The Efficacy of Traditional Chinese Herbal Medicine for Alzheimer's Disease

Study Overview
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Brief Summary
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This randomized, double-blinded, placebo-controlled, crossover clinical trial aims to investigate the effect of VGH-AD1, a scientific Chinese medicine powder prescription, on patients with Alzheimer's disease.

Detailed Description
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Dementia is a chronic, progressive neurodegenerative syndrome, characterized by an abroad category of non-reversible impairment in cerebral function, making a long-term and gradual decrease in the ability to mental cognitive tasks and performance of daily activities. The World Health Organization says that 47.5 million people around the world are living with dementia. Alzheimer's disease is accounting for 60-70 percent, the most common type of dementia. According to the record from the Ministry of Health and welfare in Taiwan, the population over 65-year-old is more than 3.36 million. It is estimated that there are more than 250,000 people with mental disabilities and nearly 600,000 people with mild cognitive impairment. With the aging of the population, experts predict that the number of patients suffering from Alzheimer's disease will be up to 800,000. In 2016, a study based on the health insurance database from 1997 to 2008 in Taiwan showed that 78.2 percent of patients have received Chinese medicine treatment, such as herbal medicine and acupuncture after diagnosed as Alzheimer's disease. Therefore, this clinical trial is designed as a randomized, double-blinded, placebo-controlled, crossover clinical trial that aims to investigate the effect of VGH-AD1, traditional Chinese herbal medicine powder, on Alzheimer's disease. Participants will be randomized allocated 14 participants into each group A and B. Group A will receive VGH-AD1, while group B will receive a placebo two times per day for eight weeks. Then entry two weeks wash-out period. And then two groups will be switched for another eight weeks. Post-study follow up will be 4 weeks after the intervention end. The study duration is totally 22 weeks. All participants will be assessed by the MMSE, IADL, NPI-Q, IQCODE, GDS, QOL-AD, TCM50, which will be conducted at baseline, week 8,10,18 and 22.

Official Title
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The Effect of Traditional Chinese Medicine (VGH-AD1) on Patients With Alzheimer's Disease: A Double-blinded Randomized Placebo-controlled Cross-over Study

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: VGH-AD1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged over 65 years old regardless of gender. Under the subject's and caregiver's willing and agreement. According to DSM5 (American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing), was diagnosis of mild to moderate Alzheimer's type dementia; MMSE score between 14 and 26; Under standard treatment regularly over 3 months. (Includes Acetylcholinesterase inhibitor, NMDA receptor antagonist, and antipsychotics, antidepressants, mood stabilizer, and anxiolytic agents) Exclusion Criteria: Other types of dementia, such as Frontotemporal dementia, Dementia with Lewy Bodies, Vascular Dementia, and mixed type, et al; Known of other neurological diseases, cranial nervous system cancer Severe liver or kidney dysfunction (alanine aminotransferase>200 IU/L, aspartate transaminase>200 IU/L or serum creatinine >2.5 mg/dl); Severe cardiovascular disease (heart failure, coronary heart disease

