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

• ClinicalTrials.gov Identifier: NCT02879110
• Recruitment Status: Completed
• First Posted: August 25, 2016
• Last Update Posted: July 30, 2019
• Sponsor: Central South University
• Collaborators: Davis family funding; University of California; University of Illinois at Chicago
• Information provided by (Responsible Party): Jian-Jun Ou, Central South University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Autism Spectrum Disorder	Dietary Supplement: Sulforaphane; Other: Placebo	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 110 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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 Start Date: August 2016
• Actual Primary Completion Date: July 2019
• Actual Study Completion Date: July 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Sulforaphane group; The patients will take sulforaphane for 12 weeks.	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 Name: 85313323
Placebo Comparator: Placebo group; The patients will take placebo for 12 weeks.	Other: Placebo; Placebo tablet is composed of starch.; Other Name: Starch tablet

Outcome Measures

Primary Outcome Measures :

1. 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 Outcome Measures :

1. 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
2. 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
3. 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
4. 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
5. 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
6. The change of heart rate as measured by stopwatch [ Time Frame: At baseline and 12 week/endpoint ]
7. The change of weight as measured by weighing-machine [ Time Frame: At baseline and 12 week/endpoint ]
8. The change of height as measured by Height measurement tools [ Time Frame: At baseline and 12 week/endpoint ]
9. The change of blood routine test as tested by clinical laboratory [ Time Frame: At baseline and 12 week/endpoint ]
10. The change of fasting blood-glucose as tested by clinical laboratory [ Time Frame: At baseline and 12 week/endpoint ]
11. The change of blood lipid as tested by clinical laboratory [ Time Frame: At baseline and 12 week/endpoint ]
12. The change of liver function as tested by clinical laboratory [ Time Frame: At baseline and 12 week/endpoint ]
13. The change of kidney function as tested by clinical laboratory [ Time Frame: At baseline and 12 week/endpoint ]
14. The change of thyroid function as tested by clinical laboratory [ Time Frame: At baseline and 12 week/endpoint ]
15. The change of HBV test as tested by clinical laboratory [ Time Frame: At baseline and 12 week/endpoint ]
16. The change of helicobacter pylori test as tested by clinical laboratory [ Time Frame: At baseline and 12 week/endpoint ]
17. The change of urine routine test as tested by clinical laboratory [ Time Frame: At baseline and 12 week/endpoint ]
18. 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 ]

Other Outcome Measures:

1. The change of Oxidative stress indexes as tested by Oxidative stress indexes detection kit [ Time Frame: At baseline and 12 week/endpoint ]
2. The change of Epigenetics indicators as tested by Epigenetics indicators [ Time Frame: At baseline and 12 week/endpoint ]
3. The change of Cytokines & Chemokines as tested by Cytokines & Chemokines detection kit [ Time Frame: At baseline and 12 week/endpoint ]
4. The change of Metabolites as tested by Metabolites detection kit [ Time Frame: At baseline and 12 week/endpoint ]
5. The change of RNA expression as tested by RNA expression detection kit [ Time Frame: At baseline and 12 week/endpoint ]
6. The change of intestinal microflora as tested by Metagenomic technique [ Time Frame: At baseline and 12 week/endpoint ]

Eligibility Criteria

• Ages Eligible for Study: 3 Years to 15 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.)

Contacts and Locations

Locations

China, Guangdong

Guangzhou Huiai Hospital

Guangzhou, Guangdong, China, 510000

China, Hunan

The second Xiangya hospital of central south university

Changsha, Hunan, China, 410001

Sponsors and Collaborators

Central South University

Davis family funding

University of California

University of Illinois at Chicago

Investigators

• Study Chair: Jingping Zhao, M.D., Ph. D.; Central South University
• Study Director: Jianjun Ou, M.D., Ph. D.; Central South University
• Study Director: Hua Jin, M.D., Ph. D.; Department of Psychiatry, University of California
• Principal Investigator: Fengyu Zhang, Ph.D.; Global Clinical and Translational Research Institute
• Principal Investigator: Daomeng Cheng, M.D.; Guangzhou Huiai Hospital
• Principal Investigator: Renrong Wu, M.D.,Ph.D; Central South University
• Study Director: John M Davis, M.D.,Ph.D; Department of Psychiatry, University of Illinoisat at Chicago

More Information

Publications:

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.

• Responsible Party: Jian-Jun Ou, Assistant researcher, Central South University
• ClinicalTrials.gov Identifier: NCT02879110
• Other Study ID Numbers: ASD201512
• First Posted: August 25, 2016
• Last Update Posted: July 30, 2019
• Last Verified: July 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Jian-Jun Ou, Central South University:

Sulforaphane; clinic trial; Autism Spectrum Disorder; Efficacy; Safety; Mechanism

Additional relevant MeSH terms:

Disease; Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Pathologic Processes; Neurodevelopmental Disorders; Mental Disorders; Sulforaphane; Anticarcinogenic Agents; Protective Agents; Physiological Effects of Drugs; Antineoplastic Agents