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

Primary Purpose

Alzheimer's Disease, Cognitive Impairment

Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
EGb761®
Placebo
Sponsored by
Ipsen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer's Disease focused on measuring Mild Alzheimer's disease (AD) patients, Memory complaint patients with cognitive impairment (MC), Memory complaint patients cognitively normal (CNE)

Eligibility Criteria

65 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Group Specific Inclusion Criteria:

Cognitively normal elderly (CNE)

  • Spontaneous memory complaint by patient,
  • Mini-Mental State Exam score ≥ 28.
  • Clinical Dementia Rating = 0.
  • No Diagnostic And Statistical Manual Of Mental Disorders, Fourth Edition (DSMIV) criteria for Dementia.

Memory complaints (MC) :

  • Spontaneous memory complaint by patient
  • Mini-Mental State Exam score ≥ 25
  • Clinical Dementia Rating 0.5.
  • No DSMIV criteria for Dementia.

Mild Alzheimer's Disease (AD):

  • Mini Mental Status Examination (MMSE) between 20 and 28 (inclusive).
  • Clinical Dementia Rating ≥ 1.0
  • DSMIV criteria for Dementia.
  • National Institute of Neurological and Communicative Diseases and Stroke / Alzheimer's Disease and Related Disorders Association(NINCDS/ADRDA) criteria for probable AD.
  • Newly diagnosed patients without treatment by Cholinesterase Inhibitors or Memantine.
  • ≥ 65 years of age, both sex
  • Geriatric Depression Scale (GDS) < 15
  • Informed consent signed by the patient or, if necessary by legal representative

Exclusion Criteria:

  • Contraindication to Magnetic Resonance Imaging (MRI) and/or Positron-Emission Tomography (PET) scan
  • Forbidden Concomitant medications (Cholinesterase inhibitors and memantine, Specific psychoactive medications,e.g., neuroleptics, chronic anxiolytics including meprobamate, or sedative hypnotics other than benzodiazepines, Monoamine oxidase inhibitors (MAOIs) including selective MAOIs. Drugs acting on cerebral nervous system, Antidiabetes medications , Antioxidants medications, Medications known to interfere with cognitive evaluations
  • Significant neurological disease and psychiatric disorders/psychotic feature
  • Significant medical illness

Sites / Locations

  • Hôpital Corentin Celton 4 parvis Corentin Celton
  • Hôpital de Juvisy
  • CMPI "Les Rives de Seine"
  • Centre Hospitalier d'Orsay 4 place du Général Leclerc
  • Private practice
  • Hôpital Broca 54-56 rue Pascal
  • Observatoire de l'âge
  • Hôpital Paul Brousse 12 av Paul-Vaillant-Couturier

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

EGb 120 mg

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Change in Brain Glucose Metabolism Measured Using 18-Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET)
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)

Secondary Outcome Measures

Change in Brain Glucose Metabolism in the MC and CNE Groups
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
Change in Cognitive Tests-Clinical Dementia Rating (CDR) Score in MC and CNE Groups
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).
Change in Cognitive Tests-Geriatric Depression Scale (GDS) Score in MC and CNE Groups
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.
Change in Cognitive Tests-Verbal Fluency in MC and CNE Groups
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.
Change in Cognitive Tests-Mini Mental Status Examination (MMSE) Score in MC and CNE Groups
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.
Change in Cognitive Tests-Clock Drawing Test Score in MC and CNE Groups
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.
Change in Cognitive Tests-Cube Drawing Test Score in MC and CNE Groups
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.
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)
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).
Change in Cognitive Tests-Age-Adjusted Logical Memory (MEM III) in MC and CNE Groups
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).
Change in Cognitive Tests-Age-Adjusted Wechsler Adult Intelligence Scale (WAIS) in MC and CNE Groups
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.
Change in Cognitive Tests-Time to Perform Trail Making Test (TMT) in MC and CNE Groups
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.
Number of Subjects Conversion to Alzheimer's Dementia Diagnosed According to the DSM IV (Diagnostic of Dementia)
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)
Number of Subjects Conversion to Alzheimer's Dementia Diagnosed According to NINCDS-ADRDA (Diagnostic of Alzheimer's)
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.
Change in Cognitive Tests-CDR Score in MC and CNE Groups
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)
Change in Cognitive Tests-GDS Score in MC and CNE Groups
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.
Change in Cognitive Tests-Verbal Fluency in MC and CNE Groups
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.
Change in Cognitive Tests-MMSE Score in MC and CNE Groups
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.
Change in Cognitive Tests-Clock Drawing Test Score in MC and CNE Groups
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.
Change in Cognitive Tests-Cube Drawing Test Score in MC and CNE Groups
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.
Change in Cognitive Tests in MC and CNE Groups - Total Immediate Recall and Delayed Recall Scores of FCSRT
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).
Change in Cognitive Tests-Age-Adjusted Logical Memory (MEM III) in MC and CNE Groups
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).
Change in Cognitive Tests-Age-Adjusted WAIS in MC and CNE Groups
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.
Change in Cognitive Tests-Time to Perform TMT in MC and CNE Groups
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.
Number of Subjects Conversion to Alzheimer's Dementia Diagnosed According to the DSM IV (Diagnostic of Dementia)
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.
Number of Subjects Conversion to Alzheimer's Dementia Diagnosed According to NINCDS-ADRDA (Diagnostic of Alzheimer's)
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.
Incidence of Adverse Events (AEs)
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.
Change in Brain Morphology in the MC and CNE Groups as Determined by the Change in Voxel Size
Evolution of brain morphology (degree of cortical atrophy) after 18 months with EGb761, using MRI voxel based morphometry

