Evaluating the Efficacy and Safety of Yi-Gan San in Children and Adolescents With Tourette's Disorder

Study Overview
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Brief Summary
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Yigansan was used in Ming dynasty by Xue Kai as a remedy for restlessness and agitation in children. We expect that the total YGTSS scores of Yigansan-treated subjects will be significantly reduced compared to that of placebo-treated subjects.

Detailed Description
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Tourette's disorder (TD) is a chronic, childhood-onset neuropsychiatric disorder. It is characterized by multiple motor and vocal tics, including involuntary or semivoluntary, sudden, brief, intermittent, repetitive movements or sounds. Yigansan was used in several clinical trials, like dementia, pervasive developmental disorder, schizophrenia and Huntington's disease, with good results. So the investigators choose Yigansan as a Chinese medicine formula in this study. After the participants signed the consent form, they have to stop taking any Chinese medicine or western medicine for treating Tourette's disorder for two weeks and then are randomly assigned to Yigansan group or placebo group. Our hypothesis is that Yigansan will be expected to improve motor tics and vocal tics, and YGTSS scores will decrease after 4-weeks treatments; secondary outcomes are measured by CGI-TS (Clinical Global Impression-Tourette Syndrome) scale and GTS-QOL (The Gilles de la Tourette syndrome-quality of life scale), and the investigators will also proceed the basic research of metabolomics and biochemistry(GOT、GPT、BUN、Creatinine、K+). In order to ensure the relationship of Tourette's disorder and allergic rhinitis, the investigators will detect IgE. Besides, the investigators will collect blood and urine from every child or adolescent when a participant visits our clinic at week 0 and week 4. In order to find these biomarkers related to TD, the investigators will use ELISA kits to detect and quantitate significantly changeable concentration of cytokines associated with YGTSS scores. In addition to specific cytokine targets, the investigators will also find these metabolites involved in TD between two groups before and after taking YGS. The serum and urine samples will be prepared and subjected to LC-MS/MS analysis. In summary of the experimental designs and expected results, the therapy and background information will be more clarified on the therapeutic efficacy and safety by Yigansan treatment for TD. Most importantly, this study will provide a kind of Chinese medicine formula to relieve such a disorder that most doctors feel difficult to treat.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Efficacy and Safety of Yi-Gan San in Children and Adolescents With Tourette's Disorder

Conditions
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Tourette Disorder, Tic Disorders

Intervention / Treatment
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* Drug: Yigansan
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject is a male or female child or adolescent, 6 to 17 years of age (inclusive) at the time of signing the informed consent/assent. The subject meets current DSM-V diagnostic criteria for Tourette's Disorder. The subject has a total score of ≥ 20 on the YGTSS at Screening and Baseline (randomization). Tic symptoms may cause impairment in the subject's normal routines, which include academic achievement, occupational functioning, social activities, and/or relationships. Females of childbearing potential (defined by menarche and not having undergone surgical sterilization/hysterectomy) must have a negative urine pregnancy test (when visiting our clinic at week 0 and week 4). Exclusion Criteria: The subject presents with a clinical presentation and/or history that is consistent with another neurologic condition that may have accompanying abnormal movements. These include, but are not limited to: Transient Tic disorder/ Huntington's disease/ Parkinson's disease/ Sydenham's chorea/ Wilson's disease/ Mental retardation/ Pervasive developmental disorder/ Traumatic brain injury/ Stroke/ Restless Legs Syndrome The subject has a history of schizophrenia, bipolar disorder, or other psychotic disorder. Subjects who receive psychostimulants for the treatment of ADD/ADHD and who have developed and/or had exacerbations of the tic disorder after the initiation of stimulant treatment. Subjects who ever participated in any Chinese medicine or western medicine trial within 30 days. Subjects requiring cognitive-behavioral therapy (CBT) for Tourette's Disorder during the trial period. The inability to swallow Chinese herbal medicine. Female subjects who have been pregnant.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 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: Yigansan<br>2.5g of Yigansan granules by mouth, three times a day for 4 weeks | Drug: Yigansan<br>* Yigansan granules<br>* Other names: YGS;|
| Placebo Comparator: Placebo<br>2.5g of Placebo(contained one-tenth Yigansan) granules by mouth, three times a day for 4 weeks | Drug: Placebo<br>* One-tenth concentration of Yigansan manufactured to mimic Yigansan granules<br>* Other names: Placebo (for Yigansan);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to Week 4 in Yale Global Tic Severity Scale (YGTSS) total tic score (TTS) | Ratings are 5 different dimensions on a scale of 0 to 5 for motor and vocal tics each, including number, frequency, intensity, complexity, and interference. The scores of TTS are from 0 to 50 and the scores of impairment are also from 0 to 50. Summation of TTS and impairment are YGTSS scores which will be the primary outcome measure in this trial. | Baseline to Week4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Clinical Global Impressions Scale-Tourette's Syndrome (CGI-TS) Score at Week 4 | Response choices included: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill patients. The change score was obtained from CGI-TS improvement scale assessment: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. | Baseline to Week 4 | 
| Mean change from Baseline to Endpoint (Week 4) in Total YGTSS Score | The YGTSS is used to rate the severity of symptoms (on a scale of 0 to 5 for 5 different dimensions, including number, frequency, intensity, complexity, and interference) of motor and vocal tics, and an impairment ranking. The Total YGTSS score is the summation of the severity scores of motor and vocal tics and also the ranking of impairment (range of 0 to 100). | Baseline to Week 4 | 
| Response Rate | Clinical response is defined as > 25% improvement from baseline to Week 4 in YGTSS TTS between 2 groups or a CGI-TS Change score of 1 [very much improved] or 2 [much improved] at Week 4. | Week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Yigansan, YGTSS