This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder

This study is currently recruiting participants.
See Contacts and Locations
Verified April 2017 by University of North Carolina, Chapel Hill
Sponsor:
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT02909959
First received: September 7, 2016
Last updated: April 26, 2017
Last verified: April 2017
  Purpose
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.

Condition Intervention Phase
Autism Spectrum Disorder Autistic Disorder Neurodevelopmental Disorder Childhood Developmental Disorders, Pervasive Drug: Sulforaphane Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II, Randomized, Double-blind, Placebo-controlled Study of Myrosinase-enriched Glucoraphanin, a Sulforaphane Precursor System, in Autism Spectrum Disorder

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • 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).


Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 54
Actual Study Start Date: March 1, 2017
Estimated Study Completion Date: November 2019
Estimated Primary Completion Date: November 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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
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.
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

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.

  Eligibility

Ages Eligible for Study:   13 Years to 30 Years   (Child, Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02909959

Contacts
Contact: Laura Politte, M.D. 919-445-4160 laura.politte@cidd.unc.edu
Contact: Morgan Parlier, MSW 919-843-8122 morgan.parlier@cidd.unc.edu

Locations
United States, North Carolina
Carolina Institute for Developmental Disabilities, University of North Carolina School of Medicine Recruiting
Carrboro, North Carolina, United States, 27510
Contact: Laura Politte, M.D.    919-445-4160    laura.politte@cidd.unc.edu   
Contact: Morgan Parlier, MSW    919-843-8122    morgan.parlier@cidd.unc.edu   
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Investigators
Principal Investigator: Laura Politte, M.D. University of North Carolina, Chapel Hill
  More Information

Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT02909959     History of Changes
Other Study ID Numbers: 16-2059
Study First Received: September 7, 2016
Last Updated: April 26, 2017
Individual Participant Data (IPD) Sharing Statement:
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.

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of North Carolina, Chapel Hill:
sulforaphane
glucoraphanin
physiologic effects of drugs

Additional relevant MeSH terms:
Disease
Autistic Disorder
Autism Spectrum Disorder
Child Development Disorders, Pervasive
Developmental Disabilities
Neurodevelopmental Disorders
Pathologic Processes
Mental Disorders
Sulforafan
Anticarcinogenic Agents
Protective Agents
Physiological Effects of Drugs
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 20, 2017