Full Information

First Posted
December 23, 2008
Last Updated
January 24, 2019
Sponsor
Ipsen
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1. Study Identification

Unique Protocol Identification Number
NCT00814346
Brief Title
Effect of EGb761® on Brain Glucose Metabolism in Three Groups of Elderly Defined by Cognitive Functions
Official Title
Effect of Oral EGb761® on Brain Glucose Metabolism in Three Groups of Elderly With Memory Complaint, Mild Alzheimer's Disease, and Cognitively Normal Elderly. Phase II, Randomised, Double-blind, Parallel Groups, Placebo-controlled Study
Study Type
Interventional

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Completed
Study Start Date
October 2008 (undefined)
Primary Completion Date
July 2012 (Actual)
Study Completion Date
July 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ipsen

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The aim of the study is to evaluate the effect of EGb761®, in comparison to placebo, on cerebral glucose metabolism, in three groups of elderly patients: newly diagnosed mild Alzheimer's disease (AD), memory complaint patients with cognitive impairment (MC) and memory complaint patients cognitively normal (CNE). The first phase includes four weeks treatment with EGb761® for all groups, with change in brain glucose metabolism at month 1 using 18 FDG-PET, as primary endpoint which will be followed by an open 17 months follow-up (FU) period with EGb761® treatment in MC and CNE patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease, Cognitive Impairment
Keywords
Mild Alzheimer's disease (AD) patients, Memory complaint patients with cognitive impairment (MC), Memory complaint patients cognitively normal (CNE)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
49 (Actual)

8. Arms, Groups, and Interventions

Arm Title
EGb 120 mg
Arm Type
Active Comparator
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
EGb761®
Intervention Description
Four weeks for AD patients, 18 months for MC and CNE patients
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo 1 tablet BID
Primary Outcome Measure Information:
Title
Change in Brain Glucose Metabolism Measured Using 18-Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET)
Description
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)
Time Frame
From Baseline (Month 0) to Week 4 (Month 1) - Double blind phase
Secondary Outcome Measure Information:
Title
Change in Brain Glucose Metabolism in the MC and CNE Groups
Description
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
Time Frame
From Baseline (Month 0) to Month 18
Title
Change in Cognitive Tests-Clinical Dementia Rating (CDR) Score in MC and CNE Groups
Description
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).
Time Frame
From Baseline (Month 0) to Month 9
Title
Change in Cognitive Tests-Geriatric Depression Scale (GDS) Score in MC and CNE Groups
Description
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.
Time Frame
From Baseline (Month 0) to Month 9
Title
Change in Cognitive Tests-Verbal Fluency in MC and CNE Groups
Description
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.
Time Frame
From Baseline (Month 0) to Month 9
Title
Change in Cognitive Tests-Mini Mental Status Examination (MMSE) Score in MC and CNE Groups
Description
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.
Time Frame
From Baseline (Month 0) to Month 9
Title
Change in Cognitive Tests-Clock Drawing Test Score in MC and CNE Groups
Description
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.
Time Frame
From Baseline (Month 0) to Month 9
Title
Change in Cognitive Tests-Cube Drawing Test Score in MC and CNE Groups
Description
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.
Time Frame
From Baseline (Month 0) to Month 9
Title
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)
Description
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).
Time Frame
From Baseline (Month 0) to Month 9
Title
Change in Cognitive Tests-Age-Adjusted Logical Memory (MEM III) in MC and CNE Groups
Description
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).
Time Frame
From Baseline (Month 0) to Month 9
Title
Change in Cognitive Tests-Age-Adjusted Wechsler Adult Intelligence Scale (WAIS) in MC and CNE Groups
Description
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.
Time Frame
From Baseline (Month 0) to Month 9
Title
Change in Cognitive Tests-Time to Perform Trail Making Test (TMT) in MC and CNE Groups
Description
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.
Time Frame
From Baseline (Month 0) to Month 9
Title
Number of Subjects Conversion to Alzheimer's Dementia Diagnosed According to the DSM IV (Diagnostic of Dementia)
Description
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)
Time Frame
At Month 9
Title
Number of Subjects Conversion to Alzheimer's Dementia Diagnosed According to NINCDS-ADRDA (Diagnostic of Alzheimer's)
Description
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.
Time Frame
At Month 9
Title
Change in Cognitive Tests-CDR Score in MC and CNE Groups
Description
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)
Time Frame
From Baseline (Month 0) to Month 18
Title
Change in Cognitive Tests-GDS Score in MC and CNE Groups
Description
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.
Time Frame
From Baseline (Month 0) to Month 18
Title
Change in Cognitive Tests-Verbal Fluency in MC and CNE Groups
Description
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.
Time Frame
From Baseline (Month 0) to Month 18
Title
Change in Cognitive Tests-MMSE Score in MC and CNE Groups
Description
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.
Time Frame
From Baseline (Month 0) to Month 18
Title
Change in Cognitive Tests-Clock Drawing Test Score in MC and CNE Groups
Description
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.
Time Frame
From Baseline (Month 0) to Month 18
Title
Change in Cognitive Tests-Cube Drawing Test Score in MC and CNE Groups
Description
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.
Time Frame
From Baseline (Month 0) to Month 18
Title
Change in Cognitive Tests in MC and CNE Groups - Total Immediate Recall and Delayed Recall Scores of FCSRT
Description
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).
Time Frame
From Baseline (Month 0) to Month 18
Title
Change in Cognitive Tests-Age-Adjusted Logical Memory (MEM III) in MC and CNE Groups
Description
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).
Time Frame
From Baseline (Month 0) to Month 18
Title
Change in Cognitive Tests-Age-Adjusted WAIS in MC and CNE Groups
Description
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.
Time Frame
From Baseline (Month 0) to Month 18
Title
Change in Cognitive Tests-Time to Perform TMT in MC and CNE Groups
Description
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.
Time Frame
From Baseline (Month 0) to Month 18
Title
Number of Subjects Conversion to Alzheimer's Dementia Diagnosed According to the DSM IV (Diagnostic of Dementia)
Description
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.
Time Frame
At Month 18
Title
Number of Subjects Conversion to Alzheimer's Dementia Diagnosed According to NINCDS-ADRDA (Diagnostic of Alzheimer's)
Description
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.
Time Frame
At Month 18
Title
Incidence of Adverse Events (AEs)
Description
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.
Time Frame
Up to Month 18
Title
Change in Brain Morphology in the MC and CNE Groups as Determined by the Change in Voxel Size
Description
Evolution of brain morphology (degree of cortical atrophy) after 18 months with EGb761, using MRI voxel based morphometry
Time Frame
From Baseline (Month 0) to Month 18

10. Eligibility

Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Group Specific Inclusion Criteria: Cognitively normal elderly (CNE) Spontaneous memory complaint by patient, Mini-Mental State Exam score ≥ 28. Clinical Dementia Rating = 0. No Diagnostic And Statistical Manual Of Mental Disorders, Fourth Edition (DSMIV) criteria for Dementia. Memory complaints (MC) : Spontaneous memory complaint by patient Mini-Mental State Exam score ≥ 25 Clinical Dementia Rating 0.5. No DSMIV criteria for Dementia. Mild Alzheimer's Disease (AD): Mini Mental Status Examination (MMSE) between 20 and 28 (inclusive). Clinical Dementia Rating ≥ 1.0 DSMIV criteria for Dementia. National Institute of Neurological and Communicative Diseases and Stroke / Alzheimer's Disease and Related Disorders Association(NINCDS/ADRDA) criteria for probable AD. Newly diagnosed patients without treatment by Cholinesterase Inhibitors or Memantine. ≥ 65 years of age, both sex Geriatric Depression Scale (GDS) < 15 Informed consent signed by the patient or, if necessary by legal representative Exclusion Criteria: Contraindication to Magnetic Resonance Imaging (MRI) and/or Positron-Emission Tomography (PET) scan Forbidden Concomitant medications (Cholinesterase inhibitors and memantine, Specific psychoactive medications,e.g., neuroleptics, chronic anxiolytics including meprobamate, or sedative hypnotics other than benzodiazepines, Monoamine oxidase inhibitors (MAOIs) including selective MAOIs. Drugs acting on cerebral nervous system, Antidiabetes medications , Antioxidants medications, Medications known to interfere with cognitive evaluations Significant neurological disease and psychiatric disorders/psychotic feature Significant medical illness
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ipsen Medical Director
Organizational Affiliation
Ipsen
Official's Role
Study Director
Facility Information:
Facility Name
Hôpital Corentin Celton 4 parvis Corentin Celton
City
Issy-Les-Moulineaux
Country
France
Facility Name
Hôpital de Juvisy
City
Juvisy sur Orge
Country
France
Facility Name
CMPI "Les Rives de Seine"
City
Le Vesinet
Country
France
Facility Name
Centre Hospitalier d'Orsay 4 place du Général Leclerc
City
Orsay
Country
France
Facility Name
Private practice
City
Paris
ZIP/Postal Code
75009
Country
France
Facility Name
Hôpital Broca 54-56 rue Pascal
City
Paris
ZIP/Postal Code
75013
Country
France
Facility Name
Observatoire de l'âge
City
Paris
Country
France
Facility Name
Hôpital Paul Brousse 12 av Paul-Vaillant-Couturier
City
Villejuif
Country
France

12. IPD Sharing Statement

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

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