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

Autism Spectrum Disorder Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02879110
• Other study ID #: ASD201512
• Status: Completed
• Phase: N/A
• Start date: August 2016
• Est. completion date: July 2019

Study information

• Verified date: July 2019
• Source: Central South University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 110
• Est. completion date: July 2019
• Est. primary completion date: July 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 15 Years

Eligibility

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.)

Related Conditions & MeSH terms

• Autism Spectrum Disorder
• Autistic Disorder
• Child Development Disorders, Pervasive
• Disease

Intervention

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.

Locations

Country	Name	City	State
China	The second Xiangya hospital of central south university	Changsha	Hunan
China	Guangzhou Huiai Hospital	Guangzhou	Guangdong

Sponsors (4)

Lead Sponsor	Collaborator
Central South University	Davis family funding, University of California, University of Illinois at Chicago

Country where clinical trial is conducted

China, 

References & Publications (12)

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	The change of Oxidative stress indexes as tested by Oxidative stress indexes detection kit		At baseline and 12 week/endpoint
Other	The change of Epigenetics indicators as tested by Epigenetics indicators		At baseline and 12 week/endpoint
Other	The change of Cytokines & Chemokines as tested by Cytokines & Chemokines detection kit		At baseline and 12 week/endpoint
Other	The change of Metabolites as tested by Metabolites detection kit		At baseline and 12 week/endpoint
Other	The change of RNA expression as tested by RNA expression detection kit		At baseline and 12 week/endpoint
Other	The change of intestinal microflora as tested by Metagenomic technique		At baseline and 12 week/endpoint
Primary	The change of social impairments of children with autism spectrum disorder	Social impairments are measured by Social Responsiveness Scale	At baseline, 4 week, 8 week and 12 week/endpoint
Secondary	The change of rigid interests and behaviors of children with autism spectrum disorder	Rigid interests and behaviors are measured by Repetitive Behavior Scale - Revised	At baseline, 4 week, 8 week and 12 week/endpoint
Secondary	The change of clinical symptoms of children with autism spectrum	Clinical symptoms are measured by Aberrant Behavior Checklist	At baseline, 4 week, 8 week and 12 week/endpoint
Secondary	The change of other behavioral problems of children with autism spectrum	Other behavioral problems are measured by Achenbach's Child Behavior Checklist	At baseline, 4 week, 8 week and 12 week/endpoint
Secondary	The change of adaptive behaviors of children with autism spectrum	Adaptive behaviors are measured by Adaptive Behavior Assessment System, Second Edition	At baseline, 4 week, 8 week and 12 week/endpoint
Secondary	The change of clinical general impression of children with autism spectrum	Clinical general impression is measured by Ohio State University Autism Clinical Global Impression	At baseline, 4 week, 8 week and 12 week/endpoint
Secondary	The change of heart rate as measured by stopwatch		At baseline and 12 week/endpoint
Secondary	The change of weight as measured by weighing-machine		At baseline and 12 week/endpoint
Secondary	The change of height as measured by Height measurement tools		At baseline and 12 week/endpoint
Secondary	The change of blood routine test as tested by clinical laboratory		At baseline and 12 week/endpoint
Secondary	The change of fasting blood-glucose as tested by clinical laboratory		At baseline and 12 week/endpoint
Secondary	The change of blood lipid as tested by clinical laboratory		At baseline and 12 week/endpoint
Secondary	The change of liver function as tested by clinical laboratory		At baseline and 12 week/endpoint
Secondary	The change of kidney function as tested by clinical laboratory		At baseline and 12 week/endpoint
Secondary	The change of thyroid function as tested by clinical laboratory		At baseline and 12 week/endpoint
Secondary	The change of HBV test as tested by clinical laboratory		At baseline and 12 week/endpoint
Secondary	The change of helicobacter pylori test as tested by clinical laboratory		At baseline and 12 week/endpoint
Secondary	The change of urine routine test as tested by clinical laboratory		At baseline and 12 week/endpoint
Secondary	Number of participants with treatment-related adverse events as assessed by Systematic Assessment for Treatment Emergent Effects		At 4 week, 8 week and 12 week/endpoint