Alzheimer's DiseasePhase 4NCT00403520
Hippocampus Study: Comparative Effect of Donepezil 10mg/d and Placebo on Clinical and Radiological Markers
A Phase 4 study testing Experimental 1 in people with Alzheimer's Disease, run by Eisai Inc. at 1 site in France.
Trial summary
The purpose of this study is to demonstrate that donepezil slows the progression of Alzheimer's disease (AD) using magnetic resonance imaging (MRI) of the brain to measure the volume of the hippocampus in patients with pre-dementia Alzheimer's disease. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- Experimental 1
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 240 participants
- Where
- 1 siteFrance
- Study dates
- Nov 2006to Aug 2010
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- Patients with mild cognitive impairment (MCI) with progressive hippocampal amnestic syndrome, isolated or associated to other cognitive disorders
- 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.
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- 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
- Patients having performed an electrocardiogram (ECG) within the previous 6 months
- Visual, hearing capacities (authorized equipment) and oral or written expression, sufficient for the correct performance of the tests (according to the physician's opinion)
- 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)
- Clinical Dementia Rating (CDR - sum of the boxes) = 0.5
Who cannot join
- 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
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- Claustrophobic patients
- Any other contra-indication to MRI
- 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
- Patients with neurological disorders:
- Partial complex epilepsy
- Dementia of any origin
- Patients with Parkinson's disease
- Any patient with a history of an intercurrent lesion found in brain imaging studies.
- 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.
- Patient having less than 14 words at the identification phase of the FCSRT (Free and Cued Selective Reminding Test)
- Known vitamin B12 or folates deficiency (except if replacement treatment of stable posology since at least 6 months before selection) or known syphilis.
- Abnormal Thyroid function (T3, T4, ultrasensitive thyroid stimulating hormone (TSH). Euthyroid patients treated with stable doses for at least 3 months could be included.
- 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).
- Gastrointestinal, renal, hepatic, endocrine or cardiovascular clinically significant disease. Atrioventricular block of 2nd or 3rd degree on ECG.
- Patient with bradycardia < or = 50 beats per minute.
- 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.
- Patient previously treated with central cholinesterase inhibitors or memantine whatever the duration of the treatment and the date of prescription
- Patient treated by a non-authorized drug during the study
- Known or suspected history (5 years) of alcoholism, or abusive drug use.
- Patients with known hypersensitivity to donepezil chlorhydrate, to piperidine derivatives or to one of the excipients of the drug.
- Patients having participated in a clinical trial during the previous 3 months.
- 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
- 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
- Patients with neurological disorders :
- Partial complex epilepsy
- Dementia of any origin
- Patients with Parkinson's disease
- Patient with One or more MRI Exclusion criteria :
- Stroke sequelae
- More than one ischemic lacuna
- Age related white matter changes on Flair images >Fazekas and Schmidt grade 2
- Active ischemic lesion on Diffusion weighted Images (DWI)
- Patient presenting a major repercussion on the autonomy, assessed by 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.
- Known vitamin B12 or folates deficiency (except if replacement treatment of stable posology since at least 6 months before selection) or known syphilis.
- Abnormal Thyroid function (T3, T4, free thyroxine index, TSH). Euthyroid patients treated with stable doses for at least 3 months could be included.
- 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).
- Gastrointestinal, renal, hepatic, endocrine or cardiovascular clinically significant disease. Atrioventricular block of 2nd or 3rd degree on ECG.
- Patients with bradycardia <= 50.
- Patients with unstable hypertension (systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 95mmHg) assessed by the investigator, the patient being treated or not by anti hypertensive drugs.
- Patient previously treated with central cholinesterase inhibitors or memantine whatever the duration of the treatment and the date of prescription
- Patient treated by a non-authorized drug during the study
- Known or suspected history (<= 5 years) of alcoholism, or abusive drug use.
- Patients with known hypersensitivity to donepezil chlorhydrate, to piperidine derivatives or to one of the excipients of the drug.
- Patients having participated in a clinical trial during the previous 3 months.
- Patient treated by a non-authorized drug during the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Assessment of the Comparative Effect of Donepezil 10mg/d and Placebo on Clinical and Radiological Markers in Patients With Mild Cognitive Disorders
The purpose of this study is to demonstrate that donepezil slows the progression of Alzheimer's disease (AD) using magnetic resonance imaging (MRI) of the brain to measure the volume of the hippocampus in patients with pre-dementia Alzheimer's disease.
Read the detailed description
The development of a new automated method of measurement of the volume of the hippocampus allows confirming these results in patients presenting with pre-dementia Alzheimer's Disease (AD), treated with donepezil in order to verify if this product is capable of stopping the speed of the atrophy of the hippocampus in patients and more specifically in those who will evolve to AD, compared to a placebo. This method is a semi automatic segmentation of the hippocampus from MRI, made by competitive region growing.
It was developed at the cognitive neurosciences and MRI laboratory in Pitié-Salpêtrière hospital. This method was validated on healthy subjects and Alzheimer's disease patients by comparison with manual segmentation.
Neuropsychological tests will be realized in order to supervise the clinical evolution of the patients and to correlate these results to the progression of the atrophy of the hippocampus.
- Conditions
- Alzheimer's Disease
- Being tested
- Experimental 1, Placebo Comparator
- Keywords
- Alzheimer's disease, Mild cognitive impairment
- Medical subject headings
- Alzheimer Disease, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Experimental 1Drug
Drug: Donepezil Hydrochloride 10 mg orally for 12 months
Placebo ComparatorDrug
Drug: Placebo Matching placebo orally for 12 months
| Study group | Role | What they receive |
|---|---|---|
| Experimental 1 | Experimental | Not described Receives: Drug: Experimental 1 |
| Placebo Comparator | Placebo comparator | Not described Receives: Drug: Placebo Comparator |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evolution of the volume of the Hippocampi, measured by magnetic resonance imaging (MRI), between D0 and final visit (12 months ).
Measured: ( Day 0 to 12 months or in case of premature withdrawal after 6 months period
Secondary outcomes (1)
Evolution of the neuropsychological scores between Day 0 and final visit.
Outcome Measure Description: Patients will perform neuropsychological and independence tests including (16 items free recall/cued recall test using the Grober-Buschke method, Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR) sum of the boxes and Instrumental Activities of Daily Living (IADL), and will be evaluated using the Hamilton Scale.
Measured: Day 0 to 12 during treatment and at 18 months follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2006 (estimated)
- Study startNov 2006
- Primary completionMar 2008
- Study completionAug 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- More trials run by Eisai Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 240 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Isabelle Tonelli, Study director, Eisai France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00403520
- Sponsor's protocol ID
- E2020-E033-415
- Status last verified
- Jul 2014
- First submitted
- 21 Nov 2006
- Last updated
- 14 Jul 2014
- Results posted
- No
Publications
Diaz-Galvan P, Lorenzon G, Mohanty R, Martensson G, Cavedo E, Lista S, Vergallo A, Kantarci K, Hampel H, Dubois B, Grothe MJ, Ferreira D, Westman E. Differential response to donepezil in MRI subtypes of mild cognitive impairment. Alzheimers Res Ther. 2023 Jun 23;15(1):117. doi: 10.1186/s13195-023-01253-2.
PubMed 37353809Cavedo E, Dubois B, Colliot O, Lista S, Croisile B, Tisserand GL, Touchon J, Bonafe A, Ousset PJ, Rouaud O, Ricolfi F, Vighetto A, Pasquier F, Galluzzi S, Delmaire C, Ceccaldi M, Girard N, Lehericy S, Duveau F, Chupin M, Sarazin M, Dormont D, Hampel H; Hippocampus Study Group. Reduced Regional Cortical Thickness Rate of Change in Donepezil-Treated Subjects With Suspected Prodromal Alzheimer's Disease. J Clin Psychiatry. 2016 Dec;77(12):e1631-e1638. doi: 10.4088/JCP.15m10413.
PubMed 27780331Teipel SJ, Cavedo E, Grothe MJ, Lista S, Galluzzi S, Colliot O, Chupin M, Bakardjian H, Dormont D, Dubois B, Hampel H; Hippocampus Study Group. Predictors of cognitive decline and treatment response in a clinical trial on suspected prodromal Alzheimer's disease. Neuropharmacology. 2016 Sep;108:128-35. doi: 10.1016/j.neuropharm.2016.02.005. Epub 2016 Feb 10.
PubMed 26876309
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of the Comparative Effect of Donepezil 10mg/d and Placebo on Clinical and Radiological Markers in Patients With Mild Cognitive Disorders
- ClinicalTrials.gov ID
- NCT00403520
- Acronym / sponsor ID
- E2020-E033-415
- Conditions
- Alzheimer's Disease
- Keywords
- Alzheimer's disease, Mild cognitive impairment
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 240 participants (actual)
- Lead sponsor
- Eisai Inc.Industry (pharma, biotech, devices)
- Study start
- Nov 2006
- Primary completion
- Mar 2008 (actual)
- Study completion
- Aug 2010 (actual)
- First posted
- 23 Nov 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to demonstrate that donepezil slows the progression of Alzheimer's disease (AD) using magnetic resonance imaging (MRI) of the brain to measure the volume of the hippocampus in patients with pre-dementia Alzheimer's disease.
Detailed description
The development of a new automated method of measurement of the volume of the hippocampus allows confirming these results in patients presenting with pre-dementia Alzheimer's Disease (AD), treated with donepezil in order to verify if this product is capable of stopping the speed of the atrophy of the hippocampus in patients and more specifically in those who will evolve to AD, compared to a placebo. This method is a semi automatic segmentation of the hippocampus from MRI, made by competitive region growing.
It was developed at the cognitive neurosciences and MRI laboratory in Pitié-Salpêtrière hospital. This method was validated on healthy subjects and Alzheimer's disease patients by comparison with manual segmentation.
Neuropsychological tests will be realized in order to supervise the clinical evolution of the patients and to correlate these results to the progression of the atrophy of the hippocampus.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental 1 | Experimental | Drug: Experimental 1 |
| Placebo Comparator | Placebo comparator | Drug: Placebo Comparator |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
- Patients with mild cognitive impairment (MCI) with progressive hippocampal amnestic syndrome, isolated or associated to other cognitive disorders
Key exclusion criteria (55 listed)
- Patients with a contraindication to MRI:
- Patients with an evolutive psychiatric pathology and/or unstable according to DSM-IV, particularly:
- Patients with neurological disorders:
- Any patient with a history of an intercurrent lesion found in brain imaging studies.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Experimental 1Drug: Donepezil Hydrochloride 10 mg orally for 12 months | Drug | Experimental 1 |
| Placebo ComparatorDrug: Placebo Matching placebo orally for 12 months | Drug | Placebo Comparator |
Primary outcome
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
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2014.
- Derived from this study: PubMed 37353809Diaz-Galvan P, Lorenzon G, Mohanty R, Martensson G, Cavedo E, Lista S, Vergallo A, Kantarci K, Hampel H, Dubois B, Grothe MJ, Ferreira D, Westman E. Differential response to donepezil in MRI subtypes of mild cognitive impairment. Alzheimers Res Ther. 2023 Jun 23;15(1):117. doi: 10.1186/s13195-023-01253-2.
- Derived from this study: PubMed 27780331Cavedo E, Dubois B, Colliot O, Lista S, Croisile B, Tisserand GL, Touchon J, Bonafe A, Ousset PJ, Rouaud O, Ricolfi F, Vighetto A, Pasquier F, Galluzzi S, Delmaire C, Ceccaldi M, Girard N, Lehericy S, Duveau F, Chupin M, Sarazin M, Dormont D, Hampel H; Hippocampus Study Group. Reduced Regional Cortical Thickness Rate of Change in Donepezil-Treated Subjects With Suspected Prodromal Alzheimer's Disease. J Clin Psychiatry. 2016 Dec;77(12):e1631-e1638. doi: 10.4088/JCP.15m10413.
- Derived from this study: PubMed 26876309Teipel SJ, Cavedo E, Grothe MJ, Lista S, Galluzzi S, Colliot O, Chupin M, Bakardjian H, Dormont D, Dubois B, Hampel H; Hippocampus Study Group. Predictors of cognitive decline and treatment response in a clinical trial on suspected prodromal Alzheimer's disease. Neuropharmacology. 2016 Sep;108:128-35. doi: 10.1016/j.neuropharm.2016.02.005. Epub 2016 Feb 10.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Isabelle Tonelli study director
Eisai France
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Experimental 1 in people with Alzheimer's Disease, run by Eisai Inc. at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 55 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00403520, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2014.