Sulforaphane-rich Broccoli Sprout Extract for Autism

This study has been completed.
Sponsor:
Collaborator:
Johns Hopkins University
Information provided by (Responsible Party):
Andrew Zimmerman, University of Massachusetts, Worcester
ClinicalTrials.gov Identifier:
NCT01474993
First received: November 8, 2011
Last updated: December 11, 2013
Last verified: December 2013

November 8, 2011
December 11, 2013
December 2011
November 2013   (final data collection date for primary outcome measure)
Change from screening and baseline in Social Responsiveness Scale (SRS) at 4 weeks, 10 weeks, 18 weeks and 22 weeks [ Time Frame: Screening, baseline, 4 weeks, 10 weeks, 18 weeks and 22 weeks ] [ Designated as safety issue: No ]
Social Responsiveness Scale (SRS), a 65 point scale covering 5 treatment subscales focusing on the social communication domain of ASD as observed in natural (non-clinical) settings. The questionnaire may be completed in 15-20 minutes by a trained parent/guardian or teacher.
Same as current
Complete list of historical versions of study NCT01474993 on ClinicalTrials.gov Archive Site
  • Change from screening visit in liver function tests (AST/ALT) at 4 weeks, 18 weeks and 22 weeks [ Time Frame: screening, 4 weeks, 18 weeks, 22 weeks ] [ Designated as safety issue: Yes ]
    AST/ALT
  • Change from screening visit in renal function tests (serum creatinine) at 4 weeks, 18 weeks and 22 weeks [ Time Frame: Screening, 4 weeks, 18 weeks, 22 weeks ] [ Designated as safety issue: Yes ]
    Serum creatinine
  • Change from screening visit in thyroid function tests (TSH) at 4 weeks, 18 weeks and 22 weeks [ Time Frame: Screening, 4 weeks, 18 weeks, 22 weeks ] [ Designated as safety issue: Yes ]
    TSH
  • Change from screening visit in complete blood counts at 4 weeks, 18 weeks and 22 weeks [ Time Frame: Screening, 4 weeks, 18 weeks, 22 weeks ] [ Designated as safety issue: Yes ]
  • Change from screening and baseline in Urinary Isoprostane F2α-VI levels at 24 hours after first dose, at 4 weeks, 10 weeks, 18 weeks and 22 weeks [ Time Frame: Screening, baseline, 24 hours after first dose of study medication, 4 weeks, 10 weeks, 18 weeks, 22 weeks ] [ Designated as safety issue: No ]
  • Change from the screening visit in Heat Shock Protein gene expression (relative maximum gene and protein expression) at 24 hours after first dose, 18 weeks and 22 weeks [ Time Frame: Screening, 24 hours after first dose of study medication, 18 weeks, 22 weeks ] [ Designated as safety issue: No ]
  • Change from screening and baseline in Clinical Global Impression Autism - Severity (CGI-S) Scale at 4 weeks, 10 weeks, 18 weeks and 22 weeks [ Time Frame: Screening, baseline, 4 weeks, 10 weeks, 18 weeks, 22 weeks ] [ Designated as safety issue: No ]
    Clinical Global Impression Autism - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's autism symptoms at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis.
  • Change from screening and baseline in Clinical Global Impression Autism - Improvement Scale (CGI-I) at 4 weeks, 10 weeks, 18 weeks and 22 weeks [ Time Frame: Screening, baseline, 4 weeks, 10 weeks, 18 weeks, 22 weeks ] [ Designated as safety issue: No ]
    Clinical Global Impression Autism - Improvement scale (CGI-I) is a 7 point scale that requires the clinician to assess how much the patient's illness (in this case, autism) has improved or worsened relative to a baseline state at the beginning of the intervention
  • Change from screening and baseline in Aberrant Behavior Checklist (ABC) at 4 weeks, 10 weeks, 18 weeks and 22 weeks [ Time Frame: Screening, baseline, 4 weeks, 10 weeks, 18 weeks, 22 weeks ] [ Designated as safety issue: No ]
    The Aberrant Behavior Checklist (ABC) is a 58-item rating scale developed for persons with developmental disabilities. It is designed to be used with clients living in the community, often used to assess medication effects on persons with developmental disabilities. Administration Time: 10 - 15 minutes
Same as current
Not Provided
Not Provided
 
Sulforaphane-rich Broccoli Sprout Extract for Autism
Sulforaphane-rich Broccoli Sprout Extract for Autism

The primary objectives of this study are to answer whether there is evidence of measurable effects on social responsiveness (primary outcome) and other behavioral symptoms after treatment of autistic male adolescents and adults with orally administered sulforaphane-rich Broccoli Sprout Extract (efficacy). The secondary objectives of this study are to answer whether treatment of male adolescents and adults with autism using orally administered sulforaphane-rich Broccoli Sprout Extract within a specified dose range is safe (toxicity); treatment with sulforaphane-rich Broccoli Sprout Extract is well tolerated (side effects and adverse events); key cellular biomarkers support the hypothesized mechanisms (proof of principle).

Behavioral improvements occur transiently during febrile illnesses in autism, and include decreased repetitive behaviors and improved speech. These changes have been recorded in 38% of autistic children in a clinical survey and 83% in an observational study, respectively. The cellular basis for this "fever effect" is unknown but is likely to involve heat shock proteins (HSP) and cellular stress responses (CSR) that lead to changes in synaptic function and network connectivity.

Sulforaphane (1-isothiocyanato-4R- (methylsulfinyl)butane) is an isothiocyanate that is delivered by lyophilized extracts of 3-day-old broccoli sprouts. Broccoli sprouts are widely consumed as a food item all over the world by very large numbers of individuals, without any reports of adverse effects. Our preliminary work in vitro shows that sulforaphane stimulates HSP and mitochondrial biogenesis in several genetic disorders.

This study of sulforaphane-rich Broccoli Sprout Extract in autism is a randomized, double-blinded, placebo-controlled, phase II single site trial, designed to ensure safety and obtain efficacy data, with a focus on changes in social responsiveness, a core feature of autism. Its hybrid design, incorporating double masking, placebo control, and randomization, enhances the robustness of early outcome data. The study duration will be 2 years. Recruitment of subjects will be 50% by 8 months and complete by 14 months. All subjects in the study will be followed for 22 weeks. Treatment (18 weeks) will be started as patients are entered into the study and receive baseline testing. All treatment will be completed by 20 months and data analysis and presentation of results by 24 months.

Forty-five male adolescents (13-18 years) and adults (19-30 years) with autism will be randomly assigned to receive either sulforaphane-rich Broccoli Sprout Extract (n = 30) or placebo (n = 15). The 2:1 randomization schedule will be produced by the study statistician using permuted random blocks and stratification by history of positive behavioral effects of fever. Treatment assignments will be performed by the research pharmacy at MGH. Females will be excluded for homogeneity of the sample and because males have higher incidence of autism than females (4:1). We will seek to enroll up to 50% of the subjects having a history of positive behavioral effects of fever, which will be recorded from caregivers' recall of incidents and graded on the CGI-Improvement (CGI-I) 7-point scale.

There will be in total 7 study visits for each subject: the screening visit, enrollment visit, a blood draw visit at 24 hours after the first dose of study medication (for mitochondrial/heat shock protein analysis), 4 week (follow-up) visit, 10 week (follow-up) visit, 18 week visit (last treatment visit), and the final closeout visit one month after the study drug stops (22 weeks). Even though the treatment will stop at 18 weeks, we will follow subjects for additional 4 weeks after study medication stops (the 22 week visit) to ensure safety after study drug stops. Additional visits may be conducted in case any side effects are reported at any stage of the study.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Autism
  • Drug: Sulforaphane-rich Broccoli Sprout Extract

    30 subjects will be randomly selected to receive sulforaphane-rich Broccoli Sprout Extract. The medication will be supplied and dispensed as No.1 size gelcaps (each gelcap containing ~ 250 mg sulforaphane rich Broccoli Sprout Extract, equivalent to ~ 50 µmol of sulforaphane). The dosage of sulforaphane will depend on subject's body weight:

    1. Subjects with body weight less than 101 lbs will receive ~ 50 micromol sulforaphane per day (1 gelcap to be taken once a day)
    2. Subjects with body weight 101 lbs to 199 lbs will receive ~ 100 micromol sulforaphane per day (2 gelcaps to be taken once a day)
    3. Subjects with bidy weight > 199 lbs will receive ~ 150 micromol sulforaphane per day (3 gelcaps to be taken once a day)
  • Drug: Placebo
    15 subjects will be randomly selected to receive inactive placebo (Gelcaps identical in appearance to that of active medication and containing microcrystalline cellulose)
  • Placebo Comparator: Placebo
    15 subjects will be randomly selected to receive inactive placebo (Gelcaps identical in appearance to that of active medication and containing microcrystalline cellulose).
    Intervention: Drug: Placebo
  • Experimental: Sulforaphane-rich Broccoli Sprout Extract
    30 subjects will be randomly selected to receive sulforaphane-rich Broccoli Sprout Extract.
    Intervention: Drug: Sulforaphane-rich Broccoli Sprout Extract
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
44
November 2013
November 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Autism diagnosis. Quantitative autism traits and severity for diagnosis of autism will be assessed using the ADOS-G (Modules 1-4 and Severity), Social Responsiveness Scale (SRS; child and adult forms), Clinical Global Impression-Severity (CGI-S) and Aberrant Behavior Checklist-Withdrawal subscale (ABC-W).

Exclusion Criteria:

  • Absence of a parent or legal guardian and consent
  • Unavailability for all visits and adherence to study regimen
  • Seizure within 2 years of screening
  • Impaired renal function (serum creatinine > 1.2 mg/dl), impaired hepatic function (AST/ALT > 2x upper limit of normal), impaired thyroid function (TSH outside normal limits)
  • Current infection or treatment with antibiotics; AND
  • Chronic medical disorder (e.g., cardiovascular disease, stroke or diabetes) or major surgery within 3 months prior to enrollment.
  • A diagnosis of autism spectrum disorder other than autism, for example, Asperger's, PDD-NOS etc.
Male
13 Years to 30 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01474993
2011P002221
Yes
Andrew Zimmerman, University of Massachusetts, Worcester
University of Massachusetts, Worcester
Johns Hopkins University
Principal Investigator: Andrew W. Zimmerman, M.D. Massachusetts General Hospital
University of Massachusetts, Worcester
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP