Clinical trial NCT02909959: Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
Official title: A Phase II, Randomized, Double-blind, Placebo-controlled Study of Myrosinase-enriched Glucoraphanin, a Sulforaphane Precursor System, in Autism Spectrum Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Autism Spectrum Disorder
Autistic Disorder
Neurodevelopmental Disorder
Childhood Developmental Disorders, Pervasive
Keywords: sulforaphane
glucoraphanin
physiologic effects of drugs
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: North Carolina Translational and Clinical Sciences Institute
First posted: 2016-09-21
Enrollment: 48
Sex: MALE
Minimum age (years): 13
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Social Responsiveness Scale-2 (SRS-2) Total Score at Baseline
timeFrame: Baseline
measure: Social Responsiveness Scale-2 (SRS-2) Total Score at Week 4
timeFrame: Week 4
measure: Social Responsiveness Scale-2 (SRS-2) Total Score at Week 8
timeFrame: Week 8
measure: Social Responsiveness Scale-2 (SRS-2) Total Score at Week 12
timeFrame: Week 12
measure: Social Responsiveness Scale-2 (SRS-2) Total Score at Week 16
timeFrame: Week 16
Secondary outcomes:
measure: Social Responsiveness Scale-2 (SRS-2) Subscale Score (Social Awareness)
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 16
measure: Social Responsiveness Scale-2 (SRS-2) Subscale Score (Social Cognition)
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 16
measure: Social Responsiveness Scale-2 (SRS-2) Subscale Score (Social Communication)
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 16
measure: Social Responsiveness Scale-2 (SRS-2) Subscale Score (Social Motivation)
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 16
measure: Social Responsiveness Scale-2 (SRS-2) Subscale Score (Restricted Interests/Repetitive Behaviors)
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 16
measure: Aberrant Behavior Checklist (ABC) Subscale Score (Social Withdrawal)
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 16
measure: Aberrant Behavior Checklist (ABC) Subscale Scores (Hyperactivity)
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 16
measure: Aberrant Behavior Checklist (ABC) Subscale Score (Inappropriate Speech)
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 16
measure: Aberrant Behavior Checklist (ABC) Subscale Score (Stereotypy)
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 16
measure: Aberrant Behavior Checklist (ABC) Subscale Score (Irritability)
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 16
measure: Clinical Global Impression-Severity (CGI-S) Score
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 16
measure: Number of Participants With Clinical Global Impression-Improvement (CGI-I) Score of Much Improved or Very Much Improved
timeFrame: Week 4, Week 8, Week 12, Week 16
measure: Repetitive Behavior Scale-Revised (RBSR) Total Score
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 16
measure: Mean Red Blood Cell Value
timeFrame: Baseline, Week 12
measure: Mean White Blood Cell Value
timeFrame: Baseline, Week 12
measure: Mean Hemoglobin Value
timeFrame: Baseline, Week 12
measure: Mean Hematocrit Value
timeFrame: Baseline, Week 12
measure: Mean Corpuscular Volume Value
timeFrame: Baseline, Week 12
measure: Mean Corpuscular Hemoglobin Value
timeFrame: Baseline, Week 12
measure: Mean Corpuscular Hemoglobin Concentration Value
timeFrame: Baseline, Week 12
measure: Mean Red Blood Cell Distribution Width Value
timeFrame: Baseline, Week 12
measure: Mean Platelets Value
timeFrame: Baseline, Week 12
measure: Mean Absolute Neutrophils Value
timeFrame: Baseline, Week 12
measure: Mean Absolute Lymphocytes Value
timeFrame: Baseline, Week 12
measure: Mean Absolute Monocytes Value
timeFrame: Baseline, Week 12
measure: Mean Absolute Eosinophils Value
timeFrame: Baseline, Week 12
measure: Mean Absolute Basophils Value
timeFrame: Baseline, Week 12
measure: Mean Serum Chemistries (Sodium)
timeFrame: Baseline, Week 12
measure: Mean Serum Chemistries (Potassium)
timeFrame: Baseline, Week 12
measure: Mean Serum Chemistries (Chloride)
timeFrame: Baseline, Week 12
measure: Mean Serum Chemistries (Bicarbonate)
timeFrame: Baseline, Week 12
measure: Mean Serum Chemistries (Blood Urea Nitrogen)
timeFrame: Baseline, Week 12
measure: Mean Serum Chemistries (Creatinine)
timeFrame: Baseline, Week 12
measure: Mean Serum Chemistries (Glucose)
timeFrame: Baseline, Week 12
measure: Mean Liver Function Tests Values (Alanine Transaminase)
timeFrame: Baseline, Week 12
measure: Mean Liver Function Tests Values (Aspartate Transaminase)
timeFrame: Baseline, Week 12
measure: Mean Liver Function Tests Values (Total Bilirubin)
timeFrame: Baseline, Week 12
measure: Mean Value of Thyroid Stimulating Hormone (TSH)
timeFrame: Baseline, Week 12
measure: Least Squares Mean of Vital Signs (Weight)
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 16
measure: Least Squares Mean of Vital Signs (Height)
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 16
measure: Least Squares Mean of Vital Signs (Blood Pressure)
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 16
measure: Least Squares Mean of Vital Signs (Heart Rate)
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 16
Other outcomes:
Locations:
city: Carrboro
country: United States
facility: Carolina Institute for Developmental Disabilities, University of North Carolina School of Medicine
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Laura Politte, M.D.
role: PRINCIPAL_INVESTIGATOR
References: