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

Abstract

Background: Autism spectrum disorder (ASD) is characterized by continuous impairment in communication and social interaction and by limited and repetitive behaviors, interests, or activities. Behavioral, educational, and pharmaceutical interventions have been shown to reduce behavioral disabilities, improve verbal/non-verbal communication, and help patients acquire self-reliance skills. However, there has been a lack of systematic verification and consensus regarding the treatment of the core symptoms of ASD because of its unclear etiology. Ukgansangajinpibanha (UGSJB), a legitimately prescribed herbal medicine for nervousness, insomnia, night crying, and malnutrition in South Korea and Japan, has been used for angry, sensitive, nervous, and unsettled children with ASD.

Methods/design: This trial is a prospective, multicenter, randomized, double-blinded, placebo-controlled, parallel-group, clinical trial. The 4- to 6-year-old children with ASD will be randomly assigned to following groups: 1. A UGSJB granule with acupuncture, twice daily (n = 120) 2. A placebo group with acupuncture, twice daily (n = 120). The following outcome measures will be used: behavior by the Childhood Autism Rating Scale, Autism Behavior Checklist, and Aberrant Behavior Checklist; social maturity by the Social Maturity Scale; quality of life by the Child Health Questionnaire and EuroQoL Five-dimension Five-level Youth; and parental stress by the Parenting Stress Index at baseline and at 6, 12, and 24 weeks after the beginning of treatment. In addition, to evaluate safety, we will investigate the adverse reactions that may be caused by UGSJB granule. Finally, we will make an economic evaluation of UGSJB for the treatment of ASD.

Discussion: We prepared a well-designed clinical trial to investigate the safety and effectiveness of UGSJB on ASD symptoms compared with placebo treatment. The results from this study will provide clinical evidence on the safety, effectiveness, and economic value of UGSJB combined with acupuncture in children with ASD.

Trial registration: Clinical Research Information Service: KCT0003007 (registered on April 5, 2018).

Keywords: Acupuncture; Autism spectrum disorder; Herbal medicine; Randomized controlled trial; Ukgansangajinpibanha.

Fig. 1

Schematic chart of the process of the clinical trial. Abbreviations: ABC¹ Autism Behavior Checklist, ABC² Aberrant Behavior Checklist, ACER Average cost-effectiveness ratio, ACUR Average cost-utility ratio, AE Adverse event, ANCOVA Analysis of covariance, ASD Autism spectrum disorder, CARS Childhood Autism Rating Scale, CBA Cost-benefit analysis, CEA Cost-effectiveness analysis, CHQ-PF28 Child Health Questionnaire-Parent Report Form 28, CUA Cost-utility analysis, EQ-5D-Y EuroQoL Five-dimension Five-level Youth, FAS Full analysis set, ICER Incremental cost-effectiveness ratio, IRB Institutional review board, K-CTC Korean Medicine Clinical Trial Center, K-PSI-SF Korean Parenting Stress Index Short Form, PDD Pervasive developmental disorder, PPS Per protocol set, PSI Parenting Stress Index, RCT Randomized controlled trial, SAS Safety Assessment Set, SMS Social Maturity Scale, TCM Traditional Chinese Medicine,UGSJB Ukgansangajinpibanha

Fig. 2

Schedule of enrolment, interventions, and assessments. Abbreviations: ABC¹ Autism Behavior Checklist, ABC² Aberrant Behavior Checklist, CARS Childhood Autism Rating Scale, CHQ-PF28 Child Health Questionnaire-Parent Report Form 28, EQ-5D-Y EuroQoL Five-dimension Five-level Youth, K-PSI-SF Korean Parenting Stress Index Short Form, SMS Social Maturity Scale, UGSJB Ukgansangajinpibanha