xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05980520</url>
    </required_header>
    <id_info>
      <org_study_id>20230702</org_study_id>
      <nct_id>NCT05980520</nct_id>
    </id_info>
    <brief_title>Study on the Treatment of Taurine in Children With Autism</brief_title>
    <official_title>Taurine Supplementation Improves Core Symptoms in Children With Autism Spectrum Disorders: a Randomized, Double-blinded, Controlled Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Guizhou Provincial People's Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Guizhou Provincial People's Hospital</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        In the treatment of autism spectrum disorders (ASD), medication is only an adjunct, and the&#xD;
        main treatment modalities are education and behavioral therapy. People with autism incur huge&#xD;
        medical and educational costs, which puts a great financial burden on families.Taurine is one&#xD;
        of the abundant amino acids in tissues and organs, and plays a variety of physiological and&#xD;
        pharmacological functions in nervous, cardiovascular, renal, endocrine and immune systems. A&#xD;
        large number of studies have shown that taurine can improve cognitive function impairment&#xD;
        under various physiological or pathological conditions through a variety of mechanisms,&#xD;
        taurine can increase the abundance of beneficial bacteria in the intestine, inhibit the&#xD;
        growth of harmful bacteria, and have a positive effect on intestinal homeostasis. This study&#xD;
        intends to analyze the effect of taurine supplementation on ASD, and explore the possible&#xD;
        mechanism by detecting intestinal symptoms, intestinal flora, markers of oxidative stress and&#xD;
        clinical symptoms of ASD.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Autism spectrum disorders (ASD) are the most common disabling disorders in childhood and are&#xD;
        characterized by social difficulties, stereotyped behavior, narrow interests and paresthesia.&#xD;
        In recent years, the prevalence of ASD has been increasing year by year, and the latest&#xD;
        epidemiology in the United States shows that the prevalence of ASD is 1/44. The previous&#xD;
        multi-center epidemiological survey of ASD in children in China showed that the prevalence of&#xD;
        ASD in children aged 6-12 in China was about 0.7%, and the lifetime medical and non-medical&#xD;
        expenses of ASD patients ranged from $1.4 million to $2.4 million. The survey showed that the&#xD;
        disease burden of ASD in children aged 0-6 in Guizhou Province was between 60,000 and 80,000&#xD;
        yuan/year/person. ASD has become a major public health problem affecting children's health&#xD;
        due to its high prevalence rate, disability rate and heavy disease burden, which has brought&#xD;
        huge economic and social burden to families and society of children with ASD. At present, ASD&#xD;
        has been listed as the leading disabling disease among mental diseases, bringing serious&#xD;
        burden to families and society, and ASD has become a major public health problem affecting&#xD;
        children's health.&#xD;
  &#xD;
        At present, there are no specific drugs to improve the core symptoms of ASD, and education&#xD;
        and behavioral therapy are mainly focused on early intervention to obtain the best results.&#xD;
        Although effective behavioral interventions can significantly improve the core symptoms of&#xD;
        children with ASD, a significant proportion of children with ASD still have residual&#xD;
        functional disabilities. Therefore, the research and development of new treatment methods for&#xD;
        children with ASD has become a hot and difficult problem. Children with ASD are prone to&#xD;
        multiple nutrients due to poor eating habits, gastrointestinal symptoms and food allergies,&#xD;
        and the addition of key nutrients is expected to become one of the important adjuvant&#xD;
        treatments for children with ASD. The project team established a national children's ASD&#xD;
        multi-center research cohort and built a children's ASD biobank under the financial support&#xD;
        of the National Health Commission. A case-control (117:119) study using 1H-NMR metabolomics&#xD;
        to detect urine samples of children with ASD showed lower taurine levels in the ASD group&#xD;
        compared to the healthy control group. In recent years, taurine deficiency has been linked to&#xD;
        neurological disorders or symptoms such as neurodegenerative diseases, stroke, epilepsy, and&#xD;
        diabetic neuropathy. In addition, animal and clinical experiments have found that taurine&#xD;
        supplementation has certain therapeutic effects on neurological diseases including Angelman&#xD;
        behavior sign, fragile X behavior sign, sleep-wake disorder, stroke, attention deficit&#xD;
        hyperactivity disorder, tic disorder, and taurine supplementation can improve anxiety&#xD;
        symptoms and cognitive ability of mice. In previous animal intervention experiment, taurine&#xD;
        supplementation on the basis of VPA autism model in rats during pregnancy was found to&#xD;
        improve ASD-like behavior in offspring. However, there is a lack of population-based evidence&#xD;
        in children with ASD.&#xD;
  &#xD;
        Taurine is widely distributed in brain, spinal cord, heart, muscle cells and retina, and is&#xD;
        one of the more abundant amino acids in almost all tissues and organs. A large number of&#xD;
        studies have shown that taurine can protect a variety of tissues and organs from oxidative&#xD;
        stress damage. Taurine can also ameliorate cognitive impairment in a variety of physiological&#xD;
        and pathological conditions through a variety of mechanisms, including reducing&#xD;
        neuroinflammation, up-regulating Nrf2 expression and antioxidant capacity, activating&#xD;
        Akt/CREB/PGC1α signaling pathway to further enhance mitochondrial biosynthesis, synaptic&#xD;
        function, and reducing oxidative stress. A large number of studies have shown that compared&#xD;
        with healthy controls, the blood levels of oxidative stress markers in children with ASD are&#xD;
        reduced or increased to varying degrees, and are thought to be related to the formation of&#xD;
        stereotypical behaviors of ASD. Whether taurine can improve the core symptoms of ASD by&#xD;
        reducing oxidative stress damage remains unclear, and human studies are needed to further&#xD;
        clarify the mechanism of action and verify the findings of animal experiments.&#xD;
  &#xD;
        In summary, taurine deficiency is closely related to the onset of neurodevelopmental&#xD;
        disorders, and dietary supplementation may have a certain therapeutic effect. This study is&#xD;
        based on this starting point to propose the basis of project. This study intends to conduct&#xD;
        an exploratory randomized, double-blind controlled trial to compare and analyze the effect of&#xD;
        taurine supplementation on the improvement of core symptoms in ASD children who were treated&#xD;
        with routine behavioral rehabilitation combined with taurine supplement (experimental group)&#xD;
        and behavioral rehabilitation combined with placebo (control group) for 3 months and&#xD;
        continued follow-up for 12 months. The possible mechanism of action was investigated by&#xD;
        detecting intestinal symptoms, intestinal flora, markers of oxidative stress and clinical&#xD;
        symptoms of ASD. The aim of this study is to explore an effective and reliable adjuvant&#xD;
        therapy for children with ASD. To investigate the curative effect of taurine supplementation&#xD;
        on the core symptoms of children with ASD spectrum disorder. To observe the incidence of&#xD;
        adverse reactions of taurine supplementation, evaluate the clinical application value of&#xD;
        taurine supplementation, and provide theoretical support for further tests.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 2023</start_date>
    <completion_date type="Anticipated">August 2024</completion_date>
    <primary_completion_date type="Anticipated">August 2024</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Score of Autism Treatment Evaluation Checklist (ATEC)</measure>
      <time_frame>From baseline till the 12th month.</time_frame>
      <description>Autism Treatment Evaluation Checklist (ATEC) will be used to evaluate the rehabilitation of ASD core syndromes after interventions, which includes communication, social, perception skills and healthy behaviors. ATEC will be self-assessed by guardians.Severity grading: mild (initial ATEC score 20-49), moderate (initial ATEC score 50-79), severe (initial ATEC score &gt;80). The lower the ATEC scores, the better the rehabilitation.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Score of Autism Treatment Evaluation Checklist (ATEC)</measure>
      <time_frame>From baseline till the 1st,2rd,3rd,6th,9th month.</time_frame>
      <description>Autism Treatment Evaluation Checklist (ATEC) will be used to evaluate the rehabilitation of ASD core syndromes after interventions, which includes communication, social, perception skills and healthy behaviors. ATEC will be self-assessed by guardians.Severity grading: mild (initial ATEC score 20-49), moderate (initial ATEC score 50-79), severe (initial ATEC score &gt;80). The lower the ATEC scores, the better the rehabilitation.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Childhood Autism Rating Scale(CARS)</measure>
      <time_frame>At the1st,2rd,3rd,6th,9th,12th month from baseline.</time_frame>
      <description>The Childhood Autism Rating Scale (CARS) developed by Schoplen(1980).The total score is 60 points, and CARS will be evaluated by clinicians. Participants with a score15-30,31-36,37-60 are considered as mild autism, moderate autism, severe autism.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>6-item Gastrointestinal Severity Index(6-GSI)</measure>
      <time_frame>At the1st,2rd,3rd,6th,9th,12th month from baseline.</time_frame>
      <description>6-item Gastrointestinal Severity Index(6-GSI) will be used to assess the Gastrointestinal syndromes of ASD patients, including constipation, diarrhea, average stool consistency, stool smell, flatulence, abdominal pain. The higher the score, the more severe the syndromes.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Autism Spectrum Rating Scales(ASRS)</measure>
      <time_frame>At the1st,2rd,3rd,6th,9th,12th month from baseline.</time_frame>
      <description>The Autism Spectrum Rating Scales (ASRS), consisting of 71 questions, consists of three core parts: defects in the nature of social interaction, abnormalities in language and communication, stereotypes, limitations, and repetitive interests and behaviors.&#xD;
  ASRS will be self-assessed by guardians. The ASRS questionnaire uses a 5-level score: 0 = never, meaning that it has never happened; 1 point = very few, refers to 1 or 2 times in a month; 2 points = sometimes, refers to 1 or 2 times in a week; 3 points = frequent, meaning 3 or 4 times in a week; 4 points = always, which means every day.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Social Responsiveness Scale(SRS)</measure>
      <time_frame>At the1st,2rd,3rd,6th,9th,12th month from baseline.</time_frame>
      <description>Social Responsiveness Scale (SRS), which quantifies children's social ability, are used to assess children's social ability. SRS will be self-assessed by guardians. There are five subscales: Social Awareness, Social Cognition, Social Communication and Social motivation And Autistic Mannerisms. The main feature of this scale is to evaluate the social situation of children closely with social disorder as the core symptom of ASD.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Identification and Management of Feeding Difficulties(IMFeD)</measure>
      <time_frame>At the1st,2rd,3rd,6th,9th,12th month from baseline.</time_frame>
      <description>Identification and Management of Feeding Difficulties(IMFeD), it is composed of 17 items and contains six dimensions: poor appetite, particular food preferences, poor eating habits, excessive parental concern, fear of eating, and underlying disease status. IMFeD will be self-assessed by guardians. The severity of children's eating behavior problems is divided into four levels: &quot;Always&quot; refers to an average of 5 or more days per week when the eating behavior or feeling.&quot;Often&quot; means having this behavior or feeling on average 3 to 4 days per week.&quot;Sometimes&quot; means having this behavior or feeling on average 1 to 2 days per week.&quot;Never&quot; means that the action or feeling does not occur.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Gesell Developmental Scale</measure>
      <time_frame>At the1st,2rd,3rd,6th,9th,12th month from baseline.</time_frame>
      <description>The Gesell developmental scale mainly assesses the function of the central nervous system. It has five specific domains, gross motor, fine motor, language and individual-social behavior. Gesell Developmental Scale will be evaluated by clinicians.According to the relationship between the scores obtained in 5 behavioral fields and actual age, the development quotient(DQ) of each field was calculated. Edge state: 76≤DQ≤85; Mild stunting: 55≤DQ≤75; Moderate stunting: 40≤DQ≤54; Severe stunting: 25≤DQ≤39; Very severe stunting: DQ&lt;25.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Children's Sleep Habits Questionnaire (CSHQ)</measure>
      <time_frame>At the1st,2rd,3rd,6th,9th,12th month from baseline.</time_frame>
      <description>Children's Sleep Habits Questionnaire (CSHQ), which contains 48 items, can detect eight specific sleep problems, such as bad sleeping habits, sleep anxiety, irregular sleep duration, sleep disordered breathing, abnormal sleep, daytime sleepiness, night waking, and prolonged sleep latency. CSHQ will be self-assessed by guardians. The CSHQ asked parents to recall their children's sleep conditions in the past four weeks, and rated the children's sleep conditions as &quot;often&quot; (5-7 times per week), &quot;sometimes&quot; (2-4 times per week), and &quot;rarely or none&quot; (0-1 times per week).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Body mass index(BMI) Z score</measure>
      <time_frame>At the1st,2rd,3rd,6th,9th,12th month from baseline.</time_frame>
      <description>Height(cm) and weight(kg) will be measured at each visit. BMI will be calculated as weight(kg)/[(height(cm)/100)^2 ]. Z score of BMI for age and gender will be computed based on the current national reference (2020).</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">60</enrollment>
    <condition>Autism Spectrum Disorder</condition>
    <arm_group>
      <arm_group_label>Taurine treatment group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Taurine combined with behavioral rehabilitation therapy</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo group</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Placebo combined with behavioral rehabilitation therapy</description>
    </arm_group>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Taurine+corn starch+white sugar</intervention_name>
      <description>Taurine granules mixed with corn starch and white sugar, 0.4g in 1 bag, taken orally. One time dosage: 1 bag each time for 1-2 years old, 3 times a day, 1.5 bags each time for 3-5 years old, 3 times a day, 2 bags each time for 6-8 years old, 3 times a day, 2.5-3 bags each time for 9-13 years old, 3 to 4 bags each time for children and adults over 14 years old, 3 times a day. The use of taurine is strictly in accordance with the specifications of Chinese Pharmacopoeia.</description>
      <arm_group_label>Taurine treatment group</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Corn starch+white sugar</intervention_name>
      <description>0.4g in 1 bag, taken orally. One time dosage: 1 bag each time for 1-2 years old, 3 times a day, 1.5 bags each time for 3-5 years old, 3 times a day, 2 bags each time for 6-8 years old, 3 times a day, 2.5-3 bags each time for 9-13 years old, 3 to 4 bags each time for children and adults over 14 years old, 3 times a day.</description>
      <arm_group_label>Placebo group</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>Behavioral rehabilitation therapy</intervention_name>
      <description>Structured training courses which included: visual arrangement, routine, environmental arrangement, program schedule, personal work system consists of five parts. The course is designed and implemented by qualified behavioral rehabilitators who have worked for more than 5 years, with the participation of parents. The daily training time is about 6-8 hours, and the total intervention time is not less than 40 hours per week.</description>
      <arm_group_label>Placebo group</arm_group_label>
      <arm_group_label>Taurine treatment group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Aged 2.5-18 years at enrollment.&#xD;
  &#xD;
            -  Meet the diagnosis criteria of ASD by the diagnostic and statistical manual of mental&#xD;
               disorders(DSM-5).&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Rett behavioral sign, cerebral palsy, other congenital diseases, associated with other&#xD;
               inherited metabolic behavioral signs, epilepsy.&#xD;
  &#xD;
            -  Children who have had an acute or chronic infectious disease in the past 3 months.&#xD;
  &#xD;
            -  Children with abnormal liver and kidney function, chronic pulmonary heart disease.&#xD;
  &#xD;
            -  Children who have taken taurine supplements or medications in the past 3 months.&#xD;
  &#xD;
            -  Parents or patients refuse to participate in the study.&#xD;
  &#xD;
            -  The investigator determines that the subject is unable to comply with the study&#xD;
               requirements.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>30 Months</minimum_age>
      <maximum_age>18 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Hao Zhou</last_name>
      <role>Principal Investigator</role>
      <affiliation>Guizhou Provincial People's Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Xiangdi Yu, MD</last_name>
      <phone>008618212004663</phone>
      <email>XiangdiYu@163.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Guizhou Provincial People's Hospital</name>
        <address>
          <city>Guiyang</city>
          <state>Guizhou</state>
          <zip>550003</zip>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Hao Zhou, Doctor</last_name>
        <phone>008618586871915</phone>
        <email>zhouhaogz@sina.com</email>
      </contact>
      <contact_backup>
        <last_name>Qun Deng, Deng</last_name>
        <phone>008618984488277</phone>
        <email>2773478828@qq.com</email>
      </contact_backup>
      <investigator>
        <last_name>Zhong bi Peng, Master</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 31, 2023</study_first_submitted>
    <study_first_submitted_qc>July 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 8, 2023</study_first_posted>
    <last_update_submitted>August 8, 2023</last_update_submitted>
    <last_update_submitted_qc>August 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 9, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>autism spectrum disorders</keyword>
    <keyword>children</keyword>
    <keyword>taurine</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Autistic Disorder</mesh_term>
      <mesh_term>Autism Spectrum Disorder</mesh_term>
      <mesh_term>Child Development Disorders, Pervasive</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05980520
  org study id: 20230702
  nct id: NCT05980520
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  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.
  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.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  measure: Score of Autism Treatment Evaluation Checklist (ATEC)
  time frame: From baseline till the 12th month.
  description: Autism Treatment Evaluation Checklist (ATEC) will be used to evaluate the rehabilitation of ASD core syndromes after interventions, which includes communication, social, perception skills and healthy behaviors. ATEC will be self-assessed by guardians.Severity grading: mild (initial ATEC score 20-49), moderate (initial ATEC score 50-79), severe (initial ATEC score >80). The lower the ATEC scores, the better the rehabilitation.
  measure: Score of Autism Treatment Evaluation Checklist (ATEC)
  time frame: From baseline till the 1st,2rd,3rd,6th,9th month.
  description: Autism Treatment Evaluation Checklist (ATEC) will be used to evaluate the rehabilitation of ASD core syndromes after interventions, which includes communication, social, perception skills and healthy behaviors. ATEC will be self-assessed by guardians.Severity grading: mild (initial ATEC score 20-49), moderate (initial ATEC score 50-79), severe (initial ATEC score >80). The lower the ATEC scores, the better the rehabilitation.
  measure: Childhood Autism Rating Scale(CARS)
  time frame: At the1st,2rd,3rd,6th,9th,12th month from baseline.
  description: The Childhood Autism Rating Scale (CARS) developed by Schoplen(1980).The total score is 60 points, and CARS will be evaluated by clinicians. Participants with a score15-30,31-36,37-60 are considered as mild autism, moderate autism, severe autism.
  measure: 6-item Gastrointestinal Severity Index(6-GSI)
  time frame: At the1st,2rd,3rd,6th,9th,12th month from baseline.
  description: 6-item Gastrointestinal Severity Index(6-GSI) will be used to assess the Gastrointestinal syndromes of ASD patients, including constipation, diarrhea, average stool consistency, stool smell, flatulence, abdominal pain. The higher the score, the more severe the syndromes.
  measure: Autism Spectrum Rating Scales(ASRS)
  time frame: At the1st,2rd,3rd,6th,9th,12th month from baseline.
  description: The Autism Spectrum Rating Scales (ASRS), consisting of 71 questions, consists of three core parts: defects in the nature of social interaction, abnormalities in language and communication, stereotypes, limitations, and repetitive interests and behaviors.
  ASRS will be self-assessed by guardians. The ASRS questionnaire uses a 5-level score: 0 = never, meaning that it has never happened; 1 point = very few, refers to 1 or 2 times in a month; 2 points = sometimes, refers to 1 or 2 times in a week; 3 points = frequent, meaning 3 or 4 times in a week; 4 points = always, which means every day.
  measure: Social Responsiveness Scale(SRS)
  time frame: At the1st,2rd,3rd,6th,9th,12th month from baseline.
  description: Social Responsiveness Scale (SRS), which quantifies children's social ability, are used to assess children's social ability. SRS will be self-assessed by guardians. There are five subscales: Social Awareness, Social Cognition, Social Communication and Social motivation And Autistic Mannerisms. The main feature of this scale is to evaluate the social situation of children closely with social disorder as the core symptom of ASD.
  measure: Identification and Management of Feeding Difficulties(IMFeD)
  time frame: At the1st,2rd,3rd,6th,9th,12th month from baseline.
  description: Identification and Management of Feeding Difficulties(IMFeD), it is composed of 17 items and contains six dimensions: poor appetite, particular food preferences, poor eating habits, excessive parental concern, fear of eating, and underlying disease status. IMFeD will be self-assessed by guardians. The severity of children's eating behavior problems is divided into four levels: "Always" refers to an average of 5 or more days per week when the eating behavior or feeling."Often" means having this behavior or feeling on average 3 to 4 days per week."Sometimes" means having this behavior or feeling on average 1 to 2 days per week."Never" means that the action or feeling does not occur.
  measure: Gesell Developmental Scale
  time frame: At the1st,2rd,3rd,6th,9th,12th month from baseline.
  description: The Gesell developmental scale mainly assesses the function of the central nervous system. It has five specific domains, gross motor, fine motor, language and individual-social behavior. Gesell Developmental Scale will be evaluated by clinicians.According to the relationship between the scores obtained in 5 behavioral fields and actual age, the development quotient(DQ) of each field was calculated. Edge state: 76≤DQ≤85; Mild stunting: 55≤DQ≤75; Moderate stunting: 40≤DQ≤54; Severe stunting: 25≤DQ≤39; Very severe stunting: DQ<25.
  measure: Children's Sleep Habits Questionnaire (CSHQ)
  time frame: At the1st,2rd,3rd,6th,9th,12th month from baseline.
  description: Children's Sleep Habits Questionnaire (CSHQ), which contains 48 items, can detect eight specific sleep problems, such as bad sleeping habits, sleep anxiety, irregular sleep duration, sleep disordered breathing, abnormal sleep, daytime sleepiness, night waking, and prolonged sleep latency. CSHQ will be self-assessed by guardians. The CSHQ asked parents to recall their children's sleep conditions in the past four weeks, and rated the children's sleep conditions as "often" (5-7 times per week), "sometimes" (2-4 times per week), and "rarely or none" (0-1 times per week).
  measure: Body mass index(BMI) Z score
  time frame: At the1st,2rd,3rd,6th,9th,12th month from baseline.
  description: Height(cm) and weight(kg) will be measured at each visit. BMI will be calculated as weight(kg)/[(height(cm)/100)^2 ]. Z score of BMI for age and gender will be computed based on the current national reference (2020).
  arm group label: Taurine treatment group
  arm group type: Experimental
  description: Taurine combined with behavioral rehabilitation therapy
  arm group label: Placebo group
  arm group type: Placebo Comparator
  description: Placebo combined with behavioral rehabilitation therapy
  intervention type: Dietary Supplement
  intervention name: Taurine+corn starch+white sugar
  description: Taurine granules mixed with corn starch and white sugar, 0.4g in 1 bag, taken orally. One time dosage: 1 bag each time for 1-2 years old, 3 times a day, 1.5 bags each time for 3-5 years old, 3 times a day, 2 bags each time for 6-8 years old, 3 times a day, 2.5-3 bags each time for 9-13 years old, 3 to 4 bags each time for children and adults over 14 years old, 3 times a day. The use of taurine is strictly in accordance with the specifications of Chinese Pharmacopoeia.
  arm group label: Taurine treatment group
  intervention type: Dietary Supplement
  intervention name: Corn starch+white sugar
  description: 0.4g in 1 bag, taken orally. One time dosage: 1 bag each time for 1-2 years old, 3 times a day, 1.5 bags each time for 3-5 years old, 3 times a day, 2 bags each time for 6-8 years old, 3 times a day, 2.5-3 bags each time for 9-13 years old, 3 to 4 bags each time for children and adults over 14 years old, 3 times a day.
  arm group label: Placebo group
  intervention type: Behavioral
  intervention name: Behavioral rehabilitation therapy
  description: Structured training courses which included: visual arrangement, routine, environmental arrangement, program schedule, personal work system consists of five parts. The course is designed and implemented by qualified behavioral rehabilitators who have worked for more than 5 years, with the participation of parents. The daily training time is about 6-8 hours, and the total intervention time is not less than 40 hours per week.
  arm group label: Placebo group
  arm group label: Taurine treatment group
  criteria: 
  gender: All
  minimum age: 30 Months
  maximum age: 18 Years
  healthy volunteers: No
  last name: Hao Zhou
  role: Principal Investigator
  affiliation: Guizhou Provincial People's Hospital
  last name: Xiangdi Yu, MD
  phone: 008618212004663
  email: XiangdiYu@163.com
  facility: 
  contact: 
  contact backup: 
  investigator: 
  country: China
  responsible party type: Sponsor
  mesh term: Autistic Disorder
  mesh term: Autism Spectrum Disorder
  mesh term: Child Development Disorders, Pervasive
  sharing ipd: No