Autism Spectrum DisorderPhase 2NCT02909959
Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
A Phase 2 study testing Sulforaphane in people with Autism Spectrum Disorder and Autistic Disorder, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 13 to 30 years, men only
- Conditions the study is for
- Autism Spectrum Disorder, Autistic Disorder, Neurodevelopmental Disorder
- What is being tested?
- Sulforaphane
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2017to 30 May 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 to 30 years
- Men only
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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)
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Carolina Institute for Developmental Disabilities, University of North Carolina School of Medicine
Carrboro, North Carolina, 27510
About this study
Official title: A Phase II, Randomized, Double-blind, Placebo-controlled Study of Myrosinase-enriched Glucoraphanin, a Sulforaphane Precursor System, in Autism Spectrum Disorder
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.
Read the 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
- Being tested
- Sulforaphane, Placebo
- Keywords
- sulforaphane, glucoraphanin, physiologic effects of drugs
- Medical subject headings
- Autism Spectrum Disorder, Autistic Disorder, Neurodevelopmental Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SulforaphaneDrug
Also called Avmacol, glucoraphanin
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.
PlaceboDrug
Also called Control
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.
| Study group | Role | What they receive |
|---|---|---|
| Sulforaphane | Active comparator | 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 Receives: Drug: Sulforaphane |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Social Responsiveness Scale-2 (SRS-2) Total Score at Baseline
The Social Responsiveness Scale-2 (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). The SRS-2 provides a T-score that is scaled such that the mean is 50 and the SD is 10. Higher scores indicate a higher presence and severity of autistic social impairment. A T-score of 76 or higher is considered "severe". T-scores between 66 and 75 are considered as "moderate". T-scores between 60 and 65 are considered "mild". A T-score below 60 is considered typical. The theoretical range of a T-score is 10 to 90. The actual range of the SRS-2 in this study is 45 to 90.
Measured: Baseline
Social Responsiveness Scale-2 (SRS-2) Total Score at Week 4
The Social Responsiveness Scale-2 (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). The SRS-2 provides a T-score that is scaled such that the mean is 50 and the SD is 10. Higher scores indicate a higher presence and severity of autistic social impairment. A T-score of 76 or higher is considered "severe". T-scores between 66 and 75 are considered as "moderate". T-scores between 60 and 65 are considered "mild". A T-score below 60 is considered typical. The theoretical range of a T-score is 10 to 90. The actual range of the SRS-2 in this study is 45 to 90.
Measured: Week 4
Social Responsiveness Scale-2 (SRS-2) Total Score at Week 8
The Social Responsiveness Scale-2 (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). The SRS-2 provides a T-score that is scaled such that the mean is 50 and the SD is 10. Higher scores indicate a higher presence and severity of autistic social impairment. A T-score of 76 or higher is considered "severe". T-scores between 66 and 75 are considered as "moderate". T-scores between 60 and 65 are considered "mild". A T-score below 60 is considered typical. The theoretical range of a T-score is 10 to 90. The actual range of the SRS-2 in this study is 45 to 90.
Measured: Week 8
Social Responsiveness Scale-2 (SRS-2) Total Score at Week 12
The Social Responsiveness Scale-2 (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). The SRS-2 provides a T-score that is scaled such that the mean is 50 and the SD is 10. Higher scores indicate a higher presence and severity of autistic social impairment. A T-score of 76 or higher is considered "severe". T-scores between 66 and 75 are considered as "moderate". T-scores between 60 and 65 are considered "mild". A T-score below 60 is considered typical. The theoretical range of a T-score is 10 to 90. The actual range of the SRS-2 in this study is 45 to 90.
Measured: Week 12
Social Responsiveness Scale-2 (SRS-2) Total Score at Week 16
The Social Responsiveness Scale-2 (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). The SRS-2 provides a T-score that is scaled such that the mean is 50 and the SD is 10. Higher scores indicate a higher presence and severity of autistic social impairment. A T-score of 76 or higher is considered "severe". T-scores between 66 and 75 are considered as "moderate". T-scores between 60 and 65 are considered "mild". A T-score below 60 is considered typical. The theoretical range of a T-score is 10 to 90. The actual range of the SRS-2 in this study is 45 to 90.
Measured: Week 16
Secondary outcomes (42)
Social Responsiveness Scale-2 (SRS-2) Subscale Score (Social Awareness)
The Social Responsiveness Scale-2 (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). The SRS-2-Social Awareness subscale measures a participant's ability to recognize social cues. This subscale comprises 8 items with scores ranging from 1 to 4 for a total range of scores from 8 to 32. A higher score represents a greater ability to recognize social cues.
Subscales are not diagnostic in nature, but they provide some insight into individual behaviors. This subscale was measured at Baseline, Week 4, Week 8, Week 12, and Week 16.
Measured: Baseline, Week 4, Week 8, Week 12, Week 16
Social Responsiveness Scale-2 (SRS-2) Subscale Score (Social Cognition)
The Social Responsiveness Scale-2 (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). The SRS-2-Social Cognition subscale measures a participant's ability to interpret social behavior. This subscale comprises 12 items with scores ranging from 1 to 4 for a total range of scores from 12 to 48. A higher score represents a greater ability to interpret social behaviors. Subscales are not diagnostic in nature, but they provide some insight into individual behaviors. This subscale was measured at Baseline, Week 4, Week 8, Week 12, and Week 16.
Measured: Baseline, Week 4, Week 8, Week 12, Week 16
Social Responsiveness Scale-2 (SRS-2) Subscale Score (Social Communication)
The Social Responsiveness Scale-2 (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). The SRS-2-Social Communication subscale measures a participant's ability to assess reciprocal communication in social situations. This subscale comprises 22 items with scores ranging from 1 to 4 for a total range of scores from 22 to 88. A higher score represents a greater ability to assess reciprocal communication. Subscales are not diagnostic in nature, but they provide some insight into individual behaviors. This subscale was measured at Baseline, Week 4, Week 8, Week 12, and Week 16.
Measured: Baseline, Week 4, Week 8, Week 12, Week 16
Social Responsiveness Scale-2 (SRS-2) Subscale Score (Social Motivation)
The Social Responsiveness Scale-2 (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). The SRS-2-Social Motivation subscale measures the degree to which a participant is motivated to participate in social interactions. This subscale comprises 11 items with scores ranging from 1 to 4 for a total range of scores from 11 to 44. A higher score represents a greater motivation to participate in social interaction. Subscales are not diagnostic in nature, but they provide some insight into individual behaviors. This subscale was measured at Baseline, Week 4, Week 8, Week 12, and Week 16.
Measured: Baseline, Week 4, Week 8, Week 12, Week 16
Social Responsiveness Scale-2 (SRS-2) Subscale Score (Restricted Interests/Repetitive Behaviors)
The Social Responsiveness Scale-2 (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). The SRS-2-Restricted Interests/Repetitive Behaviors subscale assesses the participant's level of stereotypy and circumscribed interests. This subscale comprises 12 items with scores ranging from 1 to 4 for a total range of scores from 12 to 48. A higher score represents a greater level of stereotypy and circumscribed interests. Subscales are not diagnostic in nature, but they provide some insight into individual behaviors. This subscale was measured at Baseline, Week 4, Week 8, Week 12, and Week 16.
Measured: Baseline, Week 4, Week 8, Week 12, Week 16
Aberrant Behavior Checklist (ABC) Subscale Score (Social Withdrawal)
The Aberrant Behavior Checklist (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. The ABC-Social Withdrawal subscale assesses the participant's level social withdrawal. This subscale comprises 16 items with scores ranging from 0 to 3 for a total range of scores from 0 to 48. A higher score represents a greater level of social withdrawal. This subscale was measured at Baseline, Week 4, Week 8, Week 12, and Week 16.
Measured: Baseline, Week 4, Week 8, Week 12, Week 16
Aberrant Behavior Checklist (ABC) Subscale Scores (Hyperactivity)
The Aberrant Behavior Checklist (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. The ABC-Hyperactivity subscale assesses the participant's level hyperactivity and non-compliance. This subscale comprises 16 items with scores ranging from 0 to 3 for a total range of scores from 0 to 48. A higher score represents a greater level of hyperactivity/non-compliance. This subscale was measured at Baseline, Week 4, Week 8, Week 12, and Week 16.
Measured: Baseline, Week 4, Week 8, Week 12, Week 16
Aberrant Behavior Checklist (ABC) Subscale Score (Inappropriate Speech)
The Aberrant Behavior Checklist (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. The ABC-Inappropriate Speech subscale assesses the participant's use of inappropriate speech. This subscale comprises 4 items with scores ranging from 0 to 3 for a total range of scores from 0 to 12. A higher score represents a greater use of inappropriate speech. This subscale was measured at Baseline, Week 4, Week 8, Week 12, and Week 16.
Measured: Baseline, Week 4, Week 8, Week 12, Week 16
Aberrant Behavior Checklist (ABC) Subscale Score (Stereotypy)
The Aberrant Behavior Checklist (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. The ABC-Stereotypy subscale assesses the participant's level of stereotypic behavior. This subscale comprises 7 items with scores ranging from 0 to 3 for a total range of scores from 0 to 21. A higher score represents a greater level of stereotypic behavior. This subscale was measured at Baseline, Week 4, Week 8, Week 12, and Week 16.
Measured: Baseline, Week 4, Week 8, Week 12, Week 16
Aberrant Behavior Checklist (ABC) Subscale Score (Irritability)
The Aberrant Behavior Checklist (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. The ABC-Irritability subscale assesses the participant's level of irritability. This subscale comprises 15 items with scores ranging from 0 to 3 for a total range of scores from 0 to 45. A higher score represents a greater level of irritability. This subscale was measured at Baseline, Week 4, Week 8, Week 12, and Week 16.
Measured: Baseline, Week 4, Week 8, Week 12, Week 16
Clinical Global Impression-Severity (CGI-S) Score
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). A higher score indicates a higher level of severity of psychopathology. This scale was measured at Baseline, Week 4, Week 8, Week 12, and Week 16.
Measured: Baseline, Week 4, Week 8, Week 12, Week 16
Number of Participants With Clinical Global Impression-Improvement (CGI-I) Score of Much Improved or Very Much Improved
The clinician-rated CGI-Improvement (CGI-I) scale rates overall improvement or worsening of illness (ie, ASD) relative to baseline. The CGI-Improvement (CGI-I) scale rates overall improvement or worsening of illness (ie, ASD) relative to baseline. Possible scores on this scale range from 1-6 with the following assigned values: 1 = "Very Much Improved"; 2 = "Much Improved; 3 = "Minimally improved"; 4 = "No change"; 5 = "Minimally worse"; 6= "Much worse." A higher score indicates worsening of illness (ie, ASD), whereas a lower score indicates improvement of illness. This scale was measured at Week 4, Week 8, Week 12, and Week 16. In this measure, the number of participants in each treatment arm determined by the study physician to be "Much Improved" or "Very Much Improved" (indicative of meaningful clinical improvement) were counted.
Measured: Week 4, Week 8, Week 12, Week 16
Repetitive Behavior Scale-Revised (RBSR) Total Score
The RBS-R is a 43-item, informant-based questionnaire designed to quantify a range of restricted, repetitive behaviors (RRB) observed in ASD. Scores for each item range from 0 = "Behavior does not occur" to 3 = "Behavior occurs and is a severe problem". Thus the total range is 0 to 129. A higher score indicates a higher breadth of repetitive behaviors. This scale was measured at Baseline, Week 4, Week 8, Week 12, and Week 16.
Measured: Baseline, Week 4, Week 8, Week 12, Week 16
Mean Red Blood Cell Value
This measure assesses the red blood cell value as part of the complete blood count measurement. This blood count measure was assessed at Baseline and Week 12.
Measured: Baseline, Week 12
Mean White Blood Cell Value
This measure assesses the white blood cell value as part of the complete blood count measurement. This blood count measure was assessed at Baseline and Week 12.
Measured: Baseline, Week 12
Mean Hemoglobin Value
This measure assesses the hemoglobin value as part of the complete blood count measurement. This blood count measure was assessed at Baseline and Week 12.
Measured: Baseline, Week 12
Mean Hematocrit Value
This measure assesses the hematocrit value as part of the complete blood count measurement. This blood count measure was assessed at Baseline and Week 12.
Measured: Baseline, Week 12
Mean Corpuscular Volume Value
This measure assesses the mean corpuscular volume value as part of the complete blood count measurement. This blood count measure was assessed at Baseline and Week 12.
Measured: Baseline, Week 12
Mean Corpuscular Hemoglobin Value
This measure assesses the mean corpuscular hemoglobin value as part of the complete blood count measurement. This blood count measure was assessed at Baseline and Week 12.
Measured: Baseline, Week 12
Mean Corpuscular Hemoglobin Concentration Value
This measure assesses the mean corpuscular hemoglobin concentration value as part of the complete blood count measurement. This blood count measure was assessed at Baseline and Week 12.
Measured: Baseline, Week 12
Mean Red Blood Cell Distribution Width Value
This measure assesses the red blood cell distribution width value as part of the complete blood count measurement. This blood count measure was assessed at Baseline and Week 12.
Measured: Baseline, Week 12
Mean Platelets Value
This measure assesses the platelets value as part of the complete blood count measurement. This blood count measure was assessed at Baseline and Week 12.
Measured: Baseline, Week 12
Mean Absolute Neutrophils Value
This measure assesses the absolute neutrophils value as part of the complete blood count measurement. This blood count measure was assessed at Baseline and Week 12.
Measured: Baseline, Week 12
Mean Absolute Lymphocytes Value
This measure assesses the absolute lymphocytes value as part of the complete blood count measurement. This blood count measure was assessed at Baseline and Week 12.
Measured: Baseline, Week 12
Mean Absolute Monocytes Value
This measure assesses the absolute monocytes value as part of the complete blood count measurement. This blood count measure was assessed at Baseline and Week 12.
Measured: Baseline, Week 12
Mean Absolute Eosinophils Value
This measure assesses the absolute eosinophils value as part of the complete blood count measurement. This blood count measure was assessed at Baseline and Week 12.
Measured: Baseline, Week 12
Mean Absolute Basophils Value
This measure assesses the absolute basophils value as part of the complete blood count measurement. This blood count measure was assessed at Baseline and Week 12.
Measured: Baseline, Week 12
Mean Serum Chemistries (Sodium)
This measure assesses the change in the patient's sodium levels. This serum chemistry level was measured at Baseline and Week 12.
Measured: Baseline, Week 12
Mean Serum Chemistries (Potassium)
This measure assesses the change in the patient's potassium levels. This serum chemistry level was measured at Baseline and Week 12.
Measured: Baseline, Week 12
Mean Serum Chemistries (Chloride)
This measure assesses the change in the patient's chloride levels. This serum chemistry level was measured at Baseline and Week 12.
Measured: Baseline, Week 12
Mean Serum Chemistries (Bicarbonate)
This measure assesses the change in the patient's bicarbonate levels. This serum chemistry level was measured at Baseline and Week 12.
Measured: Baseline, Week 12
Mean Serum Chemistries (Blood Urea Nitrogen)
This measure assesses the change in the patient's blood urea nitrogen levels. This serum chemistry level was measured at Baseline and Week 12.
Measured: Baseline, Week 12
Mean Serum Chemistries (Creatinine)
This measure assesses the change in the patient's creatinine levels. This serum chemistry level was measured at Baseline and Week 12.
Measured: Baseline, Week 12
Mean Serum Chemistries (Glucose)
This measure assesses the change in the patient's glucose levels. This serum chemistry level was measured at Baseline and Week 12.
Measured: Baseline, Week 12
Mean Liver Function Tests Values (Alanine Transaminase)
This measure assesses the change in the patient's level of liver function through measure of alanine transaminase (ALT). This liver function test value was measured at Baseline and Week 12.
Measured: Baseline, Week 12
Mean Liver Function Tests Values (Aspartate Transaminase)
This measure assesses the change in the patient's level of liver function through measure of aspartate transaminase. This liver function test value was measured at Baseline and Week 12.
Measured: Baseline, Week 12
Mean Liver Function Tests Values (Total Bilirubin)
This measure assesses the change in the patient's level of liver function through measure of total bilirubin. This liver function test value was measured at Baseline and Week 12.
Measured: Baseline, Week 12
Mean Value of Thyroid Stimulating Hormone (TSH)
This measure assesses the change in the patient's value of thyroid stimulating hormone. This hormone value was measured at Baseline and Week 12.
Measured: Baseline, Week 12
Least Squares Mean of Vital Signs (Weight)
This measure assesses the change in the patient's weight (lbs). This vital sign was measured at Baseline, Week 4, Week 8, Week 12, and Week 16.
Measured: Baseline, Week 4, Week 8, Week 12, Week 16
Least Squares Mean of Vital Signs (Height)
This measure assesses the change in the patient's height (centimeters). This vital sign was measured at Baseline, Week 4, Week 8, Week 12, and Week 16.
Measured: Baseline, Week 4, Week 8, Week 12, Week 16
Least Squares Mean of Vital Signs (Blood Pressure)
This measure assesses the change in the patient's systolic and diastolic blood pressure. This vital sign was measured at Baseline, Week 4, Week 8, Week 12, and Week 16.
Measured: Baseline, Week 4, Week 8, Week 12, Week 16
Least Squares Mean of Vital Signs (Heart Rate)
This measure assesses the change in the patient's heart rate (beats per minute). This vital sign was measured at Baseline, Week 4, Week 8, Week 12, and Week 16.
Measured: Baseline, Week 4, Week 8, Week 12, Week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2016 (estimated)
- Study start1 Mar 2017
- Primary completion30 May 2019
- Study completion30 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Autism Spectrum DisorderStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- North Carolina Translational and Clinical Sciences Institute
- Responsible party
- Sponsor
- Investigators
- Laura Politte, M.D., Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02909959
- Sponsor's protocol ID
- 16-2059
- Other IDs
- 5KL2TR001109-05
- Status last verified
- Jun 2019
- First submitted
- 7 Sep 2016
- Last updated
- 4 Jun 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Randomized, Double-blind, Placebo-controlled Study of Myrosinase-enriched Glucoraphanin, a Sulforaphane Precursor System, in Autism Spectrum Disorder
- ClinicalTrials.gov ID
- NCT02909959
- Acronym / sponsor ID
- 16-2059
- Conditions
- Autism Spectrum Disorder, Autistic Disorder, Neurodevelopmental Disorder, Childhood Developmental Disorders, Pervasive
- Keywords
- sulforaphane, glucoraphanin, physiologic effects of drugs
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- North Carolina Translational and Clinical Sciences Institute
- Study start
- 1 Mar 2017 (actual)
- Primary completion
- 30 May 2019 (actual)
- Study completion
- 30 May 2019 (actual)
- First posted
- 21 Sep 2016 (estimated)
- Results
- Posted 15 May 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sulforaphane | Active comparator | Drug: SulforaphaneParticipants 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 |
| Placebo | Placebo comparator | Drug: PlaceboParticipants 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. |
Who may qualify
- Ages
- 13 to 30 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SulforaphaneAlso: Avmacol, glucoraphaninThe 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. | Drug | Sulforaphane |
| PlaceboAlso: ControlPlacebo 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. | Drug | Placebo |
Primary outcome
Social Responsiveness Scale-2 (SRS-2) Total Score at Baseline
Time frame: Baseline
The Social Responsiveness Scale-2 (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). The SRS-2 provides a T-score that is scaled such that the mean is 50 and the SD is 10. Higher scores indicate a higher presence and severity of autistic social impairment. A T-score of 76 or higher is considered "severe". T-scores between 66 and 75 are considered as "moderate". T-scores between 60 and 65 are considered "mild". A T-score below 60 is considered typical. The theoretical range of a T-score is 10 to 90. The actual range of the SRS-2 in this study is 45 to 90.
Social Responsiveness Scale-2 (SRS-2) Total Score at Week 4
Time frame: Week 4
The Social Responsiveness Scale-2 (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). The SRS-2 provides a T-score that is scaled such that the mean is 50 and the SD is 10. Higher scores indicate a higher presence and severity of autistic social impairment. A T-score of 76 or higher is considered "severe". T-scores between 66 and 75 are considered as "moderate". T-scores between 60 and 65 are considered "mild". A T-score below 60 is considered typical. The theoretical range of a T-score is 10 to 90. The actual range of the SRS-2 in this study is 45 to 90.
Social Responsiveness Scale-2 (SRS-2) Total Score at Week 8
Time frame: Week 8
The Social Responsiveness Scale-2 (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). The SRS-2 provides a T-score that is scaled such that the mean is 50 and the SD is 10. Higher scores indicate a higher presence and severity of autistic social impairment. A T-score of 76 or higher is considered "severe". T-scores between 66 and 75 are considered as "moderate". T-scores between 60 and 65 are considered "mild". A T-score below 60 is considered typical. The theoretical range of a T-score is 10 to 90. The actual range of the SRS-2 in this study is 45 to 90.
Social Responsiveness Scale-2 (SRS-2) Total Score at Week 12
Time frame: Week 12
The Social Responsiveness Scale-2 (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). The SRS-2 provides a T-score that is scaled such that the mean is 50 and the SD is 10. Higher scores indicate a higher presence and severity of autistic social impairment. A T-score of 76 or higher is considered "severe". T-scores between 66 and 75 are considered as "moderate". T-scores between 60 and 65 are considered "mild". A T-score below 60 is considered typical. The theoretical range of a T-score is 10 to 90. The actual range of the SRS-2 in this study is 45 to 90.
Social Responsiveness Scale-2 (SRS-2) Total Score at Week 16
Time frame: Week 16
The Social Responsiveness Scale-2 (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). The SRS-2 provides a T-score that is scaled such that the mean is 50 and the SD is 10. Higher scores indicate a higher presence and severity of autistic social impairment. A T-score of 76 or higher is considered "severe". T-scores between 66 and 75 are considered as "moderate". T-scores between 60 and 65 are considered "mild". A T-score below 60 is considered typical. The theoretical range of a T-score is 10 to 90. The actual range of the SRS-2 in this study is 45 to 90.
42 secondary outcomes
Social Responsiveness Scale-2 (SRS-2) Subscale Score (Social Awareness)
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16
Social Responsiveness Scale-2 (SRS-2) Subscale Score (Social Cognition)
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16
Social Responsiveness Scale-2 (SRS-2) Subscale Score (Social Communication)
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16
Social Responsiveness Scale-2 (SRS-2) Subscale Score (Social Motivation)
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16
Social Responsiveness Scale-2 (SRS-2) Subscale Score (Restricted Interests/Repetitive Behaviors)
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16
Aberrant Behavior Checklist (ABC) Subscale Score (Social Withdrawal)
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16
Aberrant Behavior Checklist (ABC) Subscale Scores (Hyperactivity)
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16
Aberrant Behavior Checklist (ABC) Subscale Score (Inappropriate Speech)
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16
Aberrant Behavior Checklist (ABC) Subscale Score (Stereotypy)
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16
Aberrant Behavior Checklist (ABC) Subscale Score (Irritability)
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16
Clinical Global Impression-Severity (CGI-S) Score
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16
Number of Participants With Clinical Global Impression-Improvement (CGI-I) Score of Much Improved or Very Much Improved
Time frame: Week 4, Week 8, Week 12, Week 16
Repetitive Behavior Scale-Revised (RBSR) Total Score
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16
Mean Red Blood Cell Value
Time frame: Baseline, Week 12
Mean White Blood Cell Value
Time frame: Baseline, Week 12
Mean Hemoglobin Value
Time frame: Baseline, Week 12
Mean Hematocrit Value
Time frame: Baseline, Week 12
Mean Corpuscular Volume Value
Time frame: Baseline, Week 12
Mean Corpuscular Hemoglobin Value
Time frame: Baseline, Week 12
Mean Corpuscular Hemoglobin Concentration Value
Time frame: Baseline, Week 12
Mean Red Blood Cell Distribution Width Value
Time frame: Baseline, Week 12
Mean Platelets Value
Time frame: Baseline, Week 12
Mean Absolute Neutrophils Value
Time frame: Baseline, Week 12
Mean Absolute Lymphocytes Value
Time frame: Baseline, Week 12
Mean Absolute Monocytes Value
Time frame: Baseline, Week 12
Mean Absolute Eosinophils Value
Time frame: Baseline, Week 12
Mean Absolute Basophils Value
Time frame: Baseline, Week 12
Mean Serum Chemistries (Sodium)
Time frame: Baseline, Week 12
Mean Serum Chemistries (Potassium)
Time frame: Baseline, Week 12
Mean Serum Chemistries (Chloride)
Time frame: Baseline, Week 12
Mean Serum Chemistries (Bicarbonate)
Time frame: Baseline, Week 12
Mean Serum Chemistries (Blood Urea Nitrogen)
Time frame: Baseline, Week 12
Mean Serum Chemistries (Creatinine)
Time frame: Baseline, Week 12
Mean Serum Chemistries (Glucose)
Time frame: Baseline, Week 12
Mean Liver Function Tests Values (Alanine Transaminase)
Time frame: Baseline, Week 12
Mean Liver Function Tests Values (Aspartate Transaminase)
Time frame: Baseline, Week 12
Mean Liver Function Tests Values (Total Bilirubin)
Time frame: Baseline, Week 12
Mean Value of Thyroid Stimulating Hormone (TSH)
Time frame: Baseline, Week 12
Least Squares Mean of Vital Signs (Weight)
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16
Least Squares Mean of Vital Signs (Height)
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Laura Politte, M.D. principal investigator
University of North Carolina, Chapel Hill
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sulforaphane in people with Autism Spectrum Disorder and Autistic Disorder, run by University of North Carolina, Chapel Hill at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 May 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Social Responsiveness Scale-2 (SRS-2) Total Score at Baseline (time frame: Baseline). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2020.