Clinical trial NCT01474993
Conditions: Autism
Sponsor: Andrew Zimmerman
Start date: 2011-12-01; Completion date: 2013-11-01
Enrollment: 44 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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.

Arms: arm 1: inactive placebo. arm 2: sulforaphane-rich Broccoli Sprout Extract.
Interventions: intervention 1: Sulforaphane-rich Broccoli Sprout Extract intervention 2: Placebo
Intervention descriptions: intervention 1: 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) intervention 2: 15 subjects will be randomly selected to receive inactive placebo (Gelcaps identical in appearance to that of active medication and containing microcrystalline cellulose)

Protocol documents: