneficial effects for improving symptoms of autism.

In this study, young men ages 13-30 years old with moderate to severe autism spectrum disorder will be randomly assigned to receive either a sulforaphane supplement or placebo for a 12 week treatment treatment period, followed by a 4 week blinded discontinuation phase. The uncoated tablets each contain 125 mg broccoli seed extract and 50 mg broccoli sprout extract, corresponding to approximately 15 µmol sulforaphane per tablet. The dose will vary from 3-8 tablets daily depending upon the participant's weight. Matched placebo tablets contain only inert ingredients

A serum sample will be collected prior to starting treatment and at the end of the treatment phase to quantify sulforaphane metabolites. Clinical response will be assessed through clinician- and caregiver-rated measures of autism symptoms (Social Responsiveness Scale-2; Repetitive Behavior Scale- Revised), challenging symptoms commonly observed in individuals with developmental disabilities (Aberrant Behavior Checklist), and global severity of symptoms and improvement (Clinical Global Impression Scale). A blood sample will be collected at baseline and at the end of the treatment phase to check safety labs, and a saliva sample will be collected at baseline for a future study of genetic biomarkers associated with treatment response.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Autism Spectrum Disorder
  • Autistic Disorder
  • Neurodevelopmental Disorder
  • Childhood Developmental Disorders, Pervasive
Intervention  ICMJE
  • Drug: Sulforaphane
    The investigational medicinal product is an uncoated tablet containing both glucoraphanin and myrosinase, the enzyme that converts glucoraphanin to sulforaphane in vivo. Participants in this arm will take 3-8 tablets by mouth once daily (dose depending upon weight) for 12 weeks.
    Other Names:
    • Avmacol
    • glucoraphanin
  • Drug: Placebo
    Placebo tablets are uncoated and matched in appearance to the investigational medicinal product, containing inert components. Participants in this arm will take 3-8 tablets by mouth once daily (dose depending upon weight) for 12 weeks.
    Other Name: Control
Study Arms  ICMJE
  • Active Comparator: Sulforaphane

    Participants will take a sulforaphane supplement 3-8 tablets daily, with dose depending upon body weight. Each tablet contains 125 mg broccoli seed powder and 50 mg broccoli sprout extract, providing approximately 15 µmol sulforaphane.

    The weight-based dosing schedule is as follows:

    3 tablets (approx. 46.5 µmol SF) if <100 lb; 5 tablets (approx. 77.5 µmol SF) if 100-125 lb; 6 tablets (approx. 93 µmol SF) if 126-175 lb; 7 tablets (approx. 108.5 µmol SF) if 176-199 lb; 8 tablets (approx. 124 µmol SF) if ≥ 200 lb

    Intervention: Drug: Sulforaphane
  • Placebo Comparator: Placebo
    Participants in this arm will take placebo tablets that are identical in shape, size, and color to the sulforaphane tablets. The number of tablets taken per day corresponds to the weight-based schedule described for the sulforaphane arm.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 21, 2019)
48
Original Estimated Enrollment  ICMJE
 (submitted: September 16, 2016)
54
Actual Study Completion Date  ICMJE May 30, 2019
Actual Primary Completion Date May 30, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Males between ages 13-30 (inclusive) at the time of the consent
  • Primary diagnosis of Autism Spectrum Disorder (ASD), confirmed by Diagnostic and Statistical Manual-5 (DSM-5) criteria and meeting the autism cut-off score of 9 or greater on the Autism Diagnostic Observation Schedule-2 (ADOS-2)
  • Participant is capable of giving written informed consent or has a legally authorized representative (LAR) with sufficient capacity to provide written informed consent on the participant's behalf.
  • Participant has a reliable informant (parent or caregiver) who has sufficient past and current knowledge of the subject and will oversee the administration of study medication and accompany the subject to each study visit.
  • Participant and caregiver have reliable means of transportation to attend study visits.

Exclusion Criteria:

  • Chronic medical illness that is not stable or would pose a risk to the participant if he participates in the trial
  • History of clinical seizures within the 12 months preceding study enrollment
  • Known genetic disorder that is presumed to be the cause of autism spectrum disorder (eg., Fragile x syndrome, tuberous sclerosis)
  • Changes to psychopharmacological medications (e.g., stimulants, antidepressants, anxiolytics, antipsychotics) in the 4 weeks preceding study enrollment
  • Significant changes to non-pharmacological treatments for ASD in the 4 weeks preceding study enrollment
  • Chronic treatment with anti-inflammatory agents (e.g., ibuprofen, NSAIDs, corticosteroids)
  • Clinically significant laboratory abnormalities at Screening visit (e.g., AST/ALT> two times the upper normal limits; serum creatinine > 1.2 mg/dl, TSH outside normal limits)
  • Clinically significant findings on physical examination that investigator determines could increase risk of harm from participating in the study
  • Participated in another clinical interventional trial or received an investigational product in the 30 days preceding study enrollment
  • Previous therapeutic trial of sulforaphane or participation in a clinical trial in which sulforaphane was the investigational agent
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 13 Years to 30 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02909959
Other Study ID Numbers  ICMJE 16-2059
5KL2TR001109-05 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: The investigators plan to publish the results of this trial in a peer-reviewed journal and on ClinicalTrials.gov upon completion of the study. No personal identifiable participant data will be included in the reporting of results.
Responsible Party University of North Carolina, Chapel Hill
Study Sponsor  ICMJE University of North Carolina, Chapel Hill
Collaborators  ICMJE North Carolina Translational and Clinical Sciences Institute
Investigators  ICMJE
Principal Investigator: Laura Politte, M.D. University of North Carolina, Chapel Hill
PRS Account University of North Carolina, Chapel Hill
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP