Trial Outcomes & Findings for Effect of EGb761® on Brain Glucose Metabolism in Three Groups of Elderly Defined by Cognitive Functions (NCT NCT00814346)

NCT ID: NCT00814346

Last Updated: 2019-02-08

Results Overview

Following statistical parametric mapping (SPM) analyses were performed by the Commissariat à l'Energie Atomique (CEA): * The comparison between treatment groups separately for each group of elderly subjects (CNE and MC groups only) * The comparison between the two groups of elderly subjects (CNE and MC groups only) by treatment group FDG PET demonstrates reductions in the cerebral glucose metabolism that may occur a few years before the overt clinical manifestation of disease. SUVBSA2 = \[Brain radioactivity (Bq/cc)\] / \[Injected dose (MBq)/BSA2\] x \[Blood glucose (g/l)\] BSA2(m\^2) = 0.007184 x Height (cm)\^0.35 x weight (kg)\^0.80 Standardized Uptake Value (SUV) Body Surface Area (BSA)

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

49 participants

Primary outcome timeframe

From Baseline (Month 0) to Week 4 (Month 1) - Double blind phase

Results posted on

2019-02-08

Participant Flow

A total of 63 participants were screened of which 49 subjects were randomised to either EGb761 and Placebo treatment groups (double-blind period). The 49 randomised subjects consisted of three groups of elderly subjects: Cognitively normal elderly (CNE), Memory Complaint (MC) and Alzheimer's Disease (AD).

Participant milestones

Participant milestones
Measure
EGb761 120 mg
EGb761 120 mg tablet twice a day for 4 weeks (Double-blind phase) for CNE, MC, and AD patients and 17 months (Open phase) for CNE and MC patients
Placebo
Placebo 1 tablet twice a day for 4 weeks CNE, MC, and AD patients
Double-blind Phase (4 Weeks)
STARTED
23
26
Double-blind Phase (4 Weeks)
CNE
10
13
Double-blind Phase (4 Weeks)
MC
10
11
Double-blind Phase (4 Weeks)
AD
3
2
Double-blind Phase (4 Weeks)
COMPLETED
23
23
Double-blind Phase (4 Weeks)
NOT COMPLETED
0
3
Open Phase (17 Months)
STARTED
41
0
Open Phase (17 Months)
CNE
21
0
Open Phase (17 Months)
MC
20
0
Open Phase (17 Months)
AD
0
0
Open Phase (17 Months)
COMPLETED
31
0
Open Phase (17 Months)
NOT COMPLETED
10
0

Reasons for withdrawal

Reasons for withdrawal
Measure
EGb761 120 mg
EGb761 120 mg tablet twice a day for 4 weeks (Double-blind phase) for CNE, MC, and AD patients and 17 months (Open phase) for CNE and MC patients
Placebo
Placebo 1 tablet twice a day for 4 weeks CNE, MC, and AD patients
Double-blind Phase (4 Weeks)
Adverse Event
0
1
Double-blind Phase (4 Weeks)
Not otherwise specified
0
2
Open Phase (17 Months)
Adverse Event
5
0
Open Phase (17 Months)
Consent
2
0
Open Phase (17 Months)
Lost to Follow-up
2
0
Open Phase (17 Months)
Not otherwise specified
1
0

Baseline Characteristics

Effect of EGb761® on Brain Glucose Metabolism in Three Groups of Elderly Defined by Cognitive Functions

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
EGb761 120 mg
n=23 Participants
EGb761 120 mg tablet twice a day for 4 weeks (Double-blind phase) for CNE, MC, and AD patients and 17 months (Open phase) for CNE and MC patients
Placebo
n=26 Participants
Placebo 1 tablet twice a day for 4 weeks CNE, MC, and AD patients
Total
n=49 Participants
Total of all reporting groups
Age, Continuous
75.1 years
STANDARD_DEVIATION 6.2 • n=5 Participants
76.6 years
STANDARD_DEVIATION 5.3 • n=7 Participants
75.85 years
STANDARD_DEVIATION 5.25 • n=5 Participants
Sex: Female, Male
Female
15 Participants
n=5 Participants
17 Participants
n=7 Participants
32 Participants
n=5 Participants
Sex: Female, Male
Male
8 Participants
n=5 Participants
9 Participants
n=7 Participants
17 Participants
n=5 Participants
Body Mass Index (BMI)
24.49 kg/m^2
STANDARD_DEVIATION 4.46 • n=5 Participants
25.03 kg/m^2
STANDARD_DEVIATION 4.40 • n=7 Participants
24.76 kg/m^2
STANDARD_DEVIATION 4.43 • n=5 Participants
Educational Level
Level 1: Primary only
1 participants
n=5 Participants
0 participants
n=7 Participants
1 participants
n=5 Participants
Educational Level
Level 2: School certificate
2 participants
n=5 Participants
5 participants
n=7 Participants
7 participants
n=5 Participants
Educational Level
Level 3: Completed secondary
3 participants
n=5 Participants
6 participants
n=7 Participants
9 participants
n=5 Participants
Educational Level
Level 4: University
17 participants
n=5 Participants
15 participants
n=7 Participants
32 participants
n=5 Participants

PRIMARY outcome

Timeframe: From Baseline (Month 0) to Week 4 (Month 1) - Double blind phase

Population: Intention to treat (ITT) population: All treated CNE and MC patients

Following statistical parametric mapping (SPM) analyses were performed by the Commissariat à l'Energie Atomique (CEA): * The comparison between treatment groups separately for each group of elderly subjects (CNE and MC groups only) * The comparison between the two groups of elderly subjects (CNE and MC groups only) by treatment group FDG PET demonstrates reductions in the cerebral glucose metabolism that may occur a few years before the overt clinical manifestation of disease. SUVBSA2 = \[Brain radioactivity (Bq/cc)\] / \[Injected dose (MBq)/BSA2\] x \[Blood glucose (g/l)\] BSA2(m\^2) = 0.007184 x Height (cm)\^0.35 x weight (kg)\^0.80 Standardized Uptake Value (SUV) Body Surface Area (BSA)

Outcome measures

Outcome measures
Measure
EGb 120 mg (Open Phase - CNE)
n=10 Participants
EGb761 120 mg tablet twice a day for 17 months (open phase) for CNE patients
EGb 120 mg (Open Phase - MC)
n=11 Participants
EGb761 120 mg 17 months (open phase) for MC patients
EGb761 120 mg (MC)
n=10 Participants
EGb761 120 mg tablet twice a day for 4 weeks (Double-blind phase) for CNE, MC, and AD patients
Placebo (MC)
n=10 Participants
Placebo 1 tablet twice a day for 4 weeks for CNE, MC and AD patients
Change in Brain Glucose Metabolism Measured Using 18-Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET)
Cerebellum
-3.40 SUVBSA2
Interval -16.4 to 18.7
-1.07 SUVBSA2
Interval -22.8 to 33.5
-7.58 SUVBSA2
Interval -29.7 to 26.4
-3.09 SUVBSA2
Interval -16.4 to 22.4
Change in Brain Glucose Metabolism Measured Using 18-Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET)
Left cerebral cortex
-8.56 SUVBSA2
Interval -14.0 to 22.0
2.25 SUVBSA2
Interval -28.9 to 35.9
0.44 SUVBSA2
Interval -36.3 to 35.8
-0.32 SUVBSA2
Interval -33.9 to 30.7
Change in Brain Glucose Metabolism Measured Using 18-Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET)
Left thalamus
-8.46 SUVBSA2
Interval -23.3 to 25.1
-0.06 SUVBSA2
Interval -39.6 to 37.4
-2.09 SUVBSA2
Interval -35.2 to 30.1
-6.19 SUVBSA2
Interval -38.9 to 31.2
Change in Brain Glucose Metabolism Measured Using 18-Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET)
Left caudate nucleus
-0.68 SUVBSA2
Interval -28.0 to 29.1
4.60 SUVBSA2
Interval -23.8 to 49.6
2.16 SUVBSA2
Interval -35.8 to 53.4
3.27 SUVBSA2
Interval -51.4 to 25.3
Change in Brain Glucose Metabolism Measured Using 18-Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET)
Left putamen nucleus
-1.91 SUVBSA2
Interval -23.7 to 26.3
-0.19 SUVBSA2
Interval -23.5 to 55.8
2.15 SUVBSA2
Interval -46.0 to 46.2
-6.20 SUVBSA2
Interval -49.1 to 39.8
Change in Brain Glucose Metabolism Measured Using 18-Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET)
Left ventral striatum
1.49 SUVBSA2
Interval -53.5 to 19.7
-7.29 SUVBSA2
Interval -30.4 to 67.5
2.37 SUVBSA2
Interval -22.3 to 24.4
-4.62 SUVBSA2
Interval -53.8 to 33.8
Change in Brain Glucose Metabolism Measured Using 18-Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET)
Left globus pallidus
-4.33 SUVBSA2
Interval -26.3 to 19.4
-1.26 SUVBSA2
Interval -9.4 to 39.2
-7.75 SUVBSA2
Interval -28.5 to 14.0
-8.72 SUVBSA2
Interval -24.7 to 26.3
Change in Brain Glucose Metabolism Measured Using 18-Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET)
Right cerebral cortex
-7.49 SUVBSA2
Interval -25.3 to 21.4
0.19 SUVBSA2
Interval -29.4 to 38.2
-7.11 SUVBSA2
Interval -32.5 to 35.5
-6.59 SUVBSA2
Interval -36.1 to 31.3
Change in Brain Glucose Metabolism Measured Using 18-Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET)
Right thalamus
-7.40 SUVBSA2
Interval -27.3 to 28.7
-2.05 SUVBSA2
Interval -46.6 to 41.5
-3.87 SUVBSA2
Interval -29.9 to 28.1
-7.72 SUVBSA2
Interval -43.4 to 31.1
Change in Brain Glucose Metabolism Measured Using 18-Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET)
Right caudate nucleus
-1.59 SUVBSA2
Interval -36.2 to 29.1
-0.66 SUVBSA2
Interval -23.7 to 46.0
-9.21 SUVBSA2
Interval -34.2 to 40.9
-6.45 SUVBSA2
Interval -41.3 to 16.7
Change in Brain Glucose Metabolism Measured Using 18-Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET)
Right putamen nucleus
-6.31 SUVBSA2
Interval -42.9 to 30.8
-2.73 SUVBSA2
Interval -39.1 to 52.8
-8.84 SUVBSA2
Interval -41.7 to 41.8
-5.36 SUVBSA2
Interval -50.4 to 25.5
Change in Brain Glucose Metabolism Measured Using 18-Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET)
Right ventral striatum
-7.08 SUVBSA2
Interval -23.8 to 32.8
-0.76 SUVBSA2
Interval -43.7 to 41.5
-8.21 SUVBSA2
Interval -27.6 to 65.5
-0.59 SUVBSA2
Interval -51.4 to 27.2
Change in Brain Glucose Metabolism Measured Using 18-Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET)
Right globus pallidus
-2.04 SUVBSA2
Interval -21.1 to 17.3
-1.72 SUVBSA2
Interval -22.1 to 40.4
-5.99 SUVBSA2
Interval -23.0 to 33.7
-1.24 SUVBSA2
Interval -35.0 to 17.2

SECONDARY outcome

Timeframe: From Baseline (Month 0) to Month 18

Population: ITT population. N=Number of subjects with assessment.

Brain glucose metabolism measured by 18FDG PET SUVBSA2 = \[Brain radioactivity (Bq/cc)\] / \[Injected dose (MBq)/BSA2\] x \[Blood glucose (g/l)\] BSA2(m\^2) = 0.007184 x Height (cm)\^0.35 x weight (kg)\^0.80

Outcome measures

Outcome measures
Measure
EGb 120 mg (Open Phase - CNE)
n=18 Participants
EGb761 120 mg tablet twice a day for 17 months (open phase) for CNE patients
EGb 120 mg (Open Phase - MC)
n=14 Participants
EGb761 120 mg 17 months (open phase) for MC patients
EGb761 120 mg (MC)
EGb761 120 mg tablet twice a day for 4 weeks (Double-blind phase) for CNE, MC, and AD patients
Placebo (MC)
Placebo 1 tablet twice a day for 4 weeks for CNE, MC and AD patients
Change in Brain Glucose Metabolism in the MC and CNE Groups
Cerebellum
-0.07 SUVBSA2
Interval -0.3 to 0.1
0 SUVBSA2
Interval -0.5 to 0.2
Change in Brain Glucose Metabolism in the MC and CNE Groups
Left cerebral cortex
-0.06 SUVBSA2
Interval -0.3 to 0.1
-0.08 SUVBSA2
Interval -0.5 to 0.1
Change in Brain Glucose Metabolism in the MC and CNE Groups
Left thalamus
-0.03 SUVBSA2
Interval -0.2 to 0.1
-0.02 SUVBSA2
Interval -0.8 to 0.1
Change in Brain Glucose Metabolism in the MC and CNE Groups
Left caudate nucleus
-0.11 SUVBSA2
Interval -0.8 to 0.2
-0.01 SUVBSA2
Interval -0.6 to 0.2
Change in Brain Glucose Metabolism in the MC and CNE Groups
Left putamen nucleus
0.07 SUVBSA2
Interval -0.3 to 0.2
0.00 SUVBSA2
Interval -0.5 to 0.3
Change in Brain Glucose Metabolism in the MC and CNE Groups
Left ventral striatum
-0.05 SUVBSA2
Interval -0.5 to 0.3
-0.09 SUVBSA2
Interval -0.5 to 0.1
Change in Brain Glucose Metabolism in the MC and CNE Groups
Left globus pallidus
0.00 SUVBSA2
Interval -0.3 to 0.2
-0.01 SUVBSA2
Interval -0.2 to 0.1
Change in Brain Glucose Metabolism in the MC and CNE Groups
Right cerebral cortex
-0.07 SUVBSA2
Interval -0.3 to 0.1
-0.06 SUVBSA2
Interval -0.3 to 0.1
Change in Brain Glucose Metabolism in the MC and CNE Groups
Right thalamus
0.04 SUVBSA2
Interval -0.3 to 0.2
-0.00 SUVBSA2
Interval -0.9 to 0.2
Change in Brain Glucose Metabolism in the MC and CNE Groups
Right caudate nucleus
0.03 SUVBSA2
Interval -0.6 to 0.2
-0.02 SUVBSA2
Interval -0.6 to 0.3
Change in Brain Glucose Metabolism in the MC and CNE Groups
Right putamen nucleus
0.04 SUVBSA2
Interval -0.5 to 0.2
0.02 SUVBSA2
Interval -0.3 to 0.3
Change in Brain Glucose Metabolism in the MC and CNE Groups
Right ventral striatum
0.01 SUVBSA2
Interval -0.4 to 0.3
-0.05 SUVBSA2
Interval -0.6 to 0.4
Change in Brain Glucose Metabolism in the MC and CNE Groups
Right globus pallidus
0.06 SUVBSA2
Interval -0.3 to 0.4
0.06 SUVBSA2
Interval -0.2 to 0.6

SECONDARY outcome

Timeframe: From Baseline (Month 0) to Month 9

Population: ITT population. N=Number of subjects with assessment.

CDR is a structured interview to collect information regarding subject's memory in a standard way from both the patient and the helper. Scores are calculated using below scale; q CDR=No dementia (score: 0), q CDR=Very mild dementia (score: 0.5), q CDR=Mild dementia (score: 1), q CDR=Moderate dementia (score: 2) and q CDR=Severe dementia (score: 3).

Outcome measures

Outcome measures
Measure
EGb 120 mg (Open Phase - CNE)
n=20 Participants
EGb761 120 mg tablet twice a day for 17 months (open phase) for CNE patients
EGb 120 mg (Open Phase - MC)
n=18 Participants
EGb761 120 mg 17 months (open phase) for MC patients
EGb761 120 mg (MC)
EGb761 120 mg tablet twice a day for 4 weeks (Double-blind phase) for CNE, MC, and AD patients
Placebo (MC)
Placebo 1 tablet twice a day for 4 weeks for CNE, MC and AD patients
Change in Cognitive Tests-Clinical Dementia Rating (CDR) Score in MC and CNE Groups
0.00 CDR overall score
Interval 0.0 to 0.5
0.00 CDR overall score
Interval -0.5 to 0.5

SECONDARY outcome

Timeframe: From Baseline (Month 0) to Month 9

Population: ITT population. N=Number of subjects with assessment.

The Geriatric Depression Scale is a self-administered depression scale, which was developed as a basic screening measure for depression in older adults. By "yes" or "no" answers, scores permit to classify patients into groups of "severely depressed" (score of 21 to 30), "moderately depressed" (score of 11 to 20) and "normal" (score of 0 to10). It takes10 to 15 minutes to administer.

Outcome measures

Outcome measures
Measure
EGb 120 mg (Open Phase - CNE)
n=19 Participants
EGb761 120 mg tablet twice a day for 17 months (open phase) for CNE patients
EGb 120 mg (Open Phase - MC)
n=17 Participants
EGb761 120 mg 17 months (open phase) for MC patients
EGb761 120 mg (MC)
EGb761 120 mg tablet twice a day for 4 weeks (Double-blind phase) for CNE, MC, and AD patients
Placebo (MC)
Placebo 1 tablet twice a day for 4 weeks for CNE, MC and AD patients
Change in Cognitive Tests-Geriatric Depression Scale (GDS) Score in MC and CNE Groups
-2.00 GDS Score
Interval -6.0 to 8.0
0.00 GDS Score
Interval -5.0 to 9.0

SECONDARY outcome

Timeframe: From Baseline (Month 0) to Month 9

Population: ITT population. N=Number of subjects with assessment.

Subjects completed a verbal fluency test. Higher scores represent higher levels of verbal fluency. Minimum score=0 and Maximum score= N/A. Letter fluency: this task consists of enouncing as many words as possible that begin with a given letter of the alphabet. Participants are not allowed to use proper names. Categorical fluency: in this task participants are asked to list as many words as possible that belong to a given semantic category (e.g. animals, fruits, towns) Each condition foresees 60 sec of word generation time. The score corresponds to the number of words correctly given. The verbal fluency task measures semantic storage and executive retrieval functions.

Outcome measures

Outcome measures
Measure
EGb 120 mg (Open Phase - CNE)
n=18 Participants
EGb761 120 mg tablet twice a day for 17 months (open phase) for CNE patients
EGb 120 mg (Open Phase - MC)
n=18 Participants
EGb761 120 mg 17 months (open phase) for MC patients
EGb761 120 mg (MC)
EGb761 120 mg tablet twice a day for 4 weeks (Double-blind phase) for CNE, MC, and AD patients
Placebo (MC)
Placebo 1 tablet twice a day for 4 weeks for CNE, MC and AD patients
Change in Cognitive Tests-Verbal Fluency in MC and CNE Groups
Categorical verbal fluency
-1.50 Number of good answers
Interval -14.0 to 11.0
-2.00 Number of good answers
Interval -16.0 to 6.0
Change in Cognitive Tests-Verbal Fluency in MC and CNE Groups
Lexical verbal fluency
-1.00 Number of good answers
Interval -14.0 to 10.0
2.00 Number of good answers
Interval -18.0 to 22.0

SECONDARY outcome

Timeframe: From Baseline (Month 0) to Month 9

Population: ITT population. N=Number of subjects with assessment.

MMSE is a brief screening instrument used to assess cognitive function in elderly participants. It assesses orientation, memory, attention, ability to name objects, follow verbal and written commands, write a sentence, and copy figures. Total score ranges from 0 to 30, with a lower score indicating greater disease severity.

Outcome measures

Outcome measures
Measure
EGb 120 mg (Open Phase - CNE)
n=19 Participants
EGb761 120 mg tablet twice a day for 17 months (open phase) for CNE patients
EGb 120 mg (Open Phase - MC)
n=18 Participants
EGb761 120 mg 17 months (open phase) for MC patients
EGb761 120 mg (MC)
EGb761 120 mg tablet twice a day for 4 weeks (Double-blind phase) for CNE, MC, and AD patients
Placebo (MC)
Placebo 1 tablet twice a day for 4 weeks for CNE, MC and AD patients
Change in Cognitive Tests-Mini Mental Status Examination (MMSE) Score in MC and CNE Groups
0.00 MMSE Score
Interval -2.0 to 1.0
0.00 MMSE Score
Interval -6.0 to 4.0

SECONDARY outcome

Timeframe: From Baseline (Month 0) to Month 9

Population: ITT population. N=Number of subjects with assessment.

Clock drawing test is a visuo-constructive task, where subjects are asked to draw the face of a clock in a pre-drawn circle and then to draw in the arms to denote 16:45 (a quarter to five). The drawing can then be evaluated by a quantitative scoring method, which is based on the degree of completion of the drawing. The scoring system ranges from 0 to 6 with higher scores reflecting a greater number of errors and more impairment.

Outcome measures

Outcome measures
Measure
EGb 120 mg (Open Phase - CNE)
n=18 Participants
EGb761 120 mg tablet twice a day for 17 months (open phase) for CNE patients
EGb 120 mg (Open Phase - MC)
n=18 Participants
EGb761 120 mg 17 months (open phase) for MC patients
EGb761 120 mg (MC)
EGb761 120 mg tablet twice a day for 4 weeks (Double-blind phase) for CNE, MC, and AD patients
Placebo (MC)
Placebo 1 tablet twice a day for 4 weeks for CNE, MC and AD patients
Change in Cognitive Tests-Clock Drawing Test Score in MC and CNE Groups
0.00 Clock drawing test score
Interval -3.0 to 2.0
0.00 Clock drawing test score
Interval -5.0 to 3.0

SECONDARY outcome

Timeframe: From Baseline (Month 0) to Month 9

Population: ITT population. N=Number of subjects with assessment.

Cube drawing: Subjects are asked to draw a cube by heart. In case of failure, a model of a cube is given to the subjects to copy. The score system ranges from 0 (worse score) to 6 (best score). Score calculation is following: 1 point by face with 4 sides, 2 points for each face where each angle should be respected.

Outcome measures

Outcome measures
Measure
EGb 120 mg (Open Phase - CNE)
n=18 Participants
EGb761 120 mg tablet twice a day for 17 months (open phase) for CNE patients
EGb 120 mg (Open Phase - MC)
n=18 Participants
EGb761 120 mg 17 months (open phase) for MC patients
EGb761 120 mg (MC)
EGb761 120 mg tablet twice a day for 4 weeks (Double-blind phase) for CNE, MC, and AD patients
Placebo (MC)
Placebo 1 tablet twice a day for 4 weeks for CNE, MC and AD patients
Change in Cognitive Tests-Cube Drawing Test Score in MC and CNE Groups
0.00 Cube drawing test score
Interval -2.0 to 1.0
0.00 Cube drawing test score
Interval -4.0 to 5.0

SECONDARY outcome

Timeframe: From Baseline (Month 0) to Month 9

Population: ITT population. N=Number of subjects with assessment.

Free and Cued Selective Reminding Test (FCSRT) Assessment of verbal episodic memory. By this test performances in free recalls, cued recalls and in a recognition task can be analysed, because the process of encoding is controlled. Subjects are asked to remember a list of 16 words. Three tasks of free and cued recalls, as well as one recognition task and one delayed recall give the scores. Total recall is obtained by the addition of cued recalls to free recalls. Maximum score is 48 for immediate: 16 words X 3 corresponding to immediate free recall + immediate cued recall + immediate recognition test. Maximum score is 64 (better score) when delayed recall : 16 words X 4 . The minimum score is 0 (worse).

Outcome measures

Outcome measures
Measure
EGb 120 mg (Open Phase - CNE)
n=18 Participants
EGb761 120 mg tablet twice a day for 17 months (open phase) for CNE patients
EGb 120 mg (Open Phase - MC)
n=18 Participants
EGb761 120 mg 17 months (open phase) for MC patients
EGb761 120 mg (MC)
EGb761 120 mg tablet twice a day for 4 weeks (Double-blind phase) for CNE, MC, and AD patients
Placebo (MC)
Placebo 1 tablet twice a day for 4 weeks for CNE, MC and AD patients
Change in Cognitive Tests in MC and CNE Groups - Total Immediate Recall and Delayed Recall Scores of the Free and Cued Selective Reminding Test (FCSRT)
Total Immediate Recall Score
1.00 Recall score
Interval -1.0 to 10.0
0.00 Recall score
Interval -10.0 to 11.0
Change in Cognitive Tests in MC and CNE Groups - Total Immediate Recall and Delayed Recall Scores of the Free and Cued Selective Reminding Test (FCSRT)
Total Delayed Recall Score
0.00 Recall score
Interval -4.0 to 6.0
0.00 Recall score
Interval -4.0 to 5.0

SECONDARY outcome

Timeframe: From Baseline (Month 0) to Month 9

Population: ITT population. N=Number of subjects with assessment.

Subjects are asked to memorize two short stories, one consisting of 24, the other one of 26 information units. After the stories have been read aloud by the investigator, subjects are asked to enounce all items of information they can remember (free recall). Correctly reported items are added for each story. This test applies analytical capacities, as well as auditive and verbal synthesis, working memory and episodic memory. Score range from 0(worst) to 75 (better).

Outcome measures

Outcome measures
Measure
EGb 120 mg (Open Phase - CNE)
n=18 Participants
EGb761 120 mg tablet twice a day for 17 months (open phase) for CNE patients
EGb 120 mg (Open Phase - MC)
n=17 Participants
EGb761 120 mg 17 months (open phase) for MC patients
EGb761 120 mg (MC)
EGb761 120 mg tablet twice a day for 4 weeks (Double-blind phase) for CNE, MC, and AD patients
Placebo (MC)
Placebo 1 tablet twice a day for 4 weeks for CNE, MC and AD patients
Change in Cognitive Tests-Age-Adjusted Logical Memory (MEM III) in MC and CNE Groups
1.00 Age adjusted score
Interval -5.0 to 6.0
-1.00 Age adjusted score
Interval -4.0 to 7.0

SECONDARY outcome

Timeframe: From Baseline (Month 0) to Month 9

Population: ITT population. N=Number of subjects with assessment.

Wechsler Adult Intelligence Scale (WAIS) In this test subjects are asked to say how two seemingly dissimilar items might in fact be similar (14 item couples). This test involves especially abstract thinking and concept capacities. Cognitive Tests-Age-Adjusted Wechsler Adult Intelligence Scale (WAIS): 19 tests on similarities. The items 1 to 5 are graded from 1 (good) to 0 (bad), and the items 6 to 19 are graded from 2 (good) to 0 (bad). Item 6 and 7 can be repeated. At the end, the worst total score is 0, the best total score is 33.

Outcome measures

Outcome measures
Measure
EGb 120 mg (Open Phase - CNE)
n=17 Participants
EGb761 120 mg tablet twice a day for 17 months (open phase) for CNE patients
EGb 120 mg (Open Phase - MC)
n=18 Participants
EGb761 120 mg 17 months (open phase) for MC patients
EGb761 120 mg (MC)
EGb761 120 mg tablet twice a day for 4 weeks (Double-blind phase) for CNE, MC, and AD patients
Placebo (MC)
Placebo 1 tablet twice a day for 4 weeks for CNE, MC and AD patients
Change in Cognitive Tests-Age-Adjusted Wechsler Adult Intelligence Scale (WAIS) in MC and CNE Groups
1.00 Age adjusted score
Interval -3.0 to 5.0
1.00 Age adjusted score
Interval -3.0 to 5.0

SECONDARY outcome

Timeframe: From Baseline (Month 0) to Month 9

Population: ITT population. N=Number of subjects with assessment.

TMT is a neuropsychological test of visual attention and task switching. The task requires a subject to 'connect-the-dots' of 25 consecutive numbers (1,2,3,etc.) on a sheet of paper or computer screen. The goal of the subject is to finish the test as quickly as possible and the time taken to complete the test is used as the primary performance metric (in seconds). The maximum time allowed is 300 seconds. A negative change score indicates improvement. First, in the TMT A, the subject has to connect numbers increasingly as fast as possible. The TMT B requires the subject to connect and letters in an alternating pattern (1-A-2-B-3-C, etc.) in as little time as possible.

Outcome measures

Outcome measures
Measure
EGb 120 mg (Open Phase - CNE)
n=21 Participants
EGb761 120 mg tablet twice a day for 17 months (open phase) for CNE patients
EGb 120 mg (Open Phase - MC)
n=20 Participants
EGb761 120 mg 17 months (open phase) for MC patients
EGb761 120 mg (MC)
EGb761 120 mg tablet twice a day for 4 weeks (Double-blind phase) for CNE, MC, and AD patients
Placebo (MC)
Placebo 1 tablet twice a day for 4 weeks for CNE, MC and AD patients
Change in Cognitive Tests-Time to Perform Trail Making Test (TMT) in MC and CNE Groups
Task A (N=17,18)
2.00 Seconds
Interval -43.0 to 41.0
2.50 Seconds
Interval -18.0 to 31.0
Change in Cognitive Tests-Time to Perform Trail Making Test (TMT) in MC and CNE Groups
Task B (N=17,16)
0.00 Seconds
Interval -200.0 to 56.0
-5.50 Seconds
Interval -57.0 to 113.0

SECONDARY outcome

Timeframe: At Month 9

Population: ITT population. N=Number of subjects with assessment

The Diagnostic and Statistical Manual of Mental Disorders: 4th Edition of the American Psychiatric Association (DSM-IV, 1994) also outlines diagnostic criteria for dementia of the Alzheimer's type that are generally consistent with the NINCDS-ADRDA criteria. National Institute of Neurological and Communicative Diseases and Stroke / Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA)

Outcome measures

Outcome measures
Measure
EGb 120 mg (Open Phase - CNE)
n=21 Participants
EGb761 120 mg tablet twice a day for 17 months (open phase) for CNE patients
EGb 120 mg (Open Phase - MC)
n=20 Participants
EGb761 120 mg 17 months (open phase) for MC patients
EGb761 120 mg (MC)
EGb761 120 mg tablet twice a day for 4 weeks (Double-blind phase) for CNE, MC, and AD patients
Placebo (MC)
Placebo 1 tablet twice a day for 4 weeks for CNE, MC and AD patients
Number of Subjects Conversion to Alzheimer's Dementia Diagnosed According to the DSM IV (Diagnostic of Dementia)
0 participants
1 participants

SECONDARY outcome

Timeframe: At Month 9

Population: ITT population. N=Number of subjects with assessment.

The most widely accepted diagnostic criteria for probable AD are those offered by the National Institute of Neurological and Communicative Disorders and Stroke and by the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA; McKhann et al., 1984). These criteria include the presence of dementia established by clinical examination and confirmed by neuropsychological testing. The dementia is described as involving multiple, progressive cognitive deficits in older persons in the absence of disturbances of consciousness, presence of psychoactive substances, or any other medical, neurological, or psychiatric conditions that might in and of themselves account for these progressive deficits.

Outcome measures

Outcome measures
Measure
EGb 120 mg (Open Phase - CNE)
n=21 Participants
EGb761 120 mg tablet twice a day for 17 months (open phase) for CNE patients
EGb 120 mg (Open Phase - MC)
n=20 Participants
EGb761 120 mg 17 months (open phase) for MC patients
EGb761 120 mg (MC)
EGb761 120 mg tablet twice a day for 4 weeks (Double-blind phase) for CNE, MC, and AD patients
Placebo (MC)
Placebo 1 tablet twice a day for 4 weeks for CNE, MC and AD patients
Number of Subjects Conversion to Alzheimer's Dementia Diagnosed According to NINCDS-ADRDA (Diagnostic of Alzheimer's)
0 participants
1 participants

SECONDARY outcome

Timeframe: From Baseline (Month 0) to Month 18

Population: ITT population. N=Number of subjects with assessment.

CDR is a structured interview to collect information regarding subject's memory in a standard way from both the patient and the helper. Scores are calculated using below scale; q CDR=No dementia (score: 0), q CDR=Very mild dementia (score: 0.5), q CDR=Mild dementia (score: 1), q CDR=Moderate dementia (score: 2) and q CDR=Severe dementia (score: 3)

Outcome measures

Outcome measures
Measure
EGb 120 mg (Open Phase - CNE)
n=19 Participants
EGb761 120 mg tablet twice a day for 17 months (open phase) for CNE patients
EGb 120 mg (Open Phase - MC)
n=12 Participants
EGb761 120 mg 17 months (open phase) for MC patients
EGb761 120 mg (MC)
EGb761 120 mg tablet twice a day for 4 weeks (Double-blind phase) for CNE, MC, and AD patients
Placebo (MC)
Placebo 1 tablet twice a day for 4 weeks for CNE, MC and AD patients
Change in Cognitive Tests-CDR Score in MC and CNE Groups
0.00 CDR overall score
Interval 0.0 to 0.5
0.00 CDR overall score
Interval -0.5 to 0.0

SECONDARY outcome

Timeframe: From Baseline (Month 0) to Month 18

Population: ITT population. N=Number of subjects with assessment.

The Geriatric Depression Scale is a self-administered depression scale, which was developed as a basic screening measure for depression in older adults. By "yes" or "no" answers, scores permit to classify patients into groups of "severely depressed" (score of 21 to 30), "moderately depressed" (score of 11 to 20) and "normal" (score of 0 to10). It takes10 to 15 minutes to administer.

Outcome measures

Outcome measures
Measure
EGb 120 mg (Open Phase - CNE)
n=19 Participants
EGb761 120 mg tablet twice a day for 17 months (open phase) for CNE patients
EGb 120 mg (Open Phase - MC)
n=12 Participants
EGb761 120 mg 17 months (open phase) for MC patients
EGb761 120 mg (MC)
EGb761 120 mg tablet twice a day for 4 weeks (Double-blind phase) for CNE, MC, and AD patients
Placebo (MC)
Placebo 1 tablet twice a day for 4 weeks for CNE, MC and AD patients
Change in Cognitive Tests-GDS Score in MC and CNE Groups
1.00 GDS Score
Interval -7.0 to 17.0
0.50 GDS Score
Interval -5.0 to 7.0

SECONDARY outcome

Timeframe: From Baseline (Month 0) to Month 18

Population: ITT population. N=Number of subjects with assessment.

Subjects completed a verbal fluency test. Higher scores represent higher levels of verbal fluency. Minimum score=0 and Maximum score= N/A. Letter fluency: this task consists of enouncing as many words as possible that begin with a given letter of the alphabet. Participants are not allowed to use proper names. Categorical fluency: in this task participants are asked to list as many words as possible that belong to a given semantic category (e.g. animals, fruits, towns) Each condition foresees 60 sec of word generation time. The score corresponds to the number of words correctly given. The verbal fluency task measures semantic storage and executive retrieval functions.

Outcome measures

Outcome measures
Measure
EGb 120 mg (Open Phase - CNE)
n=19 Participants
EGb761 120 mg tablet twice a day for 17 months (open phase) for CNE patients
EGb 120 mg (Open Phase - MC)
n=12 Participants
EGb761 120 mg 17 months (open phase) for MC patients
EGb761 120 mg (MC)
EGb761 120 mg tablet twice a day for 4 weeks (Double-blind phase) for CNE, MC, and AD patients
Placebo (MC)
Placebo 1 tablet twice a day for 4 weeks for CNE, MC and AD patients
Change in Cognitive Tests-Verbal Fluency in MC and CNE Groups
categorical verbal fluency
-1.00 Number of good answers
Interval -18.0 to 20.0
1.00 Number of good answers
Interval -9.0 to 10.0
Change in Cognitive Tests-Verbal Fluency in MC and CNE Groups
lexical verbal fluency
-1.00 Number of good answers
Interval -16.0 to 18.0
1.50 Number of good answers
Interval -7.0 to 22.0

SECONDARY outcome

Timeframe: From Baseline (Month 0) to Month 18

Population: ITT population. N=Number of subjects with assessment.

MMSE is a brief screening instrument used to assess cognitive function in elderly participants. It assesses orientation, memory, attention, ability to name objects, follow verbal and written commands, write a sentence, and copy figures. Total score ranges from 0 to 30, with a lower score indicating greater disease severity.

Outcome measures

Outcome measures
Measure
EGb 120 mg (Open Phase - CNE)
n=19 Participants
EGb761 120 mg tablet twice a day for 17 months (open phase) for CNE patients
EGb 120 mg (Open Phase - MC)
n=12 Participants
EGb761 120 mg 17 months (open phase) for MC patients
EGb761 120 mg (MC)
EGb761 120 mg tablet twice a day for 4 weeks (Double-blind phase) for CNE, MC, and AD patients
Placebo (MC)
Placebo 1 tablet twice a day for 4 weeks for CNE, MC and AD patients
Change in Cognitive Tests-MMSE Score in MC and CNE Groups
0.00 MMSE Score
Interval -4.0 to 2.0
0.00 MMSE Score
Interval -5.0 to 4.0

SECONDARY outcome

Timeframe: From Baseline (Month 0) to Month 18

Population: ITT population. N=Number of subjects with assessment.

Clock drawing test is a visuo-constructive task, where subjects are asked to draw the face of a clock in a pre-drawn circle and then to draw in the arms to denote 16:45 (a quarter to five). The drawing can then be evaluated by a quantitative scoring method, which is based on the degree of completion of the drawing. The scoring system ranges from 0 to 6 with higher scores reflecting a greater number of errors and more impairment.

Outcome measures

Outcome measures
Measure
EGb 120 mg (Open Phase - CNE)
n=19 Participants
EGb761 120 mg tablet twice a day for 17 months (open phase) for CNE patients
EGb 120 mg (Open Phase - MC)
n=12 Participants
EGb761 120 mg 17 months (open phase) for MC patients
EGb761 120 mg (MC)
EGb761 120 mg tablet twice a day for 4 weeks (Double-blind phase) for CNE, MC, and AD patients
Placebo (MC)
Placebo 1 tablet twice a day for 4 weeks for CNE, MC and AD patients
Change in Cognitive Tests-Clock Drawing Test Score in MC and CNE Groups
0.00 Clock drawing test score
Interval -4.0 to 1.0
0.00 Clock drawing test score
Interval -3.0 to 2.0

SECONDARY outcome

Timeframe: From Baseline (Month 0) to Month 18

Population: ITT population. N=Number of subjects with assessment.

Cube drawing: Subjects are asked to draw a cube by heart. In case of failure, a model of a cube is given to the subjects to copy. The score system ranges from 0 (worse score) to 6 (best score). Score calculation is following: 1 point by face with 4 sides, 2 points for each face where each angle should be respected.

Outcome measures

Outcome measures
Measure
EGb 120 mg (Open Phase - CNE)
n=19 Participants
EGb761 120 mg tablet twice a day for 17 months (open phase) for CNE patients
EGb 120 mg (Open Phase - MC)
n=12 Participants
EGb761 120 mg 17 months (open phase) for MC patients
EGb761 120 mg (MC)
EGb761 120 mg tablet twice a day for 4 weeks (Double-blind phase) for CNE, MC, and AD patients
Placebo (MC)
Placebo 1 tablet twice a day for 4 weeks for CNE, MC and AD patients
Change in Cognitive Tests-Cube Drawing Test Score in MC and CNE Groups
0.00 Cube drawing test score
Interval -6.0 to 2.0
0.00 Cube drawing test score
Interval -4.0 to 2.0

SECONDARY outcome

Timeframe: From Baseline (Month 0) to Month 18

Population: ITT population. N=Number of subjects with assessment.

Free and Cued Selective Reminding Test (FCSRT) Assessment of verbal episodic memory. By this test performances in free recalls, cued recalls and in a recognition task can be analysed, because the process of encoding is controlled. Subjects are asked to remember a list of 16 words. Three tasks of free and cued recalls, as well as one recognition task and one delayed recall give the scores. Total recall is obtained by the addition of cued recalls to free recalls. Maximum score is 48 for immediate: 16 words X 3 corresponding to immediate free recall + immediate cued recall + immediate recognition test. Maximum score is 64 (better score) when delayed recall : 16 words X 4 . The minimum score is 0 (worse).

Outcome measures

Outcome measures
Measure
EGb 120 mg (Open Phase - CNE)
n=19 Participants
EGb761 120 mg tablet twice a day for 17 months (open phase) for CNE patients
EGb 120 mg (Open Phase - MC)
n=12 Participants
EGb761 120 mg 17 months (open phase) for MC patients
EGb761 120 mg (MC)
EGb761 120 mg tablet twice a day for 4 weeks (Double-blind phase) for CNE, MC, and AD patients
Placebo (MC)
Placebo 1 tablet twice a day for 4 weeks for CNE, MC and AD patients
Change in Cognitive Tests in MC and CNE Groups - Total Immediate Recall and Delayed Recall Scores of FCSRT
Total Immediate Recall Score of FCSRT
2.00 Recall score
Interval -3.0 to 16.0
1.50 Recall score
Interval -4.0 to 8.0
Change in Cognitive Tests in MC and CNE Groups - Total Immediate Recall and Delayed Recall Scores of FCSRT
Total Delayed Recall Score of FCSRT
0.00 Recall score
Interval -6.0 to 6.0
0.00 Recall score
Interval -2.0 to 2.0

SECONDARY outcome

Timeframe: From Baseline (Month 0) to Month 18

Population: ITT population. N=Number of subjects with assessment.

Subjects are asked to memorize two short stories, one consisting of 24, the other one of 26 information units. After the stories have been read aloud by the investigator, subjects are asked to enounce all items of information they can remember (free recall). Correctly reported items are added for each story. This test applies analytical capacities, as well as auditive and verbal synthesis, working memory and episodic memory. Score range from 0(worst) to 75 (better).

Outcome measures

Outcome measures
Measure
EGb 120 mg (Open Phase - CNE)
n=19 Participants
EGb761 120 mg tablet twice a day for 17 months (open phase) for CNE patients
EGb 120 mg (Open Phase - MC)
n=11 Participants
EGb761 120 mg 17 months (open phase) for MC patients
EGb761 120 mg (MC)
EGb761 120 mg tablet twice a day for 4 weeks (Double-blind phase) for CNE, MC, and AD patients
Placebo (MC)
Placebo 1 tablet twice a day for 4 weeks for CNE, MC and AD patients
Change in Cognitive Tests-Age-Adjusted Logical Memory (MEM III) in MC and CNE Groups
0.00 Age adjusted score
Interval -4.0 to 7.0
0.00 Age adjusted score
Interval -4.0 to 9.0

SECONDARY outcome

Timeframe: From Baseline (Month 0) to Month 18

Population: ITT population. N=Number of subjects with assessment.

Wechsler Adult Intelligence Scale (WAIS) In this test subjects are asked to say how two seemingly dissimilar items might in fact be similar (14 item couples). This test involves especially abstract thinking and concept capacities. Cognitive Tests-Age-Adjusted Wechsler Adult Intelligence Scale (WAIS): 19 tests on similarities. The items 1 to 5 are graded from 1 (good) to 0 (bad), and the items 6 to 19 are graded from 2 (good) to 0 (bad). Item 6 and 7 can be repeated. At the end, the worst total score is 0, the best total score is 33.

Outcome measures

Outcome measures
Measure
EGb 120 mg (Open Phase - CNE)
n=19 Participants
EGb761 120 mg tablet twice a day for 17 months (open phase) for CNE patients
EGb 120 mg (Open Phase - MC)
n=12 Participants
EGb761 120 mg 17 months (open phase) for MC patients
EGb761 120 mg (MC)
EGb761 120 mg tablet twice a day for 4 weeks (Double-blind phase) for CNE, MC, and AD patients
Placebo (MC)
Placebo 1 tablet twice a day for 4 weeks for CNE, MC and AD patients
Change in Cognitive Tests-Age-Adjusted WAIS in MC and CNE Groups
1.00 Age adjusted score
Interval -3.0 to 4.0
1.50 Age adjusted score
Interval -2.0 to 5.0

SECONDARY outcome

Timeframe: From Baseline (Month 0) to Month 18

Population: ITT population. N=Number of subjects with assessment.

TMT is a neuropsychological test of visual attention and task switching. The task requires a subject to 'connect-the-dots' of 25 consecutive numbers (1,2,3,etc.) on a sheet of paper or computer screen. The goal of the subject is to finish the test as quickly as possible and the time taken to complete the test is used as the primary performance metric (in seconds). The maximum time allowed is 300 seconds. A negative change score indicates improvement. First, in the TMT A, the subject has to connect numbers increasingly as fast as possible.The TMT B requires the subject to connect and letters in an alternating pattern (1-A-2-B-3-C, etc.) in as little time as possible.

Outcome measures

Outcome measures
Measure
EGb 120 mg (Open Phase - CNE)
n=21 Participants
EGb761 120 mg tablet twice a day for 17 months (open phase) for CNE patients
EGb 120 mg (Open Phase - MC)
n=20 Participants
EGb761 120 mg 17 months (open phase) for MC patients
EGb761 120 mg (MC)
EGb761 120 mg tablet twice a day for 4 weeks (Double-blind phase) for CNE, MC, and AD patients
Placebo (MC)
Placebo 1 tablet twice a day for 4 weeks for CNE, MC and AD patients
Change in Cognitive Tests-Time to Perform TMT in MC and CNE Groups
Task A (N=18,12)
-3.00 Seconds
Interval -59.0 to 8.0
-1.00 Seconds
Interval -31.0 to 29.0
Change in Cognitive Tests-Time to Perform TMT in MC and CNE Groups
Task B (N=18,11)
-4.50 Seconds
Interval -213.0 to 29.0
-9.00 Seconds
Interval -76.0 to 100.0

SECONDARY outcome

Timeframe: At Month 18

Population: ITT population. N=Number of subjects with assessment.

The Diagnostic and Statistical Manual of Mental Disorders: 4th Edition of the American Psychiatric Association (DSM-IV, 1994) also outlines diagnostic criteria for dementia of the Alzheimer's type that are generally consistent with the NINCDS-ADRDA criteria.

Outcome measures

Outcome measures
Measure
EGb 120 mg (Open Phase - CNE)
n=21 Participants
EGb761 120 mg tablet twice a day for 17 months (open phase) for CNE patients
EGb 120 mg (Open Phase - MC)
n=20 Participants
EGb761 120 mg 17 months (open phase) for MC patients
EGb761 120 mg (MC)
EGb761 120 mg tablet twice a day for 4 weeks (Double-blind phase) for CNE, MC, and AD patients
Placebo (MC)
Placebo 1 tablet twice a day for 4 weeks for CNE, MC and AD patients
Number of Subjects Conversion to Alzheimer's Dementia Diagnosed According to the DSM IV (Diagnostic of Dementia)
0 participants
0 participants

SECONDARY outcome

Timeframe: At Month 18

Population: ITT population. N=Number of subjects with assessment.

The most widely accepted diagnostic criteria for probable AD are those offered by the National Institute of Neurological and Communicative Disorders and Stroke and by the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA; McKhann et al., 1984). These criteria include the presence of dementia established by clinical examination and confirmed by neuropsychological testing. The dementia is described as involving multiple, progressive cognitive deficits in older persons in the absence of disturbances of consciousness, presence of psychoactive substances, or any other medical, neurological, or psychiatric conditions that might in and of themselves account for these progressive deficits.

Outcome measures

Outcome measures
Measure
EGb 120 mg (Open Phase - CNE)
n=21 Participants
EGb761 120 mg tablet twice a day for 17 months (open phase) for CNE patients
EGb 120 mg (Open Phase - MC)
n=20 Participants
EGb761 120 mg 17 months (open phase) for MC patients
EGb761 120 mg (MC)
EGb761 120 mg tablet twice a day for 4 weeks (Double-blind phase) for CNE, MC, and AD patients
Placebo (MC)
Placebo 1 tablet twice a day for 4 weeks for CNE, MC and AD patients
Number of Subjects Conversion to Alzheimer's Dementia Diagnosed According to NINCDS-ADRDA (Diagnostic of Alzheimer's)
0 participants
0 participants

SECONDARY outcome

Timeframe: Up to Month 18

Population: Safety population. CNE patients withdrew during the double-blind phase and were also not included in the safety population for open phase (17 months).

The relationship of an adverse event to the study medication will be classified according to the following criteria: Related : reports including good reasons and sufficient information (e.g. temporal relationship, dose-response relationship, pharmacology, positive de-challenge and/or re-challenge) to assume a causal relationship with the study drug in the sense that it is plausible, conceivable, or likely Not related: reports including good reasons and sufficient information (e.g. no temporal relationship and/or attributable to concurrent disease or other drugs) to rule out a causal relationship with the study drug.

Outcome measures

Outcome measures
Measure
EGb 120 mg (Open Phase - CNE)
n=23 Participants
EGb761 120 mg tablet twice a day for 17 months (open phase) for CNE patients
EGb 120 mg (Open Phase - MC)
n=26 Participants
EGb761 120 mg 17 months (open phase) for MC patients
EGb761 120 mg (MC)
n=41 Participants
EGb761 120 mg tablet twice a day for 4 weeks (Double-blind phase) for CNE, MC, and AD patients
Placebo (MC)
Placebo 1 tablet twice a day for 4 weeks for CNE, MC and AD patients
Incidence of Adverse Events (AEs)
Any Adverse Events
5 participants
9 participants
25 participants
Incidence of Adverse Events (AEs)
Any Treatment Emergent
5 participants
8 participants
25 participants
Incidence of Adverse Events (AEs)
Intensity of Severe Treatment Emergent AEs (TEAEs)
1 participants
0 participants
6 participants
Incidence of Adverse Events (AEs)
Intensity of moderate TEAEs
2 participants
4 participants
14 participants
Incidence of Adverse Events (AEs)
Intensity of mild TEAEs
4 participants
5 participants
20 participants
Incidence of Adverse Events (AEs)
Causality of Related TEAEs
1 participants
2 participants
3 participants
Incidence of Adverse Events (AEs)
Causality of Non Related TEAEs
4 participants
6 participants
25 participants
Incidence of Adverse Events (AEs)
Causality and Intensity
0 participants
0 participants
0 participants
Incidence of Adverse Events (AEs)
At least one related & severe
0 participants
0 participants
0 participants
Incidence of Adverse Events (AEs)
At least one related & moderate
0 participants
1 participants
1 participants
Incidence of Adverse Events (AEs)
At least one related & mild
1 participants
2 participants
2 participants
Incidence of Adverse Events (AEs)
At least one not related & severe
1 participants
0 participants
6 participants
Incidence of Adverse Events (AEs)
At least one not related & moderate
2 participants
3 participants
14 participants
Incidence of Adverse Events (AEs)
At least one not related & mild
3 participants
3 participants
20 participants
Incidence of Adverse Events (AEs)
TEAEs leading to withdrawal
1 participants
2 participants
4 participants
Incidence of Adverse Events (AEs)
TEAES Leading to Death
0 participants
0 participants
0 participants
Incidence of Adverse Events (AEs)
Serious AEs (SAEs)
1 participants
0 participants
6 participants
Incidence of Adverse Events (AEs)
Non SAEs
5 participants
9 participants
23 participants

SECONDARY outcome

Timeframe: From Baseline (Month 0) to Month 18

Population: ITT population.

Evolution of brain morphology (degree of cortical atrophy) after 18 months with EGb761, using MRI voxel based morphometry

Outcome measures

Outcome measures
Measure
EGb 120 mg (Open Phase - CNE)
n=21 Participants
EGb761 120 mg tablet twice a day for 17 months (open phase) for CNE patients
EGb 120 mg (Open Phase - MC)
n=20 Participants
EGb761 120 mg 17 months (open phase) for MC patients
EGb761 120 mg (MC)
EGb761 120 mg tablet twice a day for 4 weeks (Double-blind phase) for CNE, MC, and AD patients
Placebo (MC)
Placebo 1 tablet twice a day for 4 weeks for CNE, MC and AD patients
Change in Brain Morphology in the MC and CNE Groups as Determined by the Change in Voxel Size
Cerebellum
6454.00 mm3
Interval -42470.0 to 30372.0
6168.50 mm3
Interval -38855.2 to 65345.0
Change in Brain Morphology in the MC and CNE Groups as Determined by the Change in Voxel Size
Left cerebral cortex
5765.50 mm3
Interval -52347.0 to 97071.0
32428.00 mm3
Interval -103527.0 to 88300.0
Change in Brain Morphology in the MC and CNE Groups as Determined by the Change in Voxel Size
Left thalamus
145.20 mm3
Interval -418.9 to 1023.1
24.57 mm3
Interval -794.8 to 780.4
Change in Brain Morphology in the MC and CNE Groups as Determined by the Change in Voxel Size
Left caudate nucleus
154.68 mm3
Interval -387.3 to 1105.3
140.97 mm3
Interval -827.2 to 1384.0
Change in Brain Morphology in the MC and CNE Groups as Determined by the Change in Voxel Size
Left putamen nucleus
-17.14 mm3
Interval -346.4 to 676.4
4.00 mm3
Interval -842.6 to 481.0
Change in Brain Morphology in the MC and CNE Groups as Determined by the Change in Voxel Size
Left ventral striatum
65.26 mm3
Interval -99.0 to 157.6
81.56 mm3
Interval -57.4 to 236.4
Change in Brain Morphology in the MC and CNE Groups as Determined by the Change in Voxel Size
Left globus pallidus
104.75 mm3
Interval -86.2 to 380.4
50.66 mm3
Interval -208.7 to 431.8
Change in Brain Morphology in the MC and CNE Groups as Determined by the Change in Voxel Size
Right cerebral cortex
5853.00 mm3
Interval -40148.0 to 103200.0
38955.50 mm3
Interval -102169.0 to 97667.0
Change in Brain Morphology in the MC and CNE Groups as Determined by the Change in Voxel Size
Right thalamus
144.83 mm3
Interval -715.7 to 669.6
14.90 mm3
Interval -570.1 to 755.1
Change in Brain Morphology in the MC and CNE Groups as Determined by the Change in Voxel Size
Right caudate nucleus
228.74 mm3
Interval -274.2 to 519.6
303.66 mm3
Interval -223.5 to 1084.4
Change in Brain Morphology in the MC and CNE Groups as Determined by the Change in Voxel Size
Right putamen nucleus
8.36 mm3
Interval -229.6 to 663.8
-78.94 mm3
Interval -520.5 to 343.9
Change in Brain Morphology in the MC and CNE Groups as Determined by the Change in Voxel Size
Right ventral striatum
65.15 mm3
Interval -5.5 to 198.8
70.85 mm3
Interval -13.0 to 287.7
Change in Brain Morphology in the MC and CNE Groups as Determined by the Change in Voxel Size
Right globus pallidus
84.68 mm3
Interval -293.0 to 312.6
64.82 mm3
Interval -119.3 to 318.8

Adverse Events

EGb761 120 mg (Double-blind Phase)

Serious events: 1 serious events
Other events: 5 other events
Deaths: 0 deaths

Placebo (Double-blind Phase)

Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths

EGb761 120 mg (Open Phase)

Serious events: 6 serious events
Other events: 23 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
EGb761 120 mg (Double-blind Phase)
n=23 participants at risk
EGb761 120 mg tablet twice a day for 4 weeks (double-blind phase) for CNE, MC, and AD patients
Placebo (Double-blind Phase)
n=26 participants at risk
Placebo 1 tablet twice a day for 4 weeks (double-blind phase) for CNE, MC, and AD patients
EGb761 120 mg (Open Phase)
n=41 participants at risk
EGb761 120 mg tablet twice a day for 17 months (open phase) for MC and CNE patients
Nervous system disorders
Transient ischaemic attack
4.3%
1/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
0.00%
0/41 • Up to month 18 follow up
Cardiac disorders
Atrial fibrillation
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Hepatobiliary disorders
Cholelithiasis
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Nervous system disorders
Sciatica
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Nervous system disorders
Spinal cord compression
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Vascular disorders
Subclavian artery stenosis
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up

Other adverse events

Other adverse events
Measure
EGb761 120 mg (Double-blind Phase)
n=23 participants at risk
EGb761 120 mg tablet twice a day for 4 weeks (double-blind phase) for CNE, MC, and AD patients
Placebo (Double-blind Phase)
n=26 participants at risk
Placebo 1 tablet twice a day for 4 weeks (double-blind phase) for CNE, MC, and AD patients
EGb761 120 mg (Open Phase)
n=41 participants at risk
EGb761 120 mg tablet twice a day for 17 months (open phase) for MC and CNE patients
Gastrointestinal disorders
Constipation
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
7.3%
3/41 • Up to month 18 follow up
Gastrointestinal disorders
Gastro esophageal reflux disease
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
4.9%
2/41 • Up to month 18 follow up
Gastrointestinal disorders
Aerophagia
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Gastrointestinal disorders
Nausea
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Gastrointestinal disorders
Food poisoning
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Gastrointestinal disorders
Gastrointestinal disorder
0.00%
0/23 • Up to month 18 follow up
3.8%
1/26 • Up to month 18 follow up
0.00%
0/41 • Up to month 18 follow up
Gastrointestinal disorders
Vomiting
4.3%
1/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
0.00%
0/41 • Up to month 18 follow up
Nervous system disorders
Dementia Alzheimer's type
0.00%
0/23 • Up to month 18 follow up
3.8%
1/26 • Up to month 18 follow up
4.9%
2/41 • Up to month 18 follow up
Nervous system disorders
Headache
4.3%
1/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Nervous system disorders
Essential Tremor
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Nervous system disorders
Dizziness
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Nervous system disorders
Hemicephalalgia
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Nervous system disorders
Neuralgia
0.00%
0/23 • Up to month 18 follow up
3.8%
1/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Nervous system disorders
Syncope vasovagal
0.00%
0/23 • Up to month 18 follow up
3.8%
1/26 • Up to month 18 follow up
0.00%
0/41 • Up to month 18 follow up
Infections and infestations
Bronchitis
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
4.9%
2/41 • Up to month 18 follow up
Infections and infestations
Pharyngitis
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Infections and infestations
Urinary tract infection
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Infections and infestations
Bronchopneumonia
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Infections and infestations
Ear infection
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Infections and infestations
Gastroenteritis viral
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Infections and infestations
Herpes zoster
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Infections and infestations
Tracheobronchitis
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Skin and subcutaneous tissue disorders
Dry skin
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Skin and subcutaneous tissue disorders
Pigmentation disorder
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Skin and subcutaneous tissue disorders
Rash
0.00%
0/23 • Up to month 18 follow up
3.8%
1/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Skin and subcutaneous tissue disorders
Dermal cyst
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Psychiatric disorders
Depression
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
7.3%
3/41 • Up to month 18 follow up
Psychiatric disorders
Insomnia
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
7.3%
3/41 • Up to month 18 follow up
Psychiatric disorders
Anxiety
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Psychiatric disorders
Delirium
4.3%
1/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
0.00%
0/41 • Up to month 18 follow up
Injury, poisoning and procedural complications
Fall
4.3%
1/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
12.2%
5/41 • Up to month 18 follow up
Injury, poisoning and procedural complications
Spinal fracture
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Injury, poisoning and procedural complications
Wound
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Injury, poisoning and procedural complications
Procedural nausea
0.00%
0/23 • Up to month 18 follow up
3.8%
1/26 • Up to month 18 follow up
0.00%
0/41 • Up to month 18 follow up
Cardiac disorders
Palpitations
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Cardiac disorders
Tachycardia
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Respiratory, thoracic and mediastinal disorders
Dyspnoea
0.00%
0/23 • Up to month 18 follow up
7.7%
2/26 • Up to month 18 follow up
4.9%
2/41 • Up to month 18 follow up
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Musculoskeletal and connective tissue disorders
Back pain
0.00%
0/23 • Up to month 18 follow up
7.7%
2/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Musculoskeletal and connective tissue disorders
Arthralgia
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
4.9%
2/41 • Up to month 18 follow up
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Musculoskeletal and connective tissue disorders
Neck pain
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Musculoskeletal and connective tissue disorders
Tendonitis
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Musculoskeletal and connective tissue disorders
Myalgia
0.00%
0/23 • Up to month 18 follow up
3.8%
1/26 • Up to month 18 follow up
0.00%
0/41 • Up to month 18 follow up
General disorders
Asthenia
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
General disorders
Fatigue
4.3%
1/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
General disorders
Oedema peripheral
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Ear and labyrinth disorders
Vertigo
0.00%
0/23 • Up to month 18 follow up
3.8%
1/26 • Up to month 18 follow up
4.9%
2/41 • Up to month 18 follow up
Eye disorders
Macular degeneration
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Eye disorders
Vision blurred
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Eye disorders
Cataract
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Renal and urinary disorders
Urinary incontinence
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Renal and urinary disorders
Renal colic
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Vascular disorders
Orthostatic hypotension
4.3%
1/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Vascular disorders
Haematoma
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Vascular disorders
Hypertension
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Metabolism and nutrition disorders
Hypercholesterolaemia
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Reproductive system and breast disorders
Benign prostatic hyperplasia
0.00%
0/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
2.4%
1/41 • Up to month 18 follow up
Gastrointestinal disorders
Diarrhoea
4.3%
1/23 • Up to month 18 follow up
0.00%
0/26 • Up to month 18 follow up
4.9%
2/41 • Up to month 18 follow up

Additional Information

Medical Director, Neurology

Ipsen

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place