A 12-weeks Study to Evaluate Sulforaphane in Treatment of Autism Spectrum Disorder

Overview

In this proposed study, the investigators will evaluate the the efficacy, safety and related mechanism of sulforaphane in treatment of autism spectrum disorder (ASD). The study will recruit 120 ASD patients, then these patients will be randomized to sulforaphane group or placebo group (60 patients per arm) for 12 weeks clinic trial. Clinical efficacy and safety assessment will be done at screen/baseline, 4 week, 8 week and 12 week. The specific aims are to compare sulforaphane versus placebo on: 1) clinical core symptoms; 2) other behavioral problems and adaptive behaviors. Biological samples also will be collected, and stored to research related mechanisms.

Full Title of Study: “A 12-weeks, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety and Related Mechanism of Sulforaphane in Treatment of Autism Spectrum Disorder”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: July 2019

Detailed Description

In this proposed study, the investigators will evaluate the the efficacy, safety and related mechanism of sulforaphane in treatment of autism spectrum disorder (ASD). The study will recruit 120 ASD patients, then these patients will be randomized to sulforaphane group or placebo group (60 patients per arm) for 12 weeks clinic trial. Clinical efficacy and safety assessment will be done at screen/baseline, 4 week, 8 week and 12 week. The specific aims are to compare sulforaphane versus placebo on: 1) clinical core symptoms; 2) other behavioral problems and adaptive behaviors. The investigators hypothesize that (1) sulforaphane is superior to placebo in the treatment of clinical symptoms in patients with ASD, measured by the Social Responsiveness Scale, Aberrant Behavior Checklist, Repetitive Behavior Scale - Revised and Ohio State University Autism Clinical Global Impression; (2) sulforaphane is superior to placebo in the treatment of other behavioral problems and adaptive behaviors patients with ASD, measured by Achenbach's Child Behavior Checklist and Adaptive Behavior Assessment System, Second Edition; and (3) Biological samples will be collected, and stored so that the hypothesis sulforaphane may alter oxidative stress indexes or inflammatory biomarkers, and influence histone deacetylase inhibitor mechanism or inflammatory mechanism et al that may be significantly correlated with clinical improvement.

Interventions

  • Dietary Supplement: Sulforaphane
    • Sulforaphane (SFN) is a compound within the isothiocyanate group of organosulfur compounds. It is obtained from cruciferous vegetables such as broccoli, Brussels sprouts or cabbages.
  • Other: Placebo
    • Placebo tablet is composed of starch.

Arms, Groups and Cohorts

  • Experimental: Sulforaphane group
    • The patients will take sulforaphane for 12 weeks.
  • Placebo Comparator: Placebo group
    • The patients will take placebo for 12 weeks.

Clinical Trial Outcome Measures

Primary Measures

  • The change of social impairments of children with autism spectrum disorder
    • Time Frame: At baseline, 4 week, 8 week and 12 week/endpoint
    • Social impairments are measured by Social Responsiveness Scale

Secondary Measures

  • The change of rigid interests and behaviors of children with autism spectrum disorder
    • Time Frame: At baseline, 4 week, 8 week and 12 week/endpoint
    • Rigid interests and behaviors are measured by Repetitive Behavior Scale – Revised
  • The change of clinical symptoms of children with autism spectrum
    • Time Frame: At baseline, 4 week, 8 week and 12 week/endpoint
    • Clinical symptoms are measured by Aberrant Behavior Checklist
  • The change of other behavioral problems of children with autism spectrum
    • Time Frame: At baseline, 4 week, 8 week and 12 week/endpoint
    • Other behavioral problems are measured by Achenbach’s Child Behavior Checklist
  • The change of adaptive behaviors of children with autism spectrum
    • Time Frame: At baseline, 4 week, 8 week and 12 week/endpoint
    • Adaptive behaviors are measured by Adaptive Behavior Assessment System, Second Edition
  • The change of clinical general impression of children with autism spectrum
    • Time Frame: At baseline, 4 week, 8 week and 12 week/endpoint
    • Clinical general impression is measured by Ohio State University Autism Clinical Global Impression
  • The change of heart rate as measured by stopwatch
    • Time Frame: At baseline and 12 week/endpoint
  • The change of weight as measured by weighing-machine
    • Time Frame: At baseline and 12 week/endpoint
  • The change of height as measured by Height measurement tools
    • Time Frame: At baseline and 12 week/endpoint
  • The change of blood routine test as tested by clinical laboratory
    • Time Frame: At baseline and 12 week/endpoint
  • The change of fasting blood-glucose as tested by clinical laboratory
    • Time Frame: At baseline and 12 week/endpoint
  • The change of blood lipid as tested by clinical laboratory
    • Time Frame: At baseline and 12 week/endpoint
  • The change of liver function as tested by clinical laboratory
    • Time Frame: At baseline and 12 week/endpoint
  • The change of kidney function as tested by clinical laboratory
    • Time Frame: At baseline and 12 week/endpoint
  • The change of thyroid function as tested by clinical laboratory
    • Time Frame: At baseline and 12 week/endpoint
  • The change of HBV test as tested by clinical laboratory
    • Time Frame: At baseline and 12 week/endpoint
  • The change of helicobacter pylori test as tested by clinical laboratory
    • Time Frame: At baseline and 12 week/endpoint
  • The change of urine routine test as tested by clinical laboratory
    • Time Frame: At baseline and 12 week/endpoint
  • Number of participants with treatment-related adverse events as assessed by Systematic Assessment for Treatment Emergent Effects
    • Time Frame: At 4 week, 8 week and 12 week/endpoint

Participating in This Clinical Trial

Inclusion Criteria

1. Aged 3 to 15 years. 2. Meet DSM-V diagnostic criteria for autism spectrum disorder, and been checked with Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS). Exclusion Criteria:

1. With severe physical disease (i.e. congenital heart disease, thyroid disease, diseases with severe abnormality of liver or kidney function, diseases with abnormality vision or hearing et al.) 2. With severe central nervous system disease (i.e. epilepsy et al). 3. With other specific genetic syndromes (i.e. Fragile-X syndrome, Down's syndrome et al.)

Gender Eligibility: All

Minimum Age: 3 Years

Maximum Age: 15 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Central South University
  • Collaborator
    • Davis family funding
  • Provider of Information About this Clinical Study
    • Principal Investigator: Jian-Jun Ou, Assistant researcher – Central South University
  • Overall Official(s)
    • Jingping Zhao, M.D., Ph. D., Study Chair, Central South University
    • Jianjun Ou, M.D., Ph. D., Study Director, Central South University
    • Hua Jin, M.D., Ph. D., Study Director, Department of Psychiatry, University of California
    • Fengyu Zhang, Ph.D., Principal Investigator, Global Clinical and Translational Research Institute
    • Daomeng Cheng, M.D., Principal Investigator, Guangzhou Huiai Hospital
    • Renrong Wu, M.D.,Ph.D, Principal Investigator, Central South University
    • John M Davis, M.D.,Ph.D, Study Director, Department of Psychiatry, University of Illinoisat at Chicago

References

Foley AG, Cassidy AW, Regan CM. Pentyl-4-yn-VPA, a histone deacetylase inhibitor, ameliorates deficits in social behavior and cognition in a rodent model of autism spectrum disorders. Eur J Pharmacol. 2014 Mar 15;727:80-6. doi: 10.1016/j.ejphar.2014.01.050. Epub 2014 Jan 31.

Houghton CA, Fassett RG, Coombes JS. Sulforaphane: translational research from laboratory bench to clinic. Nutr Rev. 2013 Nov;71(11):709-26. doi: 10.1111/nure.12060. Epub 2013 Oct 22.

Moldrich RX, Leanage G, She D, Dolan-Evans E, Nelson M, Reza N, Reutens DC. Inhibition of histone deacetylase in utero causes sociability deficits in postnatal mice. Behav Brain Res. 2013 Nov 15;257:253-64. doi: 10.1016/j.bbr.2013.09.049. Epub 2013 Oct 5.

Foley AG, Gannon S, Rombach-Mullan N, Prendergast A, Barry C, Cassidy AW, Regan CM. Class I histone deacetylase inhibition ameliorates social cognition and cell adhesion molecule plasticity deficits in a rodent model of autism spectrum disorder. Neuropharmacology. 2012 Sep;63(4):750-60. doi: 10.1016/j.neuropharm.2012.05.042. Epub 2012 Jun 6.

Montes G, Halterman JS. Association of childhood autism spectrum disorders and loss of family income. Pediatrics. 2008 Apr;121(4):e821-6. doi: 10.1542/peds.2007-1594.

Montes G, Halterman JS. Child care problems and employment among families with preschool-aged children with autism in the United States. Pediatrics. 2008 Jul;122(1):e202-8. doi: 10.1542/peds.2007-3037.

Mugno D, Ruta L, D'Arrigo VG, Mazzone L. Impairment of quality of life in parents of children and adolescents with pervasive developmental disorder. Health Qual Life Outcomes. 2007 Apr 27;5:22. doi: 10.1186/1477-7525-5-22.

Myzak MC, Tong P, Dashwood WM, Dashwood RH, Ho E. Sulforaphane retards the growth of human PC-3 xenografts and inhibits HDAC activity in human subjects. Exp Biol Med (Maywood). 2007 Feb;232(2):227-34.

Ou JJ, Shi LJ, Xun GL, Chen C, Wu RR, Luo XR, Zhang FY, Zhao JP. Employment and financial burden of families with preschool children diagnosed with autism spectrum disorders in urban China: results from a descriptive study. BMC Psychiatry. 2015 Jan 22;15:3. doi: 10.1186/s12888-015-0382-4.

Rossignol DA, Frye RE. A review of research trends in physiological abnormalities in autism spectrum disorders: immune dysregulation, inflammation, oxidative stress, mitochondrial dysfunction and environmental toxicant exposures. Mol Psychiatry. 2012 Apr;17(4):389-401. doi: 10.1038/mp.2011.165. Epub 2011 Dec 6.

Schieve LA, Blumberg SJ, Rice C, Visser SN, Boyle C. The relationship between autism and parenting stress. Pediatrics. 2007 Feb;119 Suppl 1:S114-21. doi: 10.1542/peds.2006-2089Q.

Singh K, Connors SL, Macklin EA, Smith KD, Fahey JW, Talalay P, Zimmerman AW. Sulforaphane treatment of autism spectrum disorder (ASD). Proc Natl Acad Sci U S A. 2014 Oct 28;111(43):15550-5. doi: 10.1073/pnas.1416940111. Epub 2014 Oct 13.

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