Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder

NCT ID: NCT02909959

Last Updated: 2020-06-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-01
• Study Completion Date: 2019-05-30

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.

Conditions

Autism Spectrum Disorder; Autistic Disorder; Neurodevelopmental Disorder; Childhood Developmental Disorders, Pervasive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Sulforaphane

Intervention Type: DRUG

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

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Avmacol; glucoraphanin; Control

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

• Minimum Eligible Age: 13 Years
• Maximum Eligible Age: 30 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

North Carolina Translational and Clinical Sciences Institute

OTHER

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Laura Politte, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Locations

Carolina Institute for Developmental Disabilities, University of North Carolina School of Medicine

Carrboro, North Carolina, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

5KL2TR001109-05

Identifier Type: NIH

Identifier Source: secondary_id

View Link

16-2059

Identifier Type: -

Identifier Source: org_study_id