Safety, effectiveness, and economic evaluation of an herbal medicine, Ukgansangajinpibanha granule, in children with autism spectrum disorder: a study protocol for a prospective, multicenter, randomized, double-blinded, placebo-controlled, parallel-group clinical trial

Sun Haeng Lee1, Sei One Shin2, Tae-Hun Kim3, Sang Min Kim1, Tae Hyun Yoon1, Sulgi Park1, Boram Lee1, Hye Jin Shin1, Jihong Lee1, Jin Yong Lee4, Gyu Tae Chang5
1Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea
2Department of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea
3Korean Medicine Clinical Trial Center, Kyung Hee University Korean Medicine Hospital, Kyung Hee University Medical Center, 23 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea
4Department of Pediatrics of Korean Medicine, Kyung Hee University Korean Medicine Hospital, Kyung Hee University Medical Center, 23 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea
5Department of Pediatrics of Korean Medicine, Kyung Hee University Hospital at Gangdong, 892 Dongnam-ro, Gangdong-gu, Seoul, 05278, Republic of Korea

Tóm tắt

Từ khóa


Tài liệu tham khảo

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Seoul: Hakjisa; 2015.

Fombonne E. Epidemiology of pervasive developmental disorders. Pediatr Res. 2009;65:591–8.

Christensen DL, Bilder DA, Zahorodny W, Pettygrove S, Durkin MS, Fitzgerald RT, et al. Prevalence and characteristics of autism spectrum disorder among 4-year-old children in the autism and developmental disabilities monitoring network. J Dev Behav Pediatrics. 2016;37:1–8.

Scottish Intercollegiate Guidelines Network (SIGN). Assessment, diagnosis and interventions for autism spectrum disorders. Edinburgh: SIGN; 2016.

Textbook Compiliation Committee. Pediatrics of Korean Medicine. revised edn. Seoul: Euisungdang; 2015.

Cho KH, Kim TH, Jin C, Lee JE, Kwon S. The literary trends of herbal prescription Ukgan-san and its application in modern traditional Korean medicine. J Korean Med. 2018;39:17–27.

Wake R, Miyaoka T, Furuya M, Hashioka S, Horiguchi J. Effects of Yokukansan, a Japanese Kampo Medicine for Symptoms Associated Autism Spectrum Disorder. CNS Neurol Disord Drug Targets. 2016;15:551–63.

Muneoka K, Kuwagata M, Ogawa T, Shioda S. Mother/offspring co-administration of the traditional herbal remedy yokukansan during the nursing period influences grooming and cerebellar serotonin levels in a rat model of neurodevelopmental disorders. Cerebellum. 2015;14:86–96.

Fujiwara H, Han Y, Ebihara K, Awale S, Araki R, Yabe T, et al. Daily administration of yokukansan and keishito prevents social isolation-induced behavioral abnormalities and down-regulation of phosphorylation of neuroplasticity-related signaling molecules in mice. BMC Complement Altern Med. 2017;17:195.

Sato R, Kato K, Yamada K, Akama F, Kimoto K, Kimoto K, et al. A case of irritability with autistic disorder in children and adolescents improved by Yokukansan. Psychiatr. 2002;20:693–8.

Wake R, Miyaoka T, Inagaki T, Furuya M, Ieda M, Liaury K, et al. Yokukansan (TJ-54) for irritability associated with pervasive developmental disorder in children and adolescents: a 12-week prospective, open-label study. J Child Adolesc Psychopharmacol. 2013;23:329–36.

Miyaoka T, Wake R, Furuya M, Liaury K, Ieda M, Kawakami K, et al. Yokukansan (TJ-54) for treatment of pervasive developmental disorder not otherwise specified and Asperger’s disorder: a 12-week prospective, open-label study. BMC Psychiatry. 2012;12:215.

Japanese Pediatric Oriental Medicine Association. Handbook of Kampo treatment for children. Tokyo: Japan Pediatric Medical Publishers; 2015.

KIPC DRUG INFO. [ http://www.health.kr/searchDrug/result_drug.asp?drug_cd=2014091600004 ]. Accessed 31 July 2018.

McElhanon BO, McCracken C, Karpen S, Sharp WG. Gastrointestinal symptoms in autism spectrum disorder: a meta-analysis. Pediatrics. 2014;133:872–83.

Lyra L, Rizzo LE, Sunahara CS, Pachito DV, Latorraca COC, et al. What do Cochrane systematic reviews say about interventions for autism spectrum disorders? Sao Paulo Med J. 2017;135:192–201.

Abo Almaali HMM, Gelewkhan A, Mahdi ZAA. Analysis of Evidence-Based Autism Symptoms Enhancement by Acupuncture. J Acupunct Meridian Stud. 2017;10:375–84.

Lee B, Lee J, Cheon JH, Sung HK, Cho SH, Chang GT. The Efficacy and Safety of Acupuncture for the Treatment of Children with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. Evid Based Complement Alternat Med. 2018;2018:1057539.

