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

Tic Disorders Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03564132
• Other study ID #: CMUH106-REC2-148
• Status: Completed
• Phase: Phase 2
• Start date: June 16, 2018
• Est. completion date: August 31, 2022

Study information

• Verified date: April 2023
• Source: China Medical University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: August 31, 2022
• Est. primary completion date: August 15, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Disease
• Tic Disorders
• Tourette Disorder
• Tourette Syndrome

Intervention

Drug:
• Yigansan
Yigansan granules
• Placebo
One-tenth concentration of Yigansan manufactured to mimic Yigansan granules

Locations

Country	Name	City	State
Taiwan	China Medical University Hospital	Taichung

Sponsors (1)

Lead Sponsor	Collaborator
China Medical University Hospital

Country where clinical trial is conducted

Taiwan, 

References & Publications (12)

Chou IC, Lin HC, Lin CC, Sung FC, Kao CH. Tourette syndrome and risk of depression: a population-based cohort study in Taiwan. J Dev Behav Pediatr. 2013 Apr;34(3):181-5. doi: 10.1097/DBP.0b013e3182829f2b. — View Citation

Cohen SC, Leckman JF, Bloch MH. Clinical assessment of Tourette syndrome and tic disorders. Neurosci Biobehav Rev. 2013 Jul;37(6):997-1007. doi: 10.1016/j.neubiorev.2012.11.013. Epub 2012 Dec 1. — View Citation

Eddy CM, Rickards HE, Cavanna AE. Treatment strategies for tics in Tourette syndrome. Ther Adv Neurol Disord. 2011 Jan;4(1):25-45. doi: 10.1177/1756285610390261. — View Citation

Jankovic J. Tourette's syndrome. N Engl J Med. 2001 Oct 18;345(16):1184-92. doi: 10.1056/NEJMra010032. No abstract available. — View Citation

Kim YH, Son CG, Ku BC, Lee HW, Lim HS, Lee MS. Herbal medicines for treating tic disorders: a systematic review of randomised controlled trials. Chin Med. 2014 Feb 7;9(1):6. doi: 10.1186/1749-8546-9-6. — View Citation

Miyaoka T, Furuya M, Horiguchi J, Wake R, Hashioka S, Thoyama M, Murotani K, Mori N, Minabe Y, Iyo M, Ueno S, Ezoe S, Hoshino S, Seno H. Efficacy and safety of yokukansan in treatment-resistant schizophrenia: a randomized, multicenter, double-blind, placebo-controlled trial. Evid Based Complement Alternat Med. 2015;2015:201592. doi: 10.1155/2015/201592. Epub 2015 Apr 14. — View Citation

Miyaoka T, Furuya M, Horiguchi J, Wake R, Hashioka S, Tohyama M, Mori N, Minabe Y, Iyo M, Ueno S, Ezoe S, Murotani K, Hoshino S, Seno H. Efficacy and safety of yokukansan in treatment-resistant schizophrenia: a randomized, double-blind, placebo-controlled trial (a Positive and Negative Syndrome Scale, five-factor analysis). Psychopharmacology (Berl). 2015 Jan;232(1):155-64. doi: 10.1007/s00213-014-3645-8. Epub 2014 Jun 13. — View Citation

Takeyoshi K, Kurita M, Nishino S, Teranishi M, Numata Y, Sato T, Okubo Y. Yokukansan improves behavioral and psychological symptoms of dementia by suppressing dopaminergic function. Neuropsychiatr Dis Treat. 2016 Mar 15;12:641-9. doi: 10.2147/NDT.S99032. eCollection 2016. — View Citation

Wang S, Qi F, Li J, Zhao L, Li A. Effects of Chinese herbal medicine Ningdong granule on regulating dopamine (DA)/serotonin (5-TH) and gamma-amino butyric acid (GABA) in patients with Tourette syndrome. Biosci Trends. 2012 Aug;6(4):212-8. doi: 10.5582/bst.2012.v6.4.212. — View Citation

Wu M, Xiao GH, Zhang JM, Zhang X, Ma B, Wang SX, Zhou YB, Zhang JY. Clinical research into Qufeng Zhidong Recipe used to treat 31 children with tic disorder. J Tradit Chin Med. 2010 Sep;30(3):163-70. doi: 10.1016/s0254-6272(10)60034-9. — View Citation

Zhao L, Li AY, Lv H, Liu FY, Qi FH. Traditional Chinese medicine Ningdong granule: the beneficial effects in Tourette's disorder. J Int Med Res. 2010 Jan-Feb;38(1):169-75. doi: 10.1177/147323001003800119. — View Citation

Zheng Y, Zhang ZJ, Han XM, Ding Y, Chen YY, Wang XF, Wei XW, Wang MJ, Cheng Y, Nie ZH, Zhao M, Zheng XX. A proprietary herbal medicine (5-Ling Granule) for Tourette syndrome: a randomized controlled trial. J Child Psychol Psychiatry. 2016 Jan;57(1):74-83. doi: 10.1111/jcpp.12432. Epub 2015 Jun 13. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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