Sulforaphane-rich Broccoli Sprout Extract for Autism
Condition: Autism
MeSH terms: Autistic Disorder
Study type: Interventional
Phase: Phase 2

Summary: 
      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).
    

Detailed description: 
      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.
    

Intervention name(s): Sulforaphane-rich Broccoli Sprout Extract; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 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:
Subjects with body weight less than 101 lbs will receive ~ 50 micromol sulforaphane per day (1 gelcap to be taken once a day)
Subjects with body weight 101 lbs to 199 lbs will receive ~ 100 micromol sulforaphane per day (2 gelcaps to be taken once a day)
Subjects with bidy weight > 199 lbs will receive ~ 150 micromol sulforaphane per day (3 gelcaps to be taken once a day); 15 subjects will be randomly selected to receive inactive placebo (Gelcaps identical in appearance to that of active medication and containing microcrystalline cellulose)
Intervention MeSH terms: Sulforaphane
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment