Correlating single nucleotide polymorphisms in vitamin D metabolism-related genes to autism susceptibility and vitamin D treatment: study protocol of a non-randomized parallel-cohort controlled trial

Background: Vitamin D plays a unique role in promoting embryonic and neural development, cerebral immunological regulation, and influencing neural differentiation and gene regulation. Vitamin D deficiency may be one of the environmental risk factors for autism spectrum disorder. This trial has two purposes: (1) correlating single nucleotide polymorphisms of vitamin D metabolism-related key enzymes to autism susceptibility; and (2) investigating the therapeutic effect of exogenous vitamin D on autism spectrum disorder. Methods/Design: A non-randomized parallel-cohort controlled trial. Sixty children with autism spectrum disorder who receive treatment at the Department of Pediatric Neurological Rehabilitation, First Hospital, Jilin University, China, are included. Sixty healthy controls are also recruited from those undergoing a physical examination. For the first purpose, primary outcomes include vitamin D metabolism and single nucleotide polymorphisms of related genes. Vitamin D level in peripheral blood is the secondary outcome. For the second purpose, 60 children with autism spectrum disorder are treated with exogenous vitamin D supplementation. Prior to and 1 month after exogenous vitamin D supplementation, primary outcomes are evaluated, including the Childhood Autism Rating Scale (CARS) score, Autism Behavior Checklist (ABC) score, the Gesell Developmental Schedules (GDS) score, Clinical Global Impression Scale-(CGI) for severity of illness (SI), global improvement (GI), and efficacy index (EI) scores. Again, vitamin D levels in peripheral blood are evaluated as the secondary outcome. Discussion: This trial is sufficiently powered to provide scientific evidence for the genetic and pathological mechanism of autism spectrum disorder in children that lack vitamin D. Trial registration: Chinese Clinical Trial Registry (http://www.chictr.org.cn/index.aspx) identifier: ChiCTR-TRC-14004499; registered on 30 November 2013. Ethical issues: This trial was approved by the Medical Ethics Committee, First Hospital of Jilin University, China (approval No. 2013-192). The trial protocol will be performed in accordance with the Declaration of Helsinki.