Clinical trial NCT03564132: Evaluating the Efficacy and Safety of Yi-Gan San in Children and Adolescents With Tourette's Disorder
Official title: A Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Efficacy and Safety of Yi-Gan San in Children and Adolescents With Tourette's Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Tourette Disorder
Tic Disorders
Keywords: Yigansan
YGTSS
Lead sponsor: China Medical University Hospital
Sponsor class: OTHER
First posted: 2018-06-20
Enrollment: 38
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. The subject meets current DSM-V diagnostic criteria for Tourette's Disorder.
3. The subject has a total score of ≥ 20 on the YGTSS at Screening and Baseline (randomization).
4. Tic symptoms may cause impairment in the subject's normal routines, which include academic achievement, occupational functioning, social activities, and/or relationships.
5. 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:

1. 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
2. The subject has a history of schizophrenia, bipolar disorder, or other psychotic disorder.
3. 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.
4. Subjects who ever participated in any Chinese medicine or western medicine trial within 30 days.
5. Subjects requiring cognitive-behavioral therapy (CBT) for Tourette's Disorder during the trial period.
6. The inability to swallow Chinese herbal medicine.
7. Female subjects who have been pregnant.

Primary outcomes:
measure: Change from Baseline to Week 4 in Yale Global Tic Severity Scale (YGTSS) total tic score (TTS)
timeFrame: Baseline to Week4
Secondary outcomes:
measure: Change in Clinical Global Impressions Scale-Tourette's Syndrome (CGI-TS) Score at Week 4
timeFrame: Baseline to Week 4
measure: Mean change from Baseline to Endpoint (Week 4) in Total YGTSS Score
timeFrame: Baseline to Week 4
measure: Response Rate
timeFrame: Week 4
Other outcomes:
Locations:
city: Taichung
country: Taiwan
facility: China Medical University Hospital
Study officials:
affiliation: China Medical University Hospital
name: Cheng-Hao Huang
role: PRINCIPAL_INVESTIGATOR
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