A Study of Bumetanide for the Treatment of Autism Spectrum Disorders

Study Overview
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Brief Summary
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The investigators are going to carry out a randomized double-blind placebo-controlled trial to study the efficiency and mechanism of bumetanide on the treatment of children with Autism Spectrum Disorder.

Detailed Description
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In consideration of the increasing number of autistic children and poor intervention effect in China, it is an urgent to find some effective medicine. Some studies have reported bumetanide, a classic diuretic, could improve autistic behaviors in both animal model and humans; while the efficiency of bumetanide on Chinese autistic chilren is unkonwn and the underlying mechanisms remain unfolding. The investigators aim at investigating whether bumetanide would improve the clinical symptoms in Chinese children with autism within a safe dosage and further study the physiological mechanism beneath.The investigators will regularly assess the participants' autism-related symptoms during medication, as well as the adverse effects of each patient. The investigators will carry out genome-wide association analysis (GWAS) from blood sample, related metabolites in nervous system and compare the concentration of the neurotransmitter in autistic brain before and after 3 months' treatmeat,and also will collect the EEG signal in autistic chilldren when the participants performing certain tasks before and after 3 months' treatment.

Official Title
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A Study of Bumetanide for the Treatment of Children With Autism Spectrum Disorder：a Randomized Double-blind Placebo-controlled Trial

Conditions
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Autism Spectrum Disorder

Intervention / Treatment
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* Drug: Bumetanide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patients, aged from 3 to 6 years old, were given the diagnosis of ASD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) , by a team of autism experts; Scores for Children Autism Rating Scale (CARS) were more than 30; Signed Informed Consents were provided by parents. Exclusion Criteria: Liver and kidney dysfunction; With a history of allergy to sulfa drugs; abnormal ECG; chromosomal abnormality; suffering from nervous system diseases (such as epilepsy, schizophrenia, and so on); using the melatonin treatment for sleep disorders or withdrawal less than three weeks.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bumetanide group<br>Double-blind phase: in the first 3 months, patients will receive the experimental treatment - bumetanide, oral intake, 0.5mg/time, twice a day; Open-label phase: after 3 month double-blined treatment, all the patients will receive 3-month bumetanide treatment - oral intake, 0.5mg/time, twice a day. | Drug: Bumetanide<br>* bumetanide tablets, oral intake, 0.5mg, twice daily, respectively at 8 am and 4 pm<br>|
| Placebo Comparator: Control group<br>Double-blind phase: in the first 3 months, patients will receive the placebo - oral intake, 0.5mg/time, twice a day; Open-label phase: after 3 month double-blined treatment, patients in this group will receive 3-month bumetanide treatment - oral intake, 0.5mg/time, twice a day. | Drug: Placebo<br>* placebo tablets, oral intake, 0.5mg, twice daily, respectively at 8 am and 4 pm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Childhood Autism Rating Scale(CARS) | CARS is a behaviour-rating scale used to assess the presence and severity of the symptoms of autism spectrum disorder | Day 0 and Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impressions Scale (CGI) | CGI is a scale used to assess the severity of the illness and the global improvement of the patient under intervention | Day 0 and Day 90 | 
| Social Responsiveness Scale (SRS) | SRS is a questionnaire used to assess the presence and severity of social impairment. | Day 0 and Day 90 | 
| Autism Diagnostic Observation Schedule (ADOS) | The ADOS is a structured play session conducted by clinicians, with the total score combines the Social and Communication domain items. | Day 0 and Day 90 | 
| Short Sensory Profile Report | The Sensory Profile is a measure of children's responses to sensory events in daily life. The caregiver completes the Sensory Profile by assessing the frequency of the child's responses to certain sensory processing, modulation, and behavioral/emotional events as described in the 125 items. | Day 0 and Day 90 | 
| Symbolic Play Test | Symbolic Play Test is a nonverbal measure of symbolic functioning in participants aged 12-36 months. The test does not require any expressive speech, and is therefore appropriate for use with all participants with ASD. Participants are sequentially presented with four sets of toys, and their spontaneous manipulation of the objects is observed and recorded on a standardized checklist. | Day 0 and Day 90 | 
| Chinese Communicative Development Inventory | The Chinese Communicative Development Inventories (CCDI) is a questionnaire that is used to direct measures of the participants' language.Change between day 0 and day 90 of the result of the Chinese Communicative Development Inventory | Day 0 and Day 90 |