The Role of Probiotics PS128 in Movement Disorders

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.

Study Overview

• Status: Unknown
• Conditions: Rett Syndrome; Tourette Syndrome; Tic Disorders
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Probiotic-Lactobacillus plantarum PS128

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.

• Study Type: Interventional
• Enrollment (Anticipated): 500
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Wang-Tso Lee, MD,PhD; Phone Number: 71618 +886-223123456; Email: leeped@hotmail.com
• Study Contact Backup: Name: Lee Chin Wong, MD; Phone Number: 71618 +886-223123456; Email: leechinx@hotmail.com

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • Recruiting
    • National Taiwan University Children Hospital
    • Contact: Wang-Tso Lee, PhD; Phone Number: 71618 02-23123456; Email: leeped@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 50 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo (for tic disorder); 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; placebo , 1 tablet , twice a day , 12 hrs apart, lasting 2 months for Tic disorders and 4 months for Rett syndrome
Active Comparator: PS128 (tic disorder); 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; 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; Other Names: Lactobacillus plantarum PS128
Placebo Comparator: Placebo (for Rett syndrome); 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; placebo , 1 tablet , twice a day , 12 hrs apart, lasting 2 months for Tic disorders and 4 months for Rett syndrome
Active Comparator: PS128 (Rett syndrome); 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; 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; 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

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Wang-Tso Lee, MD,PhD, National Taiwan University Children Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2017
• Primary Completion (Anticipated): August 20, 2021
• Study Completion (Anticipated): August 20, 2021

Study Registration Dates

• First Submitted: August 16, 2017
• First Submitted That Met QC Criteria: August 21, 2017
• First Posted (Actual): August 24, 2017

Study Record Updates

• Last Update Posted (Actual): October 22, 2020
• Last Update Submitted That Met QC Criteria: October 18, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Probiotic; Rett syndrome; Tourette syndrome
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Basal Ganglia Diseases; Neurodegenerative Diseases; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Neurodevelopmental Disorders; Syndrome; Movement Disorders; Rett Syndrome; Tourette Syndrome; Tic Disorders
• Other Study ID Numbers: 201703061MIPA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No