Sulforaphane Treatment of Children With Autism Spectrum Disorder (ASD)
Condition: Autism Spectrum Disorder
MeSH terms: Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      ASD is a diverse disorder starting in early childhood and characterized by social
      communication impairment as well as restricted interests and repetitive behaviors. It affects
      1:68 children and is an enormous medical and economic problem for which there is no
      established, mechanism-based treatment. Sulforaphane is an isothiocyanate derived from
      broccoli, and has potent activity in transcriptionally up-regulating genes that control
      mechanisms whereby aerobic cells protect themselves against oxidative stress, mitochondrial
      dysfunction, and inflammation.

      This study is a clinical trial of oral sulforaphane (as broccoli seed powder) in 50 boys and
      girls (3-12 years) with ASD in 3 phases over 36 weeks. In Phase 1, 25 children will receive
      active drug and 25 will receive placebo for 15 weeks; in Phase 2, all children will receive
      sulforaphane from 15-30 weeks; in Phase 3, children will receive no treatment for 6 weeks.
      Study visits will take place at screening, 7, 15, 22, 30 and 36 weeks, when the Ohio Autism
      Clinical Clinical Impressions Scale - Severity and Improvement (OACIS-S and OACIS-I),
      Aberrant Behavior Checklist (ABC) and Social Responsiveness Scale (SRS) will be recorded.
      Children will be monitored with physical examinations and for toxicity with clinical
      laboratory studies and examine possible biomarkers: Nuclear factor-erythroid factor 2 (Nrf2),
      oxidative stress and mitochondrial function, the mechanistic target of rapamycin (mTOR)
      pathway and cytokine expression. In addition, prior to the main clinical trial, a pilot study
      will be carried out in 10 children with ASD, 6-12 years of age, who will receive
      sulforaphane, 2.2 micromoles/kg daily for 14 days. Blood and urine samples before and at the
      end of treatment will be collected, in order to measure several parameters that are likely to
      demonstrate expected effects of sulforaphane, to standardize the assays and procedures, and
      to determine the most effective measures.
    

Detailed description: 
      Background: ASD is a diverse disorder starting in early childhood and characterized by social
      communication impairment as well as restricted interests and repetitive behaviors. It affects
      1:68 children and is an enormous medical and economic problem for which there is no
      established, mechanism-based treatment. Sulforaphane is an isothiocyanate derived from
      broccoli, and has potent activity in transcriptionally up-regulating genes that control
      mechanisms whereby aerobic cells protect themselves against oxidative stress, mitochondrial
      dysfunction, and inflammation.

      Hypothesis: Based on the observation that fever is frequently associated with behavioral
      improvements in children with ASD, it is hypothesized that sulforaphane might lead to
      functional improvements in ASD because it can up-regulate cell-protective responses, such as
      heat shock proteins and related mechanisms that are also up-regulated during fever. These
      mechanisms are central to multiple cellular processes in the central nervous system,
      including synaptic transmission, and may improve long-range cerebral cortical connectivity,
      which is depressed in ASD.

      Specific aims: The 3 specific aims in this study are: 1) To determine if there are measurable
      effects on social responsiveness and problem behaviors during treatment of children with
      sulforaphane; 2) To determine if treatment with sulforaphane in children is safe and well
      tolerated; and 3) To elucidate cellular biomarkers that respond to treatment with
      sulforaphane.

      Design: This is a randomized, double blind, single-arm crossover phase 1/2 clinical trial of
      orally administered sulforaphane (as broccoli seed powder) in 50 boys and girls (3-12 years)
      with ASD in 3 phases over 36 weeks.

      In Phase 1, 25 children will receive active drug and 25 will receive placebo for 15 weeks; in
      Phase 2, all children will receive sulforaphane from 15-30 weeks; in Phase 3, children will
      receive no treatment for 6 weeks. Study visits will take place at screening, 7, 15, 22, 30
      and 36 weeks, when the Ohio Autism Clinical Clinical Impressions Scale - Severity and
      Improvement (OACIS-S and OACIS-I), Aberrant Behavior Checklist (ABC) and Social
      Responsiveness Scale (SRS) will be recorded.

      The children will be monitored with physical examinations and for toxicity with clinical
      laboratory studies and examine possible biomarkers: Nrf2, oxidative stress and mitochondrial
      function, mTOR pathway and cytokine expression.

      In addition, prior to the main clinical trial, a pilot study will be performed in 10 children
      with ASD, 6-12 years of age, who will receive sulforaphane, 2.2 micromoles/kg daily for 14
      days. Blood and urine samples before and at the end of treatment will be collected, in order
      to measure several parameters that are likely to demonstrate expected effects of
      sulforaphane, to standardize the assays and procedures, and to determine the most effective
      measures.
    

Intervention name(s): Sulforaphane; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): See under active arm description; See under placebo arm description
Intervention MeSH terms: Sulforaphane
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment