Trial Outcomes & Findings for Ginkgo Biloba Prevention Trial in Older Individuals (NCT NCT00010803)

Last Updated: 2013-03-14

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

3069 participants

Primary outcome timeframe

Brief neuropsychological testing every 6 months, detailed testing annually, average 6.1 years follow up

Results posted on

2013-03-14

Participant Flow

Recruitment occured between September 2000 through June 2002 primarily using mass mailings from targeted lists such as voter's registration and commercially available lists. Some sites chose to supplement this approach with newspaper, radio and television ads plus newsletter articles, posters and community presentations.

After mailing brochures to potential participants, we conducted a telephone screening followed by an in-person clinic visit to finalize eligibility. Randomization was done at a second visit within close proximity to the screening visit.

Participant milestones

Participant milestones
Measure	Ginkgo Biloba EGb 761 Ginkgo biloba 120 mg twice daily	Placebo Placebo twice daily
Overall Study STARTED	1545	1524
Overall Study COMPLETED	1448	1426
Overall Study NOT COMPLETED	97	98

Reasons for withdrawal

Reasons for withdrawal
Measure	Ginkgo Biloba EGb 761 Ginkgo biloba 120 mg twice daily	Placebo Placebo twice daily
Overall Study Withdrawal by Subject	97	98

Baseline Characteristics

Ginkgo Biloba Prevention Trial in Older Individuals

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ginkgo Biloba n=1545 Participants 120 mg twice daily, total 240 mg	Placebo n=1524 Participants Placebo 1 pill twice daily	Total n=3069 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	1545 Participants n=5 Participants	1524 Participants n=7 Participants	3069 Participants n=5 Participants
Age Continuous	79.1 years STANDARD_DEVIATION 3.3 • n=5 Participants	79.1 years STANDARD_DEVIATION 3.3 • n=7 Participants	79.1 years STANDARD_DEVIATION 3.3 • n=5 Participants
Sex: Female, Male Female	702 Participants n=5 Participants	716 Participants n=7 Participants	1418 Participants n=5 Participants
Sex: Female, Male Male	843 Participants n=5 Participants	808 Participants n=7 Participants	1651 Participants n=5 Participants
Region of Enrollment United States	1545 participants n=5 Participants	1524 participants n=7 Participants	3069 participants n=5 Participants

PRIMARY outcome

Timeframe: Brief neuropsychological testing every 6 months, detailed testing annually, average 6.1 years follow up

Population: Subjects developing incident dementia during trial in each group, intention to treat (ITT).

Outcome measures

Outcome measures
Measure	Ginkgo Biloba n=1545 Participants 120 mg twice daily, total 240 mg	Placebo n=1524 Participants Placebo 1 pill twice a day
Number of Participants With Incident Dementia	277 Participants	246 Participants

SECONDARY outcome

Timeframe: 6 months

Population: Total cohort of 3069 based on same design as primary outcome, ITT.

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

Outcome measures

Outcome measures
Measure	Ginkgo Biloba n=1545 Participants 120 mg twice daily, total 240 mg	Placebo n=1524 Participants Placebo 1 pill twice a day
Number of Participants With the Indicated Cardiovascular Disease or Mortality Total Mortality	197 Participants	188 Participants
Number of Participants With the Indicated Cardiovascular Disease or Mortality Atherosclerotic CHD Mortality	45 Participants	42 Participants
Number of Participants With the Indicated Cardiovascular Disease or Mortality Incident MI	68 Participants	60 Participants
Number of Participants With the Indicated Cardiovascular Disease or Mortality Incident Angina	66 Participants	76 Participants
Number of Participants With the Indicated Cardiovascular Disease or Mortality Incident CHD (MI &/or angina)	107 Participants	110 Participants
Number of Participants With the Indicated Cardiovascular Disease or Mortality Incident CHF	112 Participants	122 Participants
Number of Participants With the Indicated Cardiovascular Disease or Mortality Incident Stroke	73 Participants	59 Participants
Number of Participants With the Indicated Cardiovascular Disease or Mortality Incident TIA	27 Participants	31 Participants
Number of Participants With the Indicated Cardiovascular Disease or Mortality Incident CVD (stroke &/or TIA)	99 Participants	88 Participants
Number of Participants With the Indicated Cardiovascular Disease or Mortality Total CHD and CVD	157 Participants	154 Participants

SECONDARY outcome

Timeframe: 6 months/annually

Population: Final test scores were imputed for participants who did not have a cognitive exam during the year before death (n=234) or dropout (n=154) or during the month before censoring for dementia (n=70). Factors in imputed model included treatment group, demographic and health history variables, study site, and other cognitive scores. Higher Z-scores worse

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).

Outcome measures

Outcome measures
Measure	Ginkgo Biloba n=1545 Participants 120 mg twice daily, total 240 mg	Placebo n=1524 Participants Placebo 1 pill twice a day
Progression of Cognitive Decline in Standardized Z-score Scale. Higher Z-scores Indicate Worse Performance. Global Cognition (mean Z-score of 5 domains)	0.069 Z-score units Interval 0.064 to 0.074	0.071 Z-score units Interval 0.065 to 0.076
Progression of Cognitive Decline in Standardized Z-score Scale. Higher Z-scores Indicate Worse Performance. Memory (mean Z-score of 2 memory tests)	0.043 Z-score units Interval 0.034 to 0.051	0.041 Z-score units Interval 0.032 to 0.05
Progression of Cognitive Decline in Standardized Z-score Scale. Higher Z-scores Indicate Worse Performance. Attention (mean Z-score of 2 attention tests)	0.043 Z-score units Interval 0.037 to 0.05	0.048 Z-score units Interval 0.041 to 0.054
Progression of Cognitive Decline in Standardized Z-score Scale. Higher Z-scores Indicate Worse Performance. Visuospatial Abilities (mean Z-score of 2 tests)	0.107 Z-score units Interval 0.097 to 0.117	0.118 Z-score units Interval 0.108 to 0.128
Progression of Cognitive Decline in Standardized Z-score Scale. Higher Z-scores Indicate Worse Performance. Language (mean Z-score of 2 language tests)	0.045 Z-score units Interval 0.037 to 0.054	0.041 Z-score units Interval 0.033 to 0.048
Progression of Cognitive Decline in Standardized Z-score Scale. Higher Z-scores Indicate Worse Performance. Executive Functions (mean Z-score of 2 tests)	0.092 Z-score units Interval 0.086 to 0.099	0.089 Z-score units Interval 0.082 to 0.096

Adverse Events

Ginkgo Biloba

Serious events: 1000 serious events

Other events: 1504 other events

Deaths: 0 deaths

Placebo

Serious events: 961 serious events

Other events: 1469 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ginkgo Biloba n=1545 participants at risk EGb 761 Ginkgo biloba 120 mg twice daily	Placebo n=1524 participants at risk Placebo twice daily
General disorders Death	12.8% 197/1545 • Number of events 197 • Adverse event data were collected every six months at testing visits, and at interim 3 month adherence phone calls.	12.3% 188/1524 • Number of events 188 • Adverse event data were collected every six months at testing visits, and at interim 3 month adherence phone calls.
General disorders Bleeding	8.9% 138/1545 • Number of events 171 • Adverse event data were collected every six months at testing visits, and at interim 3 month adherence phone calls.	9.2% 140/1524 • Number of events 178 • Adverse event data were collected every six months at testing visits, and at interim 3 month adherence phone calls.
Vascular disorders Coronary Heart Disease Total	13.7% 211/1545 • Number of events 285 • Adverse event data were collected every six months at testing visits, and at interim 3 month adherence phone calls.	13.4% 204/1524 • Number of events 259 • Adverse event data were collected every six months at testing visits, and at interim 3 month adherence phone calls.
Vascular disorders Stroke	5.2% 80/1545 • Number of events 88 • Adverse event data were collected every six months at testing visits, and at interim 3 month adherence phone calls.	4.7% 71/1524 • Number of events 82 • Adverse event data were collected every six months at testing visits, and at interim 3 month adherence phone calls.
General disorders All other SAEs	24.2% 374/1545 • Number of events 1627 • Adverse event data were collected every six months at testing visits, and at interim 3 month adherence phone calls.	23.5% 358/1524 • Number of events 1647 • Adverse event data were collected every six months at testing visits, and at interim 3 month adherence phone calls.

Other adverse events

Other adverse events
Measure	Ginkgo Biloba n=1545 participants at risk EGb 761 Ginkgo biloba 120 mg twice daily	Placebo n=1524 participants at risk Placebo twice daily
General disorders non-hospitalized self-reported symptom	0.00% 0/1545 • Adverse event data were collected every six months at testing visits, and at interim 3 month adherence phone calls.	0.00% 0/1524 • Adverse event data were collected every six months at testing visits, and at interim 3 month adherence phone calls.
General disorders All adverse events	97.3% 1504/1545 • Number of events 1504 • Adverse event data were collected every six months at testing visits, and at interim 3 month adherence phone calls.	96.4% 1469/1524 • Number of events 1469 • Adverse event data were collected every six months at testing visits, and at interim 3 month adherence phone calls.
General disorders Self-reported non-hospitalized symptom collected every 6 months	97.3% 1504/1545 • Number of events 1504 • Adverse event data were collected every six months at testing visits, and at interim 3 month adherence phone calls.	96.4% 1469/1524 • Number of events 1469 • Adverse event data were collected every six months at testing visits, and at interim 3 month adherence phone calls.

Additional Information

Steven T. DeKosky MD

University of Virginia

Phone: 434-924-5118

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place