Efficacy of Probiotics for Parkinson Disease (PD)

Study Overview
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Brief Summary
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In previous clinical studies, PS128 has been reported to ameliorate motor deficits in Parkinson's disease (PD). PS23 has been reported to delay some age-related disorders. On the basis of previous animal and clinical studies which hope that this study can support the theory of the gut-brain axis, and have the opportunity to realize the relationship between peripheral inflammation and neurodegeneration.

Detailed Description
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The gut microbiota plays important roles in gastrointestinal homeostasis, essential physiological processes and CNS function, and affects the gut-brain axis via neural, immune and endocrine pathways giving rise to the microbiota-gut-brain-axis (MGBA). Combining the MGBA concept and the theory that Parkinson's disease (PD) is derived in the gut, researchers have studied the relationship between the gut microbiota and the PD neurodegenerative process. Probiotics are live microorganisms that confer health benefits on the host and can improve host physical and mental health by affecting MGBA homeostasis. Lactobacillus plantarum PS128 (PS128) and Lactobacillus paracasei PS23 (PS23) are specific probiotics, known as a psychobiotic, which has been demonstrated to alleviate depression- and anxiety-like behaviors in mouse model. Furthermore, PS128 alleviated motor deficits, nigrostriatal dopaminergic neuronal cell death, and striatal dopamine reduction in the MPTP mouse model of Parkinson's disease. In previous clinical studies, PS128 has been reported to ameliorate motor deficits in PD. PS23 has been reported to delay some age-related disorders. On the basis of previous animal and clinical studies which hope that this study can support the theory of the gut-brain axis, and have the opportunity to realize the relationship between peripheral inflammation and neurodegeneration. The eligible participants will be administered with probiotics capsules for 12 weeks. Symptoms of PD will be clinically evaluated before and after the treatment. Blood and stool samples will be collected before and after the intervention for biochemical parameters.

Official Title
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Efficacy of Probiotics for Parkinson Disease (PD)

Conditions
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Parkinson's Disease (PD), Movement Disorders, Depression, Anxiety

Intervention / Treatment
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* Dietary Supplement: probiotics
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The age between 41-80 years old and at least the elementary education level. Diagnosed as a patient with Parkinson's disease of modified Hoehn and Yahr Stage between 1 and 3 as rated. Exclusion Criteria: Diagnosed before 40 years old. Used probiotic products in powder, capsule, or tablet form within four weeks. Have taken antibiotics within four weeks. Those who are not suitable to participate in the research are judged by PI.

Ages Eligible for Study
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Minimum Age: 41 Years
Maximum Age: 80 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 300 Participants are assigned to the probiotics and a placebo group, under the double-blind trial.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotics<br>daily ingestion of 2 capsules of probiotics (>30 billion CFU/capsule) | Dietary Supplement: probiotics<br>* >30 billion CFU/capsule<br>|
| Placebo Comparator: Placebo<br>daily ingestion of 2 capsules which only contained 425 ± 25 mg microcrystalline cellulose | Dietary Supplement: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| UPDRS III | The UPDRS scale refers to Unified Parkinson Disease Rating Scale, and it is a rating tool used to gauge the course of Parkinson's disease in patients. The PART III is Motor sections. | From Baseline to 12 Weeks Assessed | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impression scales of Severity rated by clinician（CGI） | The CGIC is a single-item questionnaire that asks the investigator to assess a patient's PD symptoms at specific visits after initiating therapy. The CGIC uses a 7 point Likert Scale, ranging from very much worse (-3) to very much improved (+3), to assess overall response to therapy. A treatment success was defined as much improved or very much improved at the week 12 visit. | From Baseline to 12 Weeks Assessed | 
| UPDRS I-IV | The UPDRS scale refers to Unified Parkinson Disease Rating Scale, and it is a rating tool used to gauge the course of Parkinson's disease in patients.Scale UPDRS the sum of parts I, II and III ranges from 0 to 176. The UPDRS score has three components, each consisting of questions with 0-4 point scale. Part I assesses mentation, behavior, and mood; Part II assesses activities of daily; and Part III assesses motor abilities. Where 0 represents the absence of impairment and 4 represents the highest degree of impairment. | From Baseline to 12 Weeks Assessed | 
| Q-LES-Q | Participants who receive app-CBT will have greater improvement on quality of life, assessed using The Quality of Life, Enjoyment, and Satisfaction Questionnaire - Short Form (Q-LES-Q). The Q-LES-Q-SF is a self-report measure of subjective quality of life, containing Likert items ranging from 1 (Very Poor) to 5 (Very Good). Total scores are presented as a percentage of the maximum value (i.e., ranging from 0 to 100, with higher scores indicating greater quality of life). | From Baseline to 12 Weeks Assessed | 
| Visual Analogue Scale for GI symptoms, VAS-GI | Visual Analogue Scale for GI symptoms, VAS-GI (visual analogue scale, VAS 0-10) was designed to measure the response of symptoms and well-being in patients after taking probiotics | From Baseline to 12 Weeks Assessed | 
| PGI-C | The PGIC is a scale participants use to rate the level of change they have experienced following treatment. The PGIC is a 7-point scale from 1 (very much better) to 7 (very much worse). | From Baseline to 12 Weeks Assessed | 
| PHQ-9 | Measure for Major Depressive Disorder from questionnaire responses, to measure the prevalence of clinically significant depression defined as a PHQ-9 score of equal to or greater than 10. | From Baseline to 12 Weeks Assessed | 
| Differences in the State and Trait Anxiety Index (STAI) | The State-Trait Anxiety Inventory (STAI) is a commonly used measure of trait and state anxiety. All items are rated on a 4-point scale (e.g., from Almost Never to Almost Always). Higher scores indicate greater anxiety. | From Baseline to 12 Weeks Assessed | 
| Difference in Oxidative stress - blood level of HSCRP | To assess inflammation indicators, used commercial kit human CRP (Cayman, Mich, USA) and Elisa reader (PerkinElmer, Massachusetts, USA) for analysis | From Baseline to 12 Weeks Assessed | 
| Gut microbiota | Collect the DNA of fecal flora to test the diversity and abundance of gut microbiota in Stool samples before and after probiotics | From Baseline to 12 Weeks Assessed | 
| Level of Growth Differentiation Factor-15 | Level of Growth Differentiation Factor-15 | From Baseline to 12 Weeks Assessed | 
| brain-derived neurotropic factor (BDNF) | Measurement BDNF level in serum | From Baseline to 12 Weeks Assessed |