Abstract
Objective: Study the safety, clinical effects and mechanisms of action of sulforaphane in ASD.
Background: Direct treatment of underlying mechanisms in ASD is limited. The “fever effect” in ASD, in which febrile illness temporarily ameliorates disordered behavior, may offer a clinical clue. Fever stimulates heat shock proteins (HSP) and cellular stress responses, leading to improved synaptic function and long-range connectivity. Expression of gene transcription by NFE2L2 (Nrf2), which is reduced in ASD, also increases during fever. Sulforaphane (SF), an isothiocyanate obtained from broccoli sprouts, induces HSP and Nrf2 as well as “cell-protective” responses that may benefit ASD through common cellular mechanisms underlying heterogeneous phenotypes.
Design/Methods: This is a randomized, double-blind, placebo-controlled phase-2 clinical trial to test the safety and efficacy of oral SF in 50 children (age 3–12 years) with ASD. Treatment period is 30 weeks, with study-visits at screening, 7, 15, 22, 30 and 36 weeks. The first 15 weeks are double-blind, 1:1 placebo-controlled, and the second 15 weeks are open-label with all participants receiving SF. Ohio Autism Clinical Global Impressions Scale – Severity and Improvement (OACIS-S and I), Aberrant Behavior Checklist (ABC) and Social Responsiveness Scale (SRS) are administered at each study visit. Samples are collected for clinical and research lab studies at each visit.
Results: To date, we have enrolled 46 participants in the study; 24 participants have completed the trial, and 22 are actively enrolled. A preliminary analysis of the OACIS-I showed that 26% participants were much/very much improved at 7 weeks, 38% at 15 weeks, 64% at 22 weeks, and 64% at 30 weeks. Most common adverse events so far are insomnia (17%), flatulence (15%) and constipation (13%). Enrollment is expected to be complete in November, 2017, and full results after July, 2018.
Conclusions: Our preliminary results show that sulforaphane appears to be safe and effective in children with ASD.
Study Supported by: United States Department of Defense
Disclosure: Dr. Zimmerman has nothing to disclose. Dr. Diggins has nothing to disclose. Dr. Connors has nothing to disclose. Dr. Singh has nothing to disclose.
Disputes & Debates: Rapid online correspondence
REQUIREMENTS
If you are uploading a letter concerning an article:
You must have updated your disclosures within six months: http://submit.neurology.org
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.