Ages Eligible for Study
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Minimum Age: 65 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: Crossover Assignment
Interventional Model Description: 28 participants will be recruited from the Division of Psychiatry and Neurology in a Medical Center. They will be randomized allocated into treatment and control groups, each including 14 participants. After eight weeks of taking, there is two-weeks of wash-out period. And then two groups will be switched for another eight weeks. Post-study follow up will be 4 weeks later once the intervention end. The study duration is totally 22 weeks.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Group A will receive VGH-AD1 two times per day for 8 weeks, then entry 2 weeks wash-out period. Then switch to receive the placebo for another 8 weeks. Post-follow up will be 4 weeks later. | Drug: VGH-AD1<br>* VGH-AD1 includes Yi-gan-san 3.0g, Huan-shao-dan 1.0g, Danshen(Radix et Rhizoma Salviae Miltiorrhizae) 0.75g, Tian-ma(Rhizoma Gastrodiae) 0.75g, Gou-teng(Ramulus Uncariae Cum Uneis) 0.375g, and Ba-ji-tian(Radix Morindae Officinalis) 0.375g, two times per day, each serving a small packet of 7.5 grams of concentrated granules.<br>|
| Placebo Comparator: Group B<br>Group B will receive placebo two times per day for 8 weeks, then entry 2 weeks wash-out period. Then switch to receive the VGH-AD1 for another 8 weeks. Post-follow up will be 4 weeks later. | Drug: VGH-AD1<br>* VGH-AD1 includes Yi-gan-san 3.0g, Huan-shao-dan 1.0g, Danshen(Radix et Rhizoma Salviae Miltiorrhizae) 0.75g, Tian-ma(Rhizoma Gastrodiae) 0.75g, Gou-teng(Ramulus Uncariae Cum Uneis) 0.375g, and Ba-ji-tian(Radix Morindae Officinalis) 0.375g, two times per day, each serving a small packet of 7.5 grams of concentrated granules.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of Geriatric Depression Scale (GDS) | The Geriatric Depression Scale (GDS) is a 30-item self-report assessment used to identify depression in the elderly, which will be conducted at baseline, week8, 10,18 and follow-up (22 weeks). | week 0, 8, 10,18,22 | 
| Changes of Mini-Mental State Examination (MMSE) | Global cognition will be assessed by the MMSE,which will be conducted at baseline, week8, 10,18 and follow-up (22 weeks). | week 0, 8, 10,18,22 | 
| Changes of Neuropsychiatric Inventory(NPI-Q) | The Neuropsychiatric Inventory Questionnaire (NPI-Q) is an informant-based instrument that measures the presence and severity of 12 Neuropsychiatric Symptoms (NPS) in patients with dementia, as well as informant distress. The NPIQ will be conducted at baseline, week 8, 10,18 and follow-up (22 weeks). | week 0, 8, 10,18,22 | 
| Changes of Instrumental Activities of Daily Living (IADL) | The instrumental activities of daily living (IADL) contains 8 items, such as shopping, cooking, doing laundry, handling finances, using telephone, mode of transportation, responsibility for own medication and housekeeping. The IADL will be conducted baseline, week 8, 10,18 and follow-up (22 weeks). | week 0, 8, 10,18,22 | 
| 5. Changes of The Informant Questionnaire on Cognitive Decline in the Elderly (Short-IQCODE) | The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) provides ratings of an individual's changes in everyday cognitive functions during the previous 10 years. The questionnaire contains a total 26 questions with scores 0 to 5. The item includes short-term memory, living skills, writing, house chores, and financial dealing. If the performance remains the same as 10 years ago, then rate 3. If the performance is much worsened compare 10 years ago, then rate 5; oppositely rate 1. | week 0, 8, 10,18,22 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of Quality of Life-Alzheimer's Disease (QOL-AD) | The Quality of Life-Alzheimer's Disease (QOL-AD) has 13-items covering physical health, energy, mood, living situations, memory, family, marriage, friends, chores, fun, money, self and life as a whole. The QOL-AD uses straightforward language for simplicity, which will be conducted at baseline, 8, 10,18 and follow-up (22 weeks). | week 0, 8, 10,18,22 | 
| Changes of Constitution in Chinese Medicine Questionnaire (TCM50) | The Constitution in Chinese Medicine Questionnaire (TCM50) consists of 60 items to classify a person into one or more of nine Body constitution(BC) types: gentleness (8 Items), Qi-deficiency (8 Items), Yang-deficiency (7 Items), Yin-deficiency (8 Items), phlegm-wetness (8 Items), wetness-heat (6 Items), blood-stasis (7 Items), Qi-depression (7 Items), and special diathesis (7 Items). Coexistence of multiple imbalanced BC types was possible which is consistent with the TCM theories. The scoring algorithm proposed in the original CCMQ was adopted in this study. A higher score in the CCMQ BC scale indicates a higher likelihood of the specific BC type, and a score of 30 is set as threshold for case definition. The CCMQ will be conducted at baseline, 8, 10,18 and follow-up (22 weeks). | week 0, 8, 10,18,22 | 
| Chinese medicine adverse effect assessment | In order to cautiously evaluate and monitor the safety of Chinese medicine, the adverse effect assessment form should be filled each time the subject visits. | week 0, 4, 8, 10, 14, 18, 22 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chinese Herbal Medicine, Alzheimer's disease, Complementary Medicine