Chinese Herbal Medicine Treatment as Adjunct Therapy for Parkinson's Disease

Study Overview
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Brief Summary
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Background: Parkinson's disease (PD) is a prevalent and debilitating condition. Conventional medications cannot control all symptoms and may inflict adverse effects. A survey reported that Chinese herbal medicine (CHM) is frequently sought. Existing CHM trials were contradictory and often of poor quality due to a lack of methodological rigor. A national clinical guideline was drafted in China with diagnostic criteria and treatment strategy of Chinese medicine (CM) patterns subgroups of PD. The suggested CHM was found to exhibit a neuroprotective effect in in vitro and in vivo studies. This trial aims to preliminarily assess the effect of CHM prescribed based on pattern differentiation on PD symptoms and patients' quality of life, and evaluate the feasibility of the trial design for a future large-scale trial. Methods: This trial will be a pilot assessor- and data analyst blind, add-on, randomised, controlled, pragmatic clinical trial. 160 PD patients will be recruited and randomised into treatment or control groups in a 1:1 ratio. The trial will be conducted over 32 weeks. PD patients in the treatment group will be stratified into subgroups based on CM pattern and receive CHM accordingly in addition to conventional medication (ConM). The control group will receive ConM only. The primary outcome will be part II of the Movement Disorder Society Sponsored Revision of Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Secondary outcomes will include part and total scores of MDS-UPDRS, domain and total scores of Non-motor symptom scale (NMSS). Adverse events will be monitored by monthly follow-ups and questionnaires. Mixed models will be used to analyse data by Jamovi and R. Expected outcomes: The success of our trial will show that the pragmatic design with subgroup differentiation is feasible and can produce reliable results. It will also provide preliminary data of the effect of CHM on improving clinical outcomes and quality of PD patients. Data collected will be used to optimize the study design of the future large-scale clinical study. Ethical clearance: Ethical clearance of this study was given by the Research Ethics Committee of Hong Kong Baptist University (REC/20-21/0206).

Official Title
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Chinese Herbal Medicine Treatment Based on Subgroup Differentiation as Adjunct Therapy for Parkinson's Disease: a Pilot add-on, Randomised, Controlled, Pragmatic Clinical Trial

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: Conventional medication
* Drug: Chinese herbal medicine treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosed with PD according to United Kingdom Parkinson's Disease Society Brain Bank (UKPDBB) diagnostic criteria aged 18 to 80 years old under stable ConM treatment with no alteration of dosage in the past 30 days Exclusion Criteria: secondary PD or atypical parkinsonian disorder used antidepressants in the previous month with concurrent psychiatric, mood, or other neurological disorders suicidal (with suicidal thoughts in the past year) with concurrent severe disorders, such as cancer and myocardial infarction participation in another Chinese herbal medicine clinical study pregnant or breast-feeding Hoehn and Yahr (H&Y) stage 4 or above liver and renal function derangement

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chinese herbal medicine treatment plus conventional medication<br>Participants will receive integrated medicine treatment combining Chinese herbal treatment, given in the form of granules, and conventional medication for 32 weeks. Patients will be differentiated into 4 subgroups based on their Chinese medicine pattern, and receive herbal treatment accordingly. An existing clinical pathway will guide the diagnosis and treatment of the Chinese medicine patterns. The four pattern subgroups are as follows: 1) the Phlegm-heat stirring Wind subgroup; 2) the Spleen-and Kidney-Yang subgroup; 3) the Internal Stirring of Yang and Wind subgroup; and 4) the Qi deficiency and stasis of Blood subgroup To resemble actual clinical practice, minor adjustment of herbal treatment will be possible and also adhere to the mentioned clinical guideline. The dosage of each herbal drug will follow the instructions of China Pharmacopeia. | Drug: Conventional medication<br>* Levodopa, dopamine agonist, Monoamine oxidase-B inhibitors, Catechol-O-methyltransferase inhibitors, etc.<br>Drug: Chinese herbal medicine treatment<br>* Huanglian Wendan Decoction Jin Gui Shen Qi Pill Liu Wei Di Huang Pill plus Tian Ma Gou Teng Decoction Bu Yang Huan Wu Decoction<br>|
| Active Comparator: Conventional medication<br>Conventional medication for Parkinson's disease include levodopa, dopamine agonist, Monoamine oxidase-B inhibitors, Catechol-O-methyltransferase inhibitors, etc. | Drug: Conventional medication<br>* Levodopa, dopamine agonist, Monoamine oxidase-B inhibitors, Catechol-O-methyltransferase inhibitors, etc.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the Movement Disorder Society Sponsored Revision of Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II | Assesses the self-reported motor experience of the daily living of Parkinson's patients Scale (Higher the score, the more severe the condition or symptom): 0: Normal, 1: Slight, 2: Mild, 3: Moderate, 4: Severe | from baseline to week 32 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part I, III and IV as well as the total score of MDS-UPDRS | Comprehensively assesses motor, non motor, and motor complications of Parkinson's patients Scale (Higher the score, the more severe the condition or symptom): Scale: 0: Normal, 1: Slight, 2: Mild, 3: Moderate, 4: Severe | from baseline to week 32 | 
| Non-motor symptom scale | Assesses in details the severity of non motor symptoms of Parkinson's Scale (Higher the score, the more severe the condition or symptom): Severity: 0 = None, 1= Mild (symptoms present but causes little distress or disturbance to patient), 2 = Moderate (some distress or disturbance to patient), 3 = Severe (major source of distress or disturbance to patient); Frequency: 1 = Rarely (<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) | from baseline to week 32 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chinese medicine, Pragmatic trial, MDS-UPDRS