Efficacy and Safety Study of Shenwu Capsule

Study Overview
=================
Brief Summary
-----------------
The purpose of this phase III study is to further evaluate the effects of shenwu capsule, a traditional Chinese herbal medicine, on cognition, function and memory in patients with amnestic mild cognitive impairment (MCI) who are at greater risk for developing Alzheimer's disease, in a 6-month supervised protocol of a traditional Chinese herbal medicine. The results of this study may provide support for a relatively simple and inexpensive treatment strategy with herbal therapy that specifically targets individuals with the mild cognitive impairment that directly influence risk of developing dementia for older adults.

Detailed Description
-----------------
Mild cognitive impairment (MCI) refers to a group of individuals who have some cognitive impairment but of insufficient severity to constitute dementia1,which is a transitional stage between normal aging and dementia. Amnestic MCI is the most common subtype of MCI, which shows the least reversion to normal, and is defined as a significant impairment in memory but with no impairment in activities of daily living. In an interventional study of patients meeting Petersen criteria for amnestic MCI, 16% progressed to dementia per year, 99% of whom received an AD diagnosis. Hence, MCI, in particular amnestic MCI is generally recognized in many cases to represent prodromal AD and becomes a new target for prevention and treatment of AD. The specific aims for the study is to evaluate change in Efficacy and safety of shenwu capsule in treating amnestic MCI. Using a randomized controlled parallel group design, 324 older adults diagnosed with amnestic MCI participate in a 6-month supervised protocol of either shenwu capsule or donepezil. Cognitive testing and blood collection will occur at baseline, and months 3 and 6. Before the 6-month intervention, medial temporal atrophy (MTA) or hippocampal volume atrophy on the CT or MRI scan are assessed for all subjects. The results of this study may provide support for a safer and inexpensive treatment strategy that specifically targets individuals with the mild cognitive impairment that directly influence risk of developing dementia for older adults.

Official Title
-----------------
Phase III Study of Shenwu Capsule in Treating Amnestic Mild Cognitive Impairment

Conditions
-----------------
Mild Cognitive Impairment

Intervention / Treatment
-----------------
* Drug: Shenwu Capsule
* Drug: Donepezil


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Chinese-speaking adults at least 55 to 80 years of age old, weighting between 45 to 90 kilograms, living in the community. diagnosed with amnestic MCI at screening: (1) memory complaint, corroborated by an informant; (2) abnormal memory function, as screened by the WMS-R Logical Memory II Delayed Story Recall subtest score <10.4 for age; (3) normal general cognitive function, as determined by a clinician's judgment based on a structured interview with the patients (MMSE of 24 to 30 score for education ); (4) no or minimal impairment in activities of daily living, as determined by a clinical interview with the patient and informant (IADL <16 score); and (5) not sufficiently impaired, cognitively and functionally, to meet NINCDS-ADRDA criteria for AD, as judged by an experienced AD research clinician. In addition, they were judged to be at stage 2-3 of the GDS, and to have a score of ≤12 of the HAMD for 17 items, of ≤4 on the HIS, and no or minimal medial temporal atrophy (MTA) or hippocampal volume atrophy on the MRI scan. The subjects required adequate vision and hearing to participate in study assessments. Patients receiving chronic aspirin therapy for cardio-protection (≤100 mg per day) or stable doses of antidepressants for at least 3 months were also eligible. Exclusion Criteria: Significant neurologic disease that might affect cognition, such as a diagnosis of Alzheimer's disease, stroke, Parkinson's disease, multiple sclerosis, or severe head injury with loss of consciousness; a score of MMSE<24,or any major psychiatric disorder (e.g., DSM-IV-defined psychosis, major depression, bipolar disorder, or alcohol or substance abuse); Recent history of chronic use of NSAIDs or aspirin (>100 mg per day); History of upper gastrointestinal bleeding that required transfusion or surgery within the previous 3 years,or documented evidence of an active gastric or duodenal ulcer within the previous 3 months,or history of NSAID-associated ulcers; History of active malignancy except for basal cell carcinoma or squamous cell carcinoma of the skin, or prostate cancer, within the preceding 24 months; A chronic or acute renal, hepatic, or metabolic disorder; and uncontrolled hypertension and diabetes mellitus; History of hypersensitivity to the treatment drugs; or concomitant drugs (including anticonvulsant agents, anti-parkinsonian agents, antipsychotics, anxiolytics, hypnotic agents, neuroleptic agents, cholinomimetic agents, vitamin E, or ginkgo biloba extract or any other drugs including traditional Chinese herbal medicines which can affect memory); or participants in other clinical studies within the past 30 days.

Ages Eligible for Study
-----------------
Minimum Age: 55 Years
Maximum Age: 80 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 |
| --- | --- |
| Experimental: Shenwu Capsule<br>Shenwu Capsule:1 capsule contains 451 mg of Shenwu extracts. 5 capsules/time, 3 times/day for 6 months. Placebo: Placebo identical to donepezil tablets,1 placebo tablet/time, 1 time/day for 6 months. | Drug: Shenwu Capsule<br>* 1 shenwu capsule contains 451 mg extract from herbs.5 capsules/time, 3 times/day for 6 months. Placebo identified to donepezil: 1 tablet per time, 1 time per day for 6 months.<br>* Other names: Shenwu;|
| Active Comparator: Donepezil<br>Donepezil: 1 tablet contains 5 mg of donepezil, 1 tablet/time, 1time/day for 6 months. Placebo: Placebo identical to shenwu capsules,5 placebo capsules/time,3 times/day for 6 months | Drug: Donepezil<br>* This active drug is donepezil 5 mg tablet. 1 tablet/time, 1 time/day for 6 months. Placebo identical to shenwu capsules,5 capsules/time,3times/day for 6months.<br>* Other names: Aricept;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cognitive Scores: Alzheimer Disease Assessment Scale-cognitive. Subscale (ADAS-cog) | Cognition was assessed with the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) , at baseline (day 1 clinic visit) and at 12-week intervals thereafter until week 24. The ADAS-cog was designed specifically to evaluate the severity of cognitive dysfunctions characteristic of AD patients and includes 11 items. Among these items, memory, orientation, language function, practical ability, and attention are evaluated. The score on the ADAS-cog range from 0 to 70 point, with 0 point indicating no impairment and 70 points indicating severe impairment of cognition. In the Shenwu capsule group, the ADAS-cog score is ranges 3-38.3 points, and 3.3-30.7 points in the Donepezil group. The Change in cognitive scores was calculated as24 week minus the baseline. | baseline and 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Memory Scores: The Delayed Story Recall (DSR) Test From the Adult Memory and Information Processing Battery (AMIPB) | memory function was evaluated with the DSR subtest,at baseline (day 1 clinic visit), at the mid-study (week 12), and at the endpoint of treatment (week 24). The DSR is a tool which was designed to assess immediate registration of verbal information and retention over time. It contains six sub-tests: two verbal memory tests (one of which is a story recall), two visual memory tests and two information-processing tests. The story recall test includes immediate story recall (ISR) and delayed story recall (DSR). The DSR total score ranges from 0-56 points. Lowers score means higher impairment of memory.The Change in cognitive scores was calculated as 24 week minus the baseline. | Baseline and 24 weeks | 
| Change in Functional Scores: Instrumental Activities of Daily Living (IADL). | Functional ability was evaluated with the Instrumental Activities of Daily Living (IADL) IADL, at baseline (day 1 clinic visit), at the mid-study (week 12), and at the endpoint of treatment (week 24). The IADL contains eight items, which are the ability to use a telephone, shop, prepare food, run laundry, use modes of transportation, take responsibility for one's own medications, complete housekeeping, and handle finances,each items ranges from 1 to 4 points, 1 points means no problem, and 4 points means greater impairment in instumental acvtiveity of daily living.The total is sub of the eight items, and the total range of the IADL is 8-32 points, higher scores indicate greater impairments. The changes was calculted by weeks 24 minus baseline. | Baseline to weeks 24 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Mild cognitive impairment