The Role of Probiotics PS128 in Movement Disorders

Study Overview
=================
Brief Summary
-----------------
Pediatric movement disorders comprise of a large number of different neurological diseases including Rett syndrome (RTT) and Tourette syndrome. Studies in the literature as well as our preliminary reports showed that Rett syndrome and Tourette syndrome/Tic disorders are associated with a dysbiosis of the gut microbiota compared to normal control. Probiotic Lactobacillus plantarum PS128 is a diet supplement that available for human consumption. Probiotic Lactobacillus plantarum PS128 had showed psychotropic effects such as ameliorate anxiety- and depression-like behaviors as well as altered the level of neurotransmitters such as dopamine in the brain in animal models, which might be through microbiota-gut-brain axis. Therefore, the purpose of this study is to access the possible neurobehavior effects of Probiotic Lactobacillus plantarum PS128 in Rett syndrome and Tic disorders/Tourette syndrome.

Detailed Description
-----------------
The study is a placebo-controlled double-blind randomized study, to determine the benefits of probiotic Lactobacillus plantarum PS128 vs placebo on symptoms for Tic disorders; and the symptoms, behavior, or cognition for Rett syndrome. Patients with the Rett syndrome and Tic disorders/Tourette syndrome will be recruited into our study.The study period will last 4 months for Rett syndrome patients, age one year-50years; while 2 months for Tic disorders/Tourette syndrome patient, age 5 years-18 years. The study will be performed in National Taiwan University Children Hospital. The patients will have neuropsychological and gut microbiota evaluation before and at the end of the study. There will also be interim follow up evaluations each month after the patient start taking the probiotic or placebo.

Official Title
-----------------
The Role of Probiotics PS128 in Movement Disorders

Conditions
-----------------
Rett Syndrome, Tourette Syndrome, Tic Disorders

Intervention / Treatment
-----------------
* Dietary Supplement: Probiotic-Lactobacillus plantarum PS128
* Dietary Supplement: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Rett syndrome: Males and females who have classic or atypical RTT diagnosed under consensus criteria Age: 1-50 years Tic disorders: males and females with clinical diagnosis Age: 8-18years Treatment naive 4 weeks prior to study Those with standard medications, dosage stable 4 weeks prior to study AADC syndrome: Males and females with AADC diagnosis Age: 1-50 years Exclusion Criteria: Those who took probiotic or probiotic related product 4 weeks prior to the study or during the study Those who took antibiotic 4 weeks prior to the study Those showing poor compliance with any aspect of the study Those had adverse reactions to PS128

Ages Eligible for Study
-----------------
Minimum Age: 1 Year
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo (for tic disorder)<br>The placebo will be dispensed to equal the volume of 1 tablet of Probiotic PS128, which is taken orally in 2 divided doses, 12 hours apart during the study period of 2 months for Tic disorders. | Dietary Supplement: Placebo<br>* placebo , 1 tablet , twice a day , 12 hrs apart, lasting 2 months for Tic disorders and 4 months for Rett syndrome<br>|
| Active Comparator: PS128 (tic disorder)<br>The Probiotic group in tic disorder will take Probiotic-Lactobacillus plantarum PS128, which contain 300mg (3x10^10 CFU) Lactobacillus plantarum PS128 and 100mg of Microcrystalline Cellulose in each tablet. It will be taken orally in 2 divided doses, 12 hours apart during the study period of 2 months for Tic disorders. | Dietary Supplement: Probiotic-Lactobacillus plantarum PS128<br>* Probiotic supplement of Lactobacillus plantarum PS128 , 1 tablet , twice a day , 12 hrs apart, lasting 2 months for Tic disorders and 4 months for Rett syndrome<br>* Other names: Lactobacillus plantarum PS128;|
| Placebo Comparator: Placebo (for Rett syndrome)<br>The placebo will be dispensed to equal the volume of 1 tablet of Probiotic PS128, which is taken orally in 2 divided doses, 12 hours apart during the study period of 4 months for Rett syndrome | Dietary Supplement: Placebo<br>* placebo , 1 tablet , twice a day , 12 hrs apart, lasting 2 months for Tic disorders and 4 months for Rett syndrome<br>|
| Active Comparator: PS128 (Rett syndrome)<br>The Probiotic group will take Probiotic-Lactobacillus plantarum PS128, which contain 300mg (3x10^10 CFU) Lactobacillus plantarum PS128 and 100mg of Microcrystalline Cellulose in each tablet. It will be taken orally in 2 divided doses, 12 hours apart during the study period of 4 months for Rett Syndrome. | Dietary Supplement: Probiotic-Lactobacillus plantarum PS128<br>* Probiotic supplement of Lactobacillus plantarum PS128 , 1 tablet , twice a day , 12 hrs apart, lasting 2 months for Tic disorders and 4 months for Rett syndrome<br>* Other names: Lactobacillus plantarum PS128;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuropsychological test (Mullen Scales of Early Learning) | for Rett syndrome | Change at four months from baseline | 
| Yale Global Tic Severity Scale (YGTSS) | for Tic disorders | Change at 2 months from baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RTT severity score | For Rett syndrome | Change at four months from baseline | 
| Dystonia status (Fahn Marsden rating scale/Unified Dystonia Rating Scale ) | For Rett syndrome | Visit 1, Visit 2, Visit 3, Visit 4 (Up to 4 months) | 
| Anxiety, Depression, and Mood Scale (ADAMS) | For Rett syndrome | Change at four months from baseline | 
| Ghuman-Folstein Screen for Social Interaction (SSI) | For Rett syndrome | Change at four months from baseline | 
| Vineland Adaptive Behavioral scale | For Rett syndrome | Change at four months from baseline | 
| Early social communication scales | For Rett syndrome | Change at four months from baseline | 
| Pediatric Evaluation of Disability Inventory | For Rett syndrome | Change at four months from baseline | 
| Stool and gut microbiota evaluation | For Rett and Tic disorders | Change at four months from baseline | 
| Child Behavior Checklist (CBCL) | For Tic disorders | Change at 2 months from baseline | 
| Continuous performance test | For Tic disorders | Change at 2 months from baseline | 
| The Migraine Disability Assessment Test | For Tic disorders | Change at 2 months from baseline | 
| Children's Depression Inventory | For Tic disorders | Change at 2 months from baseline | 
| Obsessive-compulsive inventory | For Tic disorders | Change at 2 months from baseline | 
| Swanson, Nolan and Pehlam version IV | For Tic disorders | Change at 2 months from baseline | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Rett syndrome, Tourette syndrome, Probiotic