Efficacy and Safety Study of DCB-AD1 in Patients With Mild to Moderate Alzheimer's Disease

Study Overview
=================
Brief Summary
-----------------
A Double-blind, Randomized, Placebo Controlled Study to Evaluate the Efficacy and Safety of DCB-AD1 in Patients with Mild to Moderate Alzheimer's Disease. Because of the limitation of the sample size we could expect but a positive trend of the efficacy unless the effect size of DCB-AD1 is larger than 0.63. This information will provide us clue if further clinical investigation such as a phase III study should be carried out in an even larger scale. We also should be able to obtain valuable experience on the adverse effect of prolonged (24-week) use of Fo-ti.

Detailed Description
-----------------
The growing number of patients with dementia has become a great concern of many aging societies. Up to this moment no treatment can stop Alzheimer's dementia (AD), thus, developing new treatments are still mandatory. In this study we will investigate a new drug DCB-AD1, an herbal medicine derived from root of Fo-ti. Historically the Chinese used the Fo-ti root for its rejuvenating properties to treat premature aging, weakness and so on. In DCB (Development Center of Biotechnology)'s preliminary studies using human neuroblastoma cell, SK-N-SH, Fo-ti water extracts exhibited high potential in preventing A-beta and hydrogen peroxide-induced cell death. From two different AD animal models, DCB have observed neuroprotection effects of Fo-ti using water maze and hole-board exploration tests, Though the pharmacological effect of Fo-ti has yet been clarified, its protective effect may result from radical scavenging activities, anti-inflammatory effect or anti-peroxidation. We intend to investigate DCB-AD1 on its cognitive and neurophysiological effects on Alzheimer disease through a randomized, double-blind, placebo-controlled therapeutic trial for 24 weeks. We will complete 80 eligible cases for analysis in this clinical trial with 40 in each investigation site. The estimated drop-out rate is around 25 30 %. Patients are eligible if they fulfill criteria for a diagnosis of probable AD of NINCDS-ADRDA. We will include patients with Mini-Mental State Examination scores of 12 24 and Clinical Dementia Rating 1 or 2. Patients will be allowed to take cholinesterase inhibitors, donepezil, rivastigmine, galantamine or memantine if the dose has been unchanged for the last 3 months before the study entry and remains stable during the 24-week study period. As for the outcome measures, the primary end point will be the score changes of ADAS-Cog at the end of treatment from the baseline. Secondary end points include CIBIC-PLUS, IADL, Behav-AD, MMSE and CDR. The statistic analysis will be on both intention-to-treat and completed cases. Because of the limitation of the sample size we would expect but a positive trend of the efficacy unless the effect size of DCB-AD1 is larger than 0.63. This information will provide us clue if further clinical investigation such as a phase III study should be carried out in an even larger scale. We will valuable experience on the adverse effect of prolonged (24-week) use of Fo-ti.

Official Title
-----------------
A Double-Blind, Randomized, Placebo Controlled Study to Evaluate the Efficacy and Safety of DCB-AD1 in Patients With Mild to Moderate Alzheimer's Disease

Conditions
-----------------
Dementia, Alzheimer Type

Intervention / Treatment
-----------------
* Drug: DCB-AD1


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or post menopausal female patients aged ≧50 years old; The informed consent must be signed by the patient and co-signed by their proxy or principal caregivers before undergoing any study procedures; Probable Alzheimer's disease based on the National Institute of Neurological and Communicative Disorders and Alzheimer's dementia and related disorder (NINCDS-ADRDA) Patients with Mini-Mental State Examination (MMSE) scores of 12 24 Patients with Clinical Dementia Rating (CDR)in mild (CDR = 1) and moderate (CDR = 2) AD Cranial computed tomography (CT) or brain magnetic resonance imaging (MRI) must be within the past 12 months; Patients must be able to complete baseline assessments; An eligible principal caregiver must be able to accompany the patient to all scheduled visits; Patients currently taking ChEIs such as donepezil, rivastigmine, or galantamine are allowed if the dose has been unchanged for the last 3 months before the study entry. Exclusion Criteria: Patients with history of severe systemic disease such as coronary artery disease, myocardial infarct, progressive heart failure, chronic obstructive pulmonary disease within the past 1 year; Patients with hepatic and renal insufficiency (ALT、AST 3 times above normal range; serum creatinine 2 times above normal range), diabetic patients with poor control of blood sugar (HbA1c>8.5) at study entry; Patients with central nervous system disease other than AD such as cerebral vascular disease, Parkinson's disease, epilepsy, traumatic brain injury, central nervous system infection, and alcoholic encephalopathy; Patients with concurrent psychosis or mood disorder (Hamilton depression scale score > 17); Patients diagnosed cancer and treated within the past two years (except for non-invasive skin cancer); Patients with general medical conditions, which may confound the results of the study, pose additional risk or preclude evaluation and assessments in this study as judged by the investigator; Patients currently treated with any prohibited medications (listed in Concomitant Treatment section) are not able to fulfill the 2 week-washout period; Participation in another study within the last 30 days; Females who are within two years of their menopause unless proved not pregnant (determined by urine test); Dementia caused by other etiology as indicated by clinically significant abnormal Vit B12, folic acid, or thyroid function tests. Patients with neurosyphilis confirmed by CSF STS/TPHA; The neuroimage CT or MRI could not be compatible with the diagnosis of probable AD as stated in the NINCDS criteria; Patients with a Hachinski score (Appendix 5) above 3 are excluded.

Ages Eligible for Study
-----------------
Minimum Age: 50 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: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: DCB-AD1|nan|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ADAS-Cog |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CIBIC-PLUS |  |  | 
| IADL |  |  | 
| Behav-AD |  |  | 
| MMSE |  |  | 
| CDR |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Fo-ti, Alzheimer's disease, Chinese herbs