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

Phase 2

• Conditions: Dementia, Alzheimer Type

• Registration Number: NCT00154635
• Lead Sponsor: National Taiwan University Hospital

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.

Study Timeline

• Status Verified: 2005-09
• Study Start: 2005-09
• Study First Submitted: 2005-09-08
• Study First Submitted QC: 2005-09-08
• Last Update Submitted: 2005-09-08
• Study First Posted: 2005-09-12
• Last Update Posted: 2005-09-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1. Male or post menopausal female patients aged ≧50 years old;
2. The informed consent must be signed by the patient and co-signed by their proxy or principal caregivers before undergoing any study procedures;
3. Probable Alzheimer's disease based on the National Institute of Neurological and Communicative Disorders and Alzheimer's dementia and related disorder (NINCDS-ADRDA)
4. Patients with Mini-Mental State Examination (MMSE) scores of 12~24
5. Patients with Clinical Dementia Rating (CDR)in mild (CDR = 1) and moderate (CDR = 2) AD
6. Cranial computed tomography (CT) or brain magnetic resonance imaging (MRI) must be within the past 12 months;
7. Patients must be able to complete baseline assessments;
8. An eligible principal caregiver must be able to accompany the patient to all scheduled visits;
9. 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

1. 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;
2. 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;
3. 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;
4. Patients with concurrent psychosis or mood disorder (Hamilton depression scale score > 17);
5. Patients diagnosed cancer and treated within the past two years (except for non-invasive skin cancer);
6. 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;
7. Patients currently treated with any prohibited medications (listed in Concomitant Treatment section) are not able to fulfill the 2 week-washout period;
8. Participation in another study within the last 30 days;
9. Females who are within two years of their menopause unless proved not pregnant (determined by urine test);
10. Dementia caused by other etiology as indicated by clinically significant abnormal Vit B12, folic acid, or thyroid function tests.
11. Patients with neurosyphilis confirmed by CSF STS/TPHA;
12. The neuroimage CT or MRI could not be compatible with the diagnosis of probable AD as stated in the NINCDS criteria;
13. Patients with a Hachinski score (Appendix 5) above 3 are excluded.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
ADAS-Cog

Secondary Outcome Measures

Name	Time	Method
CIBIC-PLUS
IADL
Behav-AD
MMSE
CDR

Trial Locations

Locations (2)

VGH; 🇨🇳 Taipei, Taiwan

NTUH; 🇨🇳 Taipei, Taiwan