Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
|Autism Spectrum Disorder Autistic Disorder Neurodevelopmental Disorder Childhood Developmental Disorders, Pervasive||Drug: Sulforaphane Drug: Placebo||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: 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|
- 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).
- 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 ]
|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)|
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
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.
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.
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
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02909959
|Contact: Laura Politte, M.D.||email@example.com|
|Contact: Morgan Parlier, MSWfirstname.lastname@example.org|
|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 email@example.com|
|Contact: Morgan Parlier, MSW 919-843-8122 firstname.lastname@example.org|
|Principal Investigator:||Laura Politte, M.D.||University of North Carolina, Chapel Hill|