Liu C, Li T, Wang Z, Zhou R, Zhuang L. Scalp acupuncture treatment for children's autism spectrum disorders: A systematic review and meta-analysis. Medicine (Baltimore). 2019;98:e14880.

Shin MS, Kim YH. Standardization study for the Korean version of Childhood Autism Rating Scale: reliability, validity and cut-off score. Korean J Clin Psychol. 1998;17:1–15.

Krug DA, Arick J, Almond P. Behavior checklist for identifying severely handicapped individuals with high levels of autistic behavior. J Child Psychol Psychiatry. 1980;21:221–9.

Eaves RC, Williams TO. The reliability and construct validity of ratings for the autism behavior checklist. Psychol Sch. 2006;43:129–42.

Johnson CP, Myers SM, American Academy of Pediatrics Council on Children With Disabilities. Identification and evaluation of children with autism spectrum disorders. Am Acad Pediatrics Counc Children Disabil. 2007;120:1183–215.

Yousefi N, Dadgar H, Mohammadi MR, Jalilevand N, Keyhani MR, Mehri A. The Validity and Reliability of Autism Behavior Checklist in Iran. Iran J Psychiatry. 2015;10:144–9.

Aman MG, Singh NN, Stewart AW, Field CJ. Psychometric characteristics of the aberrant behavior checklist. Am J Ment Defic. 1985;89:492–502.

Scahill L, Hallett V, Aman MG, McDougle CJ, Eugene Arnold L, McCracken JT, et al. Brief Report: social disability in autism spectrum disorder: results from Research Units on Pediatric Psychopharmacology (RUPP) Autism Network trials. J Autism Dev Disord. 2013;43:739–46.

Aman MG, Singh NN, Turbott SH. Reliability of the Aberrant Behavior Checklist and the effect of variations in instructions. Am J Ment Defic. 1987;92:237–40.

Kim SG, Kim OG. Social Maturity Scale Protocol. Seoul: Jungang Aptitude Laboratory; 1995.

Raat H, Bonsel GJ, Essink-Bot ML, Landgraf JM, Gemke RJ. Reliability and validity of comprehensive health status measures in children: The Child Health Questionnaire in relation to the Health Utilities Index. J Clin Epidemiol. 2002;55:67–76.

Ravens-Sieberer U, Wille N, Badia X, Bonsel G, Burström K, et al. Feasibility, reliability, and validity of the EQ-5D-Y: results from a multinational study. Qual Life Res. 2010;19:887–97.

Abidin RR, Jung GM, Lee GS, Park JA. Guide to Korean Parenting Stress Index. Seoul: Insight of Psychology; 2008.

Zhou NY, Li YC, Jiang XY. Clinical Observation of Supplemented Lizhong Decoction in Treating Children Autism. J New Chinese Med. 2015;47(6):200–2.

Sun YB, Song HJ, Feng TZ, Yuan Y, Zhao NX. Comprehensive treatment of 60 cases of childhood autism. Liaoning J Tradit Chin Med. 2016;43:2105–8.

Bang M, Lee SH, Cho SH, Yu SA, Kim K, Lu HY, et al. Herbal Medicine Treatment for Children with Autism Spectrum Disorder: A Systematic Review. Evid Based Complement Alternat Med. 2017;2017:8614680.

Christensen DL, Baio J, Van Naarden Braun K, Bilder D, Charles J, Constantino JN, et al. Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 8 Years--Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2012. MMWR Surveill Summ. 2016;65:1–23.

Shin SH. Understanding of high-functioning autism spectrum disorder. In: 2019 Spring Conference and Workshop. Seoul: Korean Association for Persons with Autism, Korean Academy for Autism Spectrim Disorder; 2019.

Tamano H, Yusuke E, Ide K, Takeda A. Influences of yokukansankachimpihange on aggressive behavior of zinc-deficient mice and actions of the ingredients on excessive neural exocytosis in the hippocampus of zinc-deficient rats. Exp Anim. 2016;65:353–61.

Ito A, Shin N, Tsuchida T, Okubo T, Norimoto H. Antianxiety-like effects of Chimpi (dried citrus peels) in the elevated open-platform test. Molecules. 2013;18:10014–23.

Murayama C, Watanabe S, Nakamura M, Norimoto H. Inhibitory Activity of Yokukansankachimpihange against Nerve Growth Factor-Induced Neurite Growth in Cultured Rat Dorsal Root Ganglion Neurons. Molecules. 2015;20:14959–69.

Aizawa R, Kanbayashi T, Saito Y, Ogawa Y, Sugiyama T, Kitajima T, et al. Effects of Yoku-kan-san-ka-chimpi-hange on the sleep of normal healthy adult subjects. Psychiatry Clin Neurosci. 2002;56:303–4.

Shin HJ, Lee B, Lee J, Chang GT. A clinical study of treating autism spectrum disorder in childhood. J Pediatr Korean Med. 2017;31:49–60.