Ginkgo Biloba Prevention Trial in Older Individuals

Study Overview
=================
Brief Summary
-----------------
This study will determine the effect of 240mg/day Ginkgo biloba in decreasing the incidence of dementia and specifically Alzheimer's disease (AD), slowing cognitive decline and functional disability, reducing incidence of cardiovascular disease, and decreasing total mortality.

Detailed Description
-----------------
Participants will be studied in a randomized trial of 240 mg of Ginkgo biloba as compared to placebo in healthy men and women, at least 75 years old. The trial will last approximately 8 years. The intervention will be considered unsuccessful in those participants who succumb to dementia, including Alzheimer's Disease and vascular dementia. There are four clinical centers: Pittsburgh, PA; Hagerstown, MD; Winston-Salem, NC; and Sacramento, CA; and a Coordinating Center at the University of Washington, Seattle. There will be a clinic visit every 6 months to determine morbidity, mortality and change in cognition that will include repeat of ADAS, CDR, and 10 battery neuropsychological evaluation and informant interview. The primary endpoint is dementia, specifically Alzheimer's disease, secondary endpoint will include the incidence of vascular disease, changes in cognitive function scores over time, total mortality and changes in functional status. The diagnosis of dementia will be based on neuropsychological testing, neurological exam, MRI, functional measurements, and review by a central adjudication committee and classified by DSM IV, NINCDS criteria and ADRTC criteria for vascular disease.

Official Title
-----------------
Ginkgo Biloba Prevention Trial in Older Individuals

Conditions
-----------------
Dementia, Alzheimer's Disease

Intervention / Treatment
-----------------
* Drug: Ginkgo biloba
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Non-demented participants Willing to participate in a seven-year follow-up trial of Ginkgo Biloba English is their usual language Willing informant who has frequent contact with the participant Exclusion Criteria: Currently on anticoagulant therapy Cancer diagnosed and treated within the past two years (except for skin cancer) Participant with class III - IV congestive heart failure Currently being treated with psychopharmacological drugs for depression Hospitalized for depression within the last year Taking Aricept (or similar agents) for cognitive problems or dementia Baseline blood creatinine >2 Baseline SGGT is a marker of liver function (3 x normal>or=90 IU) Baseline hematocrit<30 Baseline white blood count>or=15,000

Ages Eligible for Study
-----------------
Minimum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo 1 pill twice a day | Drug: Placebo<br>* One pill twice daily<br>* Other names: Identical appearance as Ginkgo biloba pill;|
| Active Comparator: Ginkgo biloba<br>Ginkgo biloba EGb761 120 mg twice daily | Drug: Ginkgo biloba<br>* 120mg twice a day<br>* Other names: EGb761;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Incident Dementia | All cause dementia based on DSM-IV criteria as determined by an expert panel of clinicians using an adjudication process. A full neuropsychological battery was administered annually, or at 6 month visit if there was a diagnosis of dementia or initiation of medication for dementia by private physician, or change in Modified Mini Mental State Exam (3MSE), Clinical Dementia Rating (CDR), or Alzheimer Disease Assessment Scale (ADAS-Cog). Decline on tests scores based on an algorithm resulted in a neurological exam and brain imaging. These data were used in the adjudication process. | Brief neuropsychological testing every 6 months, detailed testing annually, average 6.1 years follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With the Indicated Cardiovascular Disease or Mortality | Myocardial infarction (MI), angina, stroke (CVA), transient ischemic attack (TIA), combined coronary heart disease (CHD) (MI/angina), combined cerebrovascular (CVA/TIA), peripheral vascular disease, and mortality | 6 months | 
| Progression of Cognitive Decline in Standardized Z-score Scale. Higher Z-scores Indicate Worse Performance. | Rate of annual change by cognitive domain in standardized Z-score scale. Higher Z-scores indicate worse performance. Best score = -2.0 Z-score change per year (improvement); worse score = 2.0 Z-score change per year (decline). | 6 months/annually |