Clinical trial NCT05980520: Study on the Treatment of Taurine in Children With Autism
Official title: Taurine Supplementation Improves Core Symptoms in Children With Autism Spectrum Disorders: an Exploratory Randomized, Double-blinded, Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Autism Spectrum Disorder
Keywords: autism spectrum disorders
children
taurine
Lead sponsor: Guizhou Provincial People's Hospital
Sponsor class: OTHER
First posted: 2023-08-08
Enrollment: 64
Sex: ALL
Minimum age (years): 30
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In the treatment of autism spectrum disorders (ASD), medication is only an adjunct, and the main treatment modalities are education and behavioral therapy. People with autism incur huge medical and educational costs, which puts a great financial burden on families.Taurine is one of the abundant amino acids in tissues and organs, and plays a variety of physiological and pharmacological functions in nervous, cardiovascular, renal, endocrine and immune systems. A large number of studies have shown that taurine can improve cognitive function impairment under various physiological or pathological conditions through a variety of mechanisms, taurine can increase the abundance of beneficial bacteria in the intestine, inhibit the growth of harmful bacteria, and have a positive effect on intestinal homeostasis. This study intends to analyze the effect of taurine supplementation on ASD, and explore the possible mechanism by detecting intestinal symptoms, intestinal flora, markers of oxidative stress and clinical symptoms of ASD.

Detailed description: Autism spectrum disorders (ASD) are the most common disabling disorders in childhood and are characterized by social difficulties, stereotyped behavior, narrow interests and paresthesia. In recent years, the prevalence of ASD has been increasing year by year, and the latest epidemiology in the United States shows that the prevalence of ASD is 1/44. The previous multi-center epidemiological survey of ASD in children in China showed that the prevalence of ASD in children aged 6-12 in China was about 0.7%, and the lifetime medical and non-medical expenses of ASD patients ranged from $1.4 million to $2.4 million. The survey showed that the disease burden of ASD in children aged 0-6 in Guizhou Province was between 60,000 and 80,000 yuan/year/person. ASD has become a major public health problem affecting children's health due to its high prevalence rate, disability rate and heavy disease burden, which has brought huge economic and social burden to families and society of children with ASD. At present, ASD has been listed as the leading disabling disease among mental diseases, bringing serious burden to families and society, and ASD has become a major public health problem affecting children's health.

At present, there are no specific drugs to improve the core symptoms of ASD, and education and behavioral therapy are mainly focused on early intervention to obtain the best results. Although effective behavioral interventions can significantly improve the core symptoms of children with ASD, a significant proportion of children with ASD still have residual functional disabilities. Therefore, the research and development of new treatment methods for children with ASD has become a hot and difficult problem. Children with ASD are prone to multiple nutrients due to poor eating habits, gastrointestinal symptoms and food allergies, and the addition of key nutrients is expected to become one of the important adjuvant treatments for children with ASD. The project team established a national children's ASD multi-center research cohort and built a children's ASD biobank under the financial support of the National Health Commission. A case-control (117:119) study using 1H-NMR metabolomics to detect urine samples of children with ASD showed lower taurine levels in the ASD group compared to the healthy control group. In recent years, taurine deficiency has been linked to neurological disorders or symptoms such as neurodegenerative diseases, stroke, epilepsy, and diabetic neuropathy. In addition, animal and clinical experiments have found that taurine supplementation has certain therapeutic effects on neurological diseases including Angelman behavior sign, fragile X behavior sign, sleep-wake disorder, stroke, attention deficit hyperactivity disorder, tic disorder, and taurine supplementation can improve anxiety symptoms and cognitive ability of mice. In previous animal intervention experiment, taurine supplementation on the basis of VPA autism model in rats during pregnancy was found to improve ASD-like behavior in offspring. However, there is a lack of population-based evidence in children with ASD.

Taurine is widely distributed in brain, spinal cord, heart, muscle cells and retina, and is one of the more abundant amino acids in almost all tissues and organs. A large number of studies have shown that taurine can protect a variety of tissues and organs from oxidative stress damage. Taurine can also ameliorate cognitive impairment in a variety of physiological and pathological conditions through a variety of mechanisms, including reducing neuroinflammation, up-regulating Nrf2 expression and antioxidant capacity, activating Akt/CREB/PGC1α signaling pathway to further enhance mitochondrial biosynthesis, synaptic function, and reducing oxidative stress. A large number of studies have shown that compared with healthy controls, the blood levels of oxidative stress markers in children with ASD are reduced or increased to varying degrees, and are thought to be related to the formation of stereotypical behaviors of ASD. Whether taurine can improve the core symptoms of ASD by reducing oxidative stress damage remains unclear, and human studies are needed to further clarify the mechanism of action and verify the findings of animal experiments.

In summary, taurine deficiency is closely related to the onset of neurodevelopmental disorders, and dietary supplementation may have a certain therapeutic effect. This study is based on this starting point to propose the basis of project. This study intends to conduct an exploratory randomized, double-blind controlled trial to compare and analyze the effect of taurine supplementation on the improvement of core symptoms in ASD children who were treated with routine behavioral rehabilitation combined with taurine supplement (experimental group) and behavioral rehabilitation combined with placebo (control group) for 3 months and continued follow-up for 12 months. The possible mechanism of action was investigated by detecting intestinal symptoms, intestinal flora, markers of oxidative stress and clinical symptoms of ASD. The aim of this study is to explore an effective and reliable adjuvant therapy for children with ASD. To investigate the curative effect of taurine supplementation on the core symptoms of children with ASD spectrum disorder. To observe the incidence of adverse reactions of taurine supplementation, evaluate the clinical application value of taurine supplementation, and provide theoretical support for further tests.

Eligibility criteria: Inclusion Criteria:

* Aged 2.5-18 years at enrollment.
* Meet the diagnosis criteria of ASD by the diagnostic and statistical manual of mental disorders(DSM-5).

Exclusion Criteria:

* Rett behavioral sign, cerebral palsy, other congenital diseases, associated with other inherited metabolic behavioral signs, epilepsy.
* Children who have had an acute or chronic infectious disease in the past 3 months.
* Children with abnormal liver and kidney function, chronic pulmonary heart disease.
* Children who have taken taurine supplements or medications in the past 3 months.
* Parents or patients refuse to participate in the study.
* The investigator determines that the subject is unable to comply with the study requirements.

Primary outcomes:
measure: Score of Autism Treatment Evaluation Checklist (ATEC)
timeFrame: From baseline till the 3th month.
Secondary outcomes:
measure: Score of Autism Treatment Evaluation Checklist (ATEC)
timeFrame: From baseline till the 1st,2rd,6th,9th,12th month.
measure: Childhood Autism Rating Scale(CARS)
timeFrame: At the 3rd,6th,9th,12th month from baseline.
measure: 6-item Gastrointestinal Severity Index(6-GSI)
timeFrame: At the1st,2rd,3rd,6th,9th,12th month from baseline.
measure: Autism Spectrum Rating Scales(ASRS)
timeFrame: At the1st,2rd,3rd,6th,9th,12th month from baseline.
measure: Social Responsiveness Scale(SRS)
timeFrame: At the1st,2rd,3rd,6th,9th,12th month from baseline.
measure: Identification and Management of Feeding Difficulties(IMFeD)
timeFrame: At the1st,2rd,3rd,6th,9th,12th month from baseline.
measure: Gesell Developmental Scale
timeFrame: At the 3rd,6th,9th,12th month from baseline.
measure: Children's Sleep Habits Questionnaire (CSHQ)
timeFrame: At the1st,2rd,3rd,6th,9th,12th month from baseline.
measure: The Wechsler intelligence scale (WISC) score
timeFrame: At the 3rd,6th,9th,12th month from baseline.
Other outcomes:
measure: Change of hemoglobin concentration in cortical metabolism
timeFrame: At the 3rd month from baseline.
measure: Change of taurine-related serum metabolites levels
timeFrame: At the 3rd month from baseline.
measure: Difference in proportions of Intestinal flora species(%)
timeFrame: At the 3rd month from baseline.
Locations:
city: Guiyang
country: China
facility: Guizhou Provincial People's Hospital
state: Guizhou
Study officials:
affiliation: Guizhou Provincial People's Hospital
name: Hao Zhou
role: PRINCIPAL_INVESTIGATOR
References: