Ginkgo Biloba Prevention Trial in Older Individuals

This study has been completed.

Sponsor:

Collaborators:

Office of Dietary Supplements (ODS)

National Institute of Neurological Disorders and Stroke (NINDS)

National Institute on Aging (NIA)

National Heart, Lung, and Blood Institute (NHLBI)

Information provided by (Responsible Party):

National Center for Complementary and Alternative Medicine (NCCAM)

ClinicalTrials.gov Identifier:

NCT00010803

First received: February 2, 2001

Last updated: March 11, 2013

Last verified: March 2013

History of Changes

Results First Received: March 27, 2009

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Investigator); Primary Purpose: Prevention
Conditions:	Dementia Alzheimer's Disease
Interventions:	Drug: Ginkgo biloba Drug: Placebo

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups

	Description
Ginkgo Biloba	EGb 761 Ginkgo biloba 120 mg twice daily
Placebo	Placebo twice daily

Participant Flow: Overall Study

	Ginkgo Biloba	Placebo
STARTED	1545 ^[1]	1524 ^[1]
COMPLETED	1448 ^[2]	1426 ^[2]
NOT COMPLETED	97	98
Withdrawal by Subject	97	98

[1]	Randomized
[2]	Reached endpoint of dementia, death or completion

Baseline Characteristics

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Reporting Groups

	Description
Ginkgo Biloba	120 mg twice daily, total 240 mg
Placebo	Placebo 1 pill twice daily
Total	Total of all reporting groups

Baseline Measures

	Ginkgo Biloba	Placebo	Total
Number of Participants [units: participants]	1545	1524	3069
Age [units: participants]
<=18 years	0	0	0
Between 18 and 65 years	0	0	0
>=65 years	1545	1524	3069
Age [units: years] Mean ± Standard Deviation	79.1 ± 3.3	79.1 ± 3.3	79.1 ± 3.3
Gender [units: participants]
Female	702	716	1418
Male	843	808	1651
Region of Enrollment [units: participants]
United States	1545	1524	3069

Outcome Measures

Show All Outcome Measures

1. Primary:

Number of Participants With Incident Dementia [ Time Frame: Brief neuropsychological testing every 6 months, detailed testing annually, average 6.1 years follow up ]

Show Outcome Measure 1

2. Secondary:

Number of Participants With the Indicated Cardiovascular Disease or Mortality [ Time Frame: 6 months ]

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Measure Type	Secondary
Measure Title	Number of Participants With the Indicated Cardiovascular Disease or Mortality
Measure Description	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
Time Frame	6 months
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Total cohort of 3069 based on same design as primary outcome, ITT.

Reporting Groups

	Description
Ginkgo Biloba	120 mg twice daily, total 240 mg
Placebo	Placebo 1 pill twice a day

Measured Values

	Ginkgo Biloba	Placebo
Number of Participants Analyzed [units: participants]	1545	1524
Number of Participants With the Indicated Cardiovascular Disease or Mortality [units: Participants]
Total Mortality	197	188
Atherosclerotic CHD Mortality	45	42
Incident MI	68	60
Incident Angina	66	76
Incident CHD (MI &/or angina)	107	110
Incident CHF	112	122
Incident Stroke	73	59
Incident TIA	27	31
Incident CVD (stroke &/or TIA)	99	88
Total CHD and CVD	157	154

Statistical Analysis 1 for Number of Participants With the Indicated Cardiovascular Disease or Mortality

Groups ^[1]	All groups
Non-Inferiority/Equivalence Test ^[2]	Yes
Method ^[3]	Log Rank
P Value ^[4]	0.70
Hazard Ratio (HR) ^[5]	1.04
95% Confidence Interval	( 0.85 to 1.27 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Total Mortality
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	Previously provided
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
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Statistical Analysis 2 for Number of Participants With the Indicated Cardiovascular Disease or Mortality

Groups ^[1]	All groups
Non-Inferiority/Equivalence Test ^[2]	Yes
Method ^[3]	Log Rank
P Value ^[4]	0.78
Hazard Ratio (HR) ^[5]	1.06
95% Confidence Interval	( 0.70 to 1.62 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Atherosclerotic CHD mortality
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	Previously provided
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Number of Participants With the Indicated Cardiovascular Disease or Mortality

Groups ^[1]	All groups
Non-Inferiority/Equivalence Test ^[2]	Yes
Method ^[3]	Log Rank
P Value ^[4]	0.54
Hazard Ratio (HR) ^[5]	1.12
95% Confidence Interval	( 0.79 to 1.58 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Incident Myocardial Infarction
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	Previously provided
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for Number of Participants With the Indicated Cardiovascular Disease or Mortality

Groups ^[1]	All groups
Non-Inferiority/Equivalence Test ^[2]	Yes
Method ^[3]	Log Rank
P Value ^[4]	0.32
Hazard Ratio (HR) ^[5]	0.84
95% Confidence Interval	( 0.61 to 1.18 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Incident Angina
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	Previously Provided
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 5 for Number of Participants With the Indicated Cardiovascular Disease or Mortality

Groups ^[1]	All groups
Non-Inferiority/Equivalence Test ^[2]	Yes
Method ^[3]	Log Rank
P Value ^[4]	0.66
Hazard Ratio (HR) ^[5]	0.94
95% Confidence Interval	( 0.72 to 1.23 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Incident CHD
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	Previously provided
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 6 for Number of Participants With the Indicated Cardiovascular Disease or Mortality

Groups ^[1]	All groups
Non-Inferiority/Equivalence Test ^[2]	Yes
Method ^[3]	Log Rank
P Value ^[4]	0.48
Hazard Ratio (HR) ^[5]	0.91
95% Confidence Interval	( 0.71 to 1.18 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Incident CHF
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	Previously Provided
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 7 for Number of Participants With the Indicated Cardiovascular Disease or Mortality

Groups ^[1]	All groups
Non-Inferiority/Equivalence Test ^[2]	Yes
Method ^[3]	Log Rank
P Value ^[4]	0.25
Hazard Ratio (HR) ^[5]	0.87
95% Confidence Interval	( 0.52 to 1.45 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Incident Stroke
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	Previously provided
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 8 for Number of Participants With the Indicated Cardiovascular Disease or Mortality

Groups ^[1]	All groups
Non-Inferiority/Equivalence Test ^[2]	Yes
Method ^[3]	Log Rank
P Value ^[4]	0.59
Hazard Ratio (HR) ^[5]	0.87
95% Confidence Interval	( 0.52 to 1.45 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Incident TIA
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	Previously provided
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 9 for Number of Participants With the Indicated Cardiovascular Disease or Mortality

Groups ^[1]	All groups
Non-Inferiority/Equivalence Test ^[2]	Yes
Method ^[3]	Log Rank
P Value ^[4]	0.42
Cox Proportional Hazard ^[5]	1.12
95% Confidence Interval	( 0.84 to 1.50 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Incident CVD
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	Previously provided
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 10 for Number of Participants With the Indicated Cardiovascular Disease or Mortality

Groups ^[1]	All groups
Non-Inferiority/Equivalence Test ^[2]	Yes
Method ^[3]	Log Rank
P Value ^[4]	0.98
Hazard Ratio (HR) ^[5]	1.00
95% Confidence Interval	( 0.80 to 1.25 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Total CHD and CVD combined
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	Previously provided
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

3. Secondary:

Progression of Cognitive Decline in Standardized Z-score Scale. Higher Z-scores Indicate Worse Performance. [ Time Frame: 6 months/annually ]

Show Outcome Measure 3

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Steven T. DeKosky MD
Organization: University of Virginia
phone: 434-924-5118
e-mail: SD3ZC@hscmail.mcc.virginia.edu

Publications of Results:

DeKosky ST, Williamson JD, Fitzpatrick AL, Kronmal RA, Ives DG, Saxton JA, Lopez OL, Burke G, Carlson MC, Fried LP, Kuller LH, Robbins JA, Tracy RP, Woolard NF, Dunn L, Snitz BE, Nahin RL, Furberg CD; Ginkgo Evaluation of Memory (GEM) Study Investigators. Ginkgo biloba for prevention of dementia: a randomized controlled trial. JAMA. 2008 Nov 19;300(19):2253-62.

Other Publications:

Fitzpatrick AL, Fried LP, Williamson J, Crowley P, Posey D, Kwong L, Bonk J, Moyer R, Chabot J, Kidoguchi L, Furberg CD, DeKosky ST; GEM Study Investigators. Recruitment of the elderly into a pharmacologic prevention trial: the Ginkgo Evaluation of Memory Study experience. Contemp Clin Trials. 2006 Dec;27(6):541-53. Epub 2006 Jul 4.

DeKosky ST, Fitzpatrick A, Ives DG, Saxton J, Williamson J, Lopez OL, Burke G, Fried L, Kuller LH, Robbins J, Tracy R, Woolard N, Dunn L, Kronmal R, Nahin R, Furberg C; GEMS Investigators. The Ginkgo Evaluation of Memory (GEM) study: design and baseline data of a randomized trial of Ginkgo biloba extract in prevention of dementia. Contemp Clin Trials. 2006 Jun;27(3):238-53. Epub 2006 Apr 19.

Fitzpatrick AL, Buchanan CK, Nahin RL, Dekosky ST, Atkinson HH, Carlson MC, Williamson JD; Ginkgo Evaluation of Memory (GEM) Study Investigators. Associations of gait speed and other measures of physical function with cognition in a healthy cohort of elderly persons. J Gerontol A Biol Sci Med Sci. 2007 Nov;62(11):1244-51.

Nahin RL, Fitzpatrick AL, Williamson JD, Burke GL, Dekosky ST, Furberg C; GEM Study Investigators. Use of herbal medicine and other dietary supplements in community-dwelling older people: Baseline data from the ginkgo evaluation of memory study. J Am Geriatr Soc. 2006 Nov;54(11):1725-35.

Rosano C, Aizenstein HJ, Cochran JL, Saxton JA, De Kosky ST, Newman AB, Kuller LH, Lopez OL, Carter CS. Event-related functional magnetic resonance imaging investigation of executive control in very old individuals with mild cognitive impairment. Biol Psychiatry. 2005 Apr 1;57(7):761-7.

Rosano C, Aizenstein H, Cochran J, Saxton J, De Kosky S, Newman AB, Kuller LH, Lopez OL, Carter CS. Functional neuroimaging indicators of successful executive control in the oldest old. Neuroimage. 2005 Dec;28(4):881-9. Epub 2005 Oct 12.

Williamson JD, Vellas B, Furberg C, Nahin R, Dekosky ST. Comparison of the design differences between the Ginkgo Evaluation of Memory study and the GuidAge study. J Nutr Health Aging. 2008 Jan;12(1):73S-9S.

Snitz BE, Saxton J, Lopez OL, Ives DG, Dunn LO, Rapp SR, Carlson MC, Fitzpatrick AL, Dekosky ST; GEM study Investigators. Identifying mild cognitive impairment at baseline in the Ginkgo Evaluation of Memory (GEM) study. Aging Ment Health. 2009 Mar;13(2):171-82.

Publications automatically indexed to this study:

Kuller LH, Ives DG, Fitzpatrick AL, Carlson MC, Mercado C, Lopez OL, Burke GL, Furberg CD, DeKosky ST; Ginkgo Evaluation of Memory Study Investigators. Does Ginkgo biloba reduce the risk of cardiovascular events? Circ Cardiovasc Qual Outcomes. 2010 Jan 1;3(1):41-7. Epub 2009 Nov 24.

Snitz BE, O'Meara ES, Carlson MC, Arnold AM, Ives DG, Rapp SR, Saxton J, Lopez OL, Dunn LO, Sink KM, DeKosky ST; Ginkgo Evaluation of Memory (GEM) Study Investigators. Ginkgo biloba for preventing cognitive decline in older adults: a randomized trial. JAMA. 2009 Dec 23;302(24):2663-70.

Responsible Party:	National Center for Complementary and Alternative Medicine (NCCAM)
ClinicalTrials.gov Identifier:	NCT00010803 History of Changes
Obsolete Identifiers:	NCT00004535
Other Study ID Numbers:	U01 AT000162-01M
Study First Received:	February 2, 2001
Results First Received:	March 27, 2009
Last Updated:	March 11, 2013
Health Authority:	United States: Food and Drug Administration

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