Hippocampus Study: Comparative Effect of Donepezil 10mg/d and Placebo on Clinical and Radiological Markers

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00403520
• Date of registration: 21/11/2006
• Prospective Registration: No
• Primary sponsor: Eisai Inc.
• Public title: Hippocampus Study: Comparative Effect of Donepezil 10mg/d and Placebo on Clinical and Radiological Markers
• Scientific title: Assessment of the Comparative Effect of Donepezil 10mg/d and Placebo on Clinical and Radiological Markers in Patients With Mild Cognitive Disorders
• Date of first enrolment: November 2006
• Target sample size: 240
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00403520
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
• Phase: Phase 4

Countries of recruitment

France

Contacts

• Name: Isabelle Tonelli
• Affiliation: Eisai France

Key inclusion & exclusion criteria

Inclusion Criteria (Baseline Visit ("V0"):

1.Men or Women 50 years old or more. 2. Patients with mild cognitive impairment (MCI)
with progressive hippocampal amnestic syndrome, isolated or associated to other cognitive
disorders defined by the Free and cued selective reminding test ( FCSRT ) with Free Recall
< or = 17 OR Total Recall < 40 , according to the Grober and Buschke procedure, modified
according to the results of PREAL study 3.Clinical Dementia Rating (CDR) = 0.5 4. General
cognition and functional performance sufficiently preserved such that a diagnosis of
Possible or Probable Alzheimer's Disease based on Diagnostic and Statistical Manual of
Mental Disorders DSM-IV criteria) cannot be made by the site physician at the time of the
screening visit. This evidence must be fully documented in the subject's study file before
the Randomization visit.

5. Outpatient with an informant person: person from his/her close circle having a regular
weekly contact with the patient and accepting to answer to assessment questionnaires.

6. Visual, hearing capacities (authorized equipment) and oral or written expression,
sufficient for the correct performance of the tests (according to the physician's
opinion).

7. Patient and informant person having signed the written informed consent form.

Exclusion Criteria (Baseline Visit ("V0"):

1. Patients with a contraindication to MRI:

- Pacemaker, cardiac defibrillator or neurostimulator wearers

- Wearers of implanted material activated by an electric, magnetic or mechanical
system

- Wearers of haemostatic clips of intracerebral aneurysms or carotid arteries

- Wearers of cochlear implants

- Patients with an intraocular metallic foreign body

- Claustrophobic patients

- Any other contra-indication to MRI

2. Patients with an evolutive psychiatric pathology and/or unstable according to DSM-IV,
particularly:

- Major depressive episode during the previous 2 years or recurrent depression or
bipolar disorders according to the DSM-IV and/or score >= 12 according to the
17-items depressive Hamilton's Scale

- Patients presenting early hallucinations or cognitive fluctuations

3. Patients with neurological disorders:

- Partial complex epilepsy

- Dementia of any origin

- Patients with Parkinson's disease

4. Any patient with a history of an intercurrent lesion found in brain imaging studies.

5. Patient presenting a major repercussion on the autonomy, assessed by Instrumental
Activities of Daily Living (IADL) Lawton score higher or equal to 2 in at least 2
items or higher than 2 in at least 1 item, confirmed by an informant person.

6. Patient having less than 14 words at the identification phase of the FCSRT (Free and
Cued Selective Reminding Test)

7. Known vitamin B12 or folates deficiency (except if replacement treatment of stable
posology since at least 6 months before selection) or known syphilis.

8. Abnormal Thyroid function (T3, T4, ultrasensitive thyroid stimulating hormone (TSH).
Euthyroid patients treated with stable doses for at least 3 months could be included.

9. Insulin dependent diabetes or diabetes not controlled by a regimen and/or oral
antidiabetics, obstructive pulmonary disease, unstable asthma, recent hematological
and/or oncological disorders (2 years).

10. Gastrointestinal, renal, hepatic, endocrine or cardiovascular clinically significant
disease. Atrioventricular block of 2nd or 3rd degree on ECG.

11. Patient with bradycardia < or = 50 beats per minute.

12. Patient with unstable hypertension (systolic blood pressure > 160 mmHg and /or
diastolic blood pressure > 95 mmHg) assessed by the investigator, the patient being
treated or not by antihypertensive drugs.

13. Patient previously treated with central cholinesterase inhibitors or memantine
whatever the duration of the treatment and the date of prescription

14. Patient treated by a non-authorized drug during the study

15. Known or suspected history (5 years) of alcoholism, or abusive drug use.

16. Patients with known hypersensitivity to donepezil chlorhydrate, to piperidine
derivatives or to one of the excipients of the drug.

17. Patients having participated in a clinical trial during the previous 3 months.

Inclusion criteria (Visit 1):

1. Patients with mild cognitive impairment (MCI) with progressive hippocampal amnestic
syndrome, isolated or associated to other cognitive disorders

2. General cognition and functional performance sufficiently preserved such that a
diagnosis of Possible or Probable Alzheimer's Disease based on clinical and
neuro-imaging findings (NINCDS-ADRDA or DSM-IV criteria) cannot be made by the site
physician at the time of the screening visit. This evidence must be fully documented
in the subject's study file.

3. Outpatient with an informant person: person from his/her close circle having a
regular weekly contact with the patient and accepting to answer to assessment
questionnaires

4. Patients having performed an electrocardiogram (ECG) within the previous 6 months

5. Visual, hearing capacities (authorized equipment) and oral or written expression,
sufficient for the correct performance of the tests (according to the physician's
opinion)

6. Clinical laboratory values must be within normal limits, or if abnormal, judged
clinically insignificant by the investigator (not likely to cause cognitive
impairment or medical instability)

7. Clinical Dementia Rating (CDR - sum of the boxes) = 0.5

Exclusion criteria (Visit 1):

1. Patients with an evolutive psychiatric pathology and/or unstable according to DSM-IV,
particularly:

- Major depressive episode ongoing or recurrent depression or bipolar disorders
according to the DSM-IV and/or score >or = 12 according to the 17-items
depressive Hamilton's Scale

- Patients presenting early hallucinations or cognitive fluctuations

2. Any patient presenting with an intercurrent lesion in MRI performed at screening must
be excluded from the study, apart from minor non-progressive lesions not altering
brain morphology

3. Patients with neurological disorders :

- Partial complex epilepsy

- Dementia of any origin

- Patients with Parkinson's disease

4. Patient with One or more MRI Exclusion criteria :

- Stroke sequelae



Age minimum: 50 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Alzheimer's Disease

Intervention(s)

Drug: Experimental 1

Drug: Placebo Comparator

Primary Outcome(s)

Evolution of the volume of the Hippocampi, measured by magnetic resonance imaging (MRI), between D0 and final visit (12 months ). [Time Frame: ( Day 0 to 12 months or in case of premature withdrawal after 6 months period]

Secondary Outcome(s)

Evolution of the neuropsychological scores between Day 0 and final visit. [Time Frame: Day 0 to 12 during treatment and at 18 months follow up]

Secondary ID(s)

E2020-E033-415

Source(s) of Monetary Support

Please refer to primary and secondary sponsors