Clinical trial NCT00814346: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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)
Lead sponsor: Ipsen
Sponsor class: INDUSTRY
First posted: 2008-12-24
Enrollment: 49
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change in Brain Glucose Metabolism Measured Using 18-Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET)
timeFrame: From Baseline (Month 0) to Week 4 (Month 1) - Double blind phase
Secondary outcomes:
measure: Change in Brain Glucose Metabolism in the MC and CNE Groups
timeFrame: From Baseline (Month 0) to Month 18
measure: Change in Cognitive Tests-Clinical Dementia Rating (CDR) Score in MC and CNE Groups
timeFrame: From Baseline (Month 0) to Month 9
measure: Change in Cognitive Tests-Geriatric Depression Scale (GDS) Score in MC and CNE Groups
timeFrame: From Baseline (Month 0) to Month 9
measure: Change in Cognitive Tests-Verbal Fluency in MC and CNE Groups
timeFrame: From Baseline (Month 0) to Month 9
measure: Change in Cognitive Tests-Mini Mental Status Examination (MMSE) Score in MC and CNE Groups
timeFrame: From Baseline (Month 0) to Month 9
measure: Change in Cognitive Tests-Clock Drawing Test Score in MC and CNE Groups
timeFrame: From Baseline (Month 0) to Month 9
measure: Change in Cognitive Tests-Cube Drawing Test Score in MC and CNE Groups
timeFrame: From Baseline (Month 0) to Month 9
measure: 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)
timeFrame: From Baseline (Month 0) to Month 9
measure: Change in Cognitive Tests-Age-Adjusted Logical Memory (MEM III) in MC and CNE Groups
timeFrame: From Baseline (Month 0) to Month 9
measure: Change in Cognitive Tests-Age-Adjusted Wechsler Adult Intelligence Scale (WAIS) in MC and CNE Groups
timeFrame: From Baseline (Month 0) to Month 9
measure: Change in Cognitive Tests-Time to Perform Trail Making Test (TMT) in MC and CNE Groups
timeFrame: From Baseline (Month 0) to Month 9
measure: Number of Subjects Conversion to Alzheimer's Dementia Diagnosed According to the DSM IV (Diagnostic of Dementia)
timeFrame: At Month 9
measure: Number of Subjects Conversion to Alzheimer's Dementia Diagnosed According to NINCDS-ADRDA (Diagnostic of Alzheimer's)
timeFrame: At Month 9
measure: Change in Cognitive Tests-CDR Score in MC and CNE Groups
timeFrame: From Baseline (Month 0) to Month 18
measure: Change in Cognitive Tests-GDS Score in MC and CNE Groups
timeFrame: From Baseline (Month 0) to Month 18
measure: Change in Cognitive Tests-Verbal Fluency in MC and CNE Groups
timeFrame: From Baseline (Month 0) to Month 18
measure: Change in Cognitive Tests-MMSE Score in MC and CNE Groups
timeFrame: From Baseline (Month 0) to Month 18
measure: Change in Cognitive Tests-Clock Drawing Test Score in MC and CNE Groups
timeFrame: From Baseline (Month 0) to Month 18
measure: Change in Cognitive Tests-Cube Drawing Test Score in MC and CNE Groups
timeFrame: From Baseline (Month 0) to Month 18
measure: Change in Cognitive Tests in MC and CNE Groups - Total Immediate Recall and Delayed Recall Scores of FCSRT
timeFrame: From Baseline (Month 0) to Month 18
measure: Change in Cognitive Tests-Age-Adjusted Logical Memory (MEM III) in MC and CNE Groups
timeFrame: From Baseline (Month 0) to Month 18
measure: Change in Cognitive Tests-Age-Adjusted WAIS in MC and CNE Groups
timeFrame: From Baseline (Month 0) to Month 18
measure: Change in Cognitive Tests-Time to Perform TMT in MC and CNE Groups
timeFrame: From Baseline (Month 0) to Month 18
measure: Number of Subjects Conversion to Alzheimer's Dementia Diagnosed According to the DSM IV (Diagnostic of Dementia)
timeFrame: At Month 18
measure: Number of Subjects Conversion to Alzheimer's Dementia Diagnosed According to NINCDS-ADRDA (Diagnostic of Alzheimer's)
timeFrame: At Month 18
measure: Incidence of Adverse Events (AEs)
timeFrame: Up to Month 18
measure: Change in Brain Morphology in the MC and CNE Groups as Determined by the Change in Voxel Size
timeFrame: From Baseline (Month 0) to Month 18
Other outcomes:
Locations:
city: Issy-Les-Moulineaux
country: France
facility: Hôpital Corentin Celton 4 parvis Corentin Celton
city: Juvisy sur Orge
country: France
facility: Hôpital de Juvisy
city: Le Vesinet
country: France
facility: CMPI "Les Rives de Seine"
city: Orsay
country: France
facility: Centre Hospitalier d'Orsay 4 place du Général Leclerc
city: Paris
country: France
facility: Private practice
city: Paris
country: France
facility: Hôpital Broca 54-56 rue Pascal
city: Paris
country: France
facility: Observatoire de l'âge
city: Villejuif
country: France
facility: Hôpital Paul Brousse 12 av Paul-Vaillant-Couturier
Study officials:
affiliation: Ipsen
name: Ipsen Medical Director
role: STUDY_DIRECTOR
References: