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: A UGSJB granule with acupuncture, twice daily (n = 120) 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) Electronic supplementary material The online version of this article (10.1186/s13063-019-3537-7) contains supplementary material, which is available to authorized users.

Dietary nutrients that potentially mitigate autism spectrum disorder and dietary recommendations for children and pregnant women

“…As adjunct therapies, acupuncture and moxibustion have been clinically used to improve the language and social ability of children with ASD (Surapaty et al., 2020). These techniques have few side effects and can be combined with Chinese herbal medicine for synergistic treatment (Lee et al., 2019). rTMS is the most widely used intervention, as it significantly improves the quality of life, social deficits, and verbal communication of children with ASD.…”

Research status and prospects of acupuncture for autism spectrum disorders

“…Sufficient sample size can test the feasibility of clinical application of treatment method ( 47 ). As shown in Table 1 , only one clinical trial had more than 100 participants, which may explain why there is not enough evidence to prove whether acupuncture is effective in the treatment of ASD in the past 15 years ( 6 ). The small number of participants in other studies will increase the risk of failing to show the significant treatment benefits of acupuncture ( 47 ).…”

“…Understandably, this depends on the actual situation of the patients included in the study. However, the golden treatment time for ASD is known to be between the ages of 2 and 6 years ( 6 ). Whether adolescent patients will have heterogeneity of ASD due to exposure to more external environmental factors remains to be further discussed ( 53 ).…”

“…In the study by Surapaty et al ( 38 ), the patients in the experimental group experienced sensory-occupational integrative therapy with the patients of control group before receiving acupuncture, and their speech ability and social interaction were finally found to be more improved than those in the control group. Lee et al ( 6 ) found that herbal medicine combined with acupuncture is safer and more effective in the treatment of ASD than placebo combined with acupuncture. Zhang et al ( 41 ) implemented TEAS in ASD patients who received rehabilitation training and found that TEAS was more effective for autistic children with a passive and aloof social interaction style than simple rehabilitation training.…”

“…Although risperidone and aripiprazole can improve patients’ agitation and irritability, they are often accompanied by adverse effects such as weight gain, nausea, sedation, and hyperglycemia ( 2 ). In addition, methylphenidate, atomoxetine, and guanfacine have been used to improve attention-deficit and hyperactivity disorder, but can cause adverse effects such as sleep disruption, loss of appetite, nausea, irritability, fatigue, sedation, and hypotension ( 2 , 6 ). In addition to pharmacological therapy, behavioral and educational intervention (BEI) has also been used in the treatment of ASD, but most high-quality BEI need 20–40 h of treatment per week, and it takes a long time to show benefits ( 7 , 8 ).…”