E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Amnestic Mild cognitive Impairment (aMCI) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10009846 |
E.1.2 | Term | Cognitive impairment |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objective of this study is to define the short term effects of the existing Alzheimer's Disease(AD) symptomatic treatment compound donepezil on cognitive EEG/ERP and fMRI endpoints in normal elderly and amnestic mild cognitive impairment (aMCI) cohorts.The overall goal of the study is to develop EEG/ERP and fMRI measures that can detect pharmacodynamic effects in subjects with aMCI and elderly controls after one dose of the medication that has been approved for symptomatic treatment in AD.These measures can then be used for the future assessment of potential novel treatments for AD. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Older controls: 1.Aged 55-85 years 2.Absence of symptoms of cognitive impairment 3.MMSE score of 27 or higher 4.Test scores on the neuropsychological battery (see below) that are not more than 1 SD below age-adjusted norms 5.If history of alcohol dependence: abstinent for 10 years prior to study 6.If on antidepressants: mood stable on same dose for 3 months prior to study(bellow cutoff scores on the Hospital Anxiety and Depression Scale) 7.Be MRI compatible as per St James’s Hospital Centre for Advanced Imaging (CAMI)MRI screening form
aMCI 1.Aged 55-85 years 2.symptoms of cognitive impairment of at least 6 months 3.the diagnosis of "not demented" (i.e. CDR status of 0 or 0.5) 4.must score greater than 1.5 SD below aged norms on at least one of the following:WMS-111 -logical memory,visual reproduction or face recognition 5.only include as aMCI delayed measures and not immediate measures 6.meet consensus criteria for amnestic MCI (aMCI; Winblad et al,2004) 7.If history of alcohol dependence: abstinent for 10 years prior to onset of memory loss and memory loss not related tot alcohol as judged by investigator. 8.If on antidepressants: mood stable on same dose for 3 months prior to study(below cutoff scores on the Hospital Anxiety and Depression Scale) 9.Be MRI compatible as per St James’s Hospital Centre for Advanced Imaging (CAMI)MRI screening form |
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E.4 | Principal exclusion criteria |
1.Active medical disease or untreated psychiatric disease 2.History of stroke,epilepsy/seizure disorder,heart attack,syncopal,episodes of unexplained loss of consciousness 3.History of head injury where:Post-traumatic amnesia greater than 24 hours, CT evidence of brain injury, clinically significant post-traumatic sequealae as judged by investigator or loss of consciousness for more than 1 hour 4.History of major psychiatric illness excluding controlled depression 5.Currently taking psychotropic medication, benzodiazepines or oral steroids 6.History or presence of drug abuse 7.Current alcohol dependence/abuse 8.Scoring above cut-offs on screening anxiety and depression scales (the Hospital Anxiety and Depression Scale (HADS) depression score >8, anxiety score >8) . 9.If English is not their first language. 10.Any contraindications to taking donepezil as specified in the Summary of Product Characteristics, including history or presence of asthma and seizures. 11.Clinically significant abnormalities on screening ECG, including but not limited to conduction abnormalities or heart rate <55 beats / min as judged by the investigator 12.Clinically significant abnormalities on screening laboratory tests as judged by the investigator 13. Clinically significant chronic obstructive airways disease and peptic ulcer disease as judged by investigator
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E.5 End points |
E.5.1 | Primary end point(s) |
Changes in P3a ERP amplitude and latency Changes in P3b ERP amplitude and latency Changes in frequency and power Changes in alpha blocking/desynchronisation Increases in slow wave power (delta and theta) related to downward shifts in arousal or increases in theta/beta ratio
The EEG will guide the fMRI analysis. With the incorporation of fMRI the precise anatomical regions where the drugs are impacting on neural activity can be elucidated.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of last subject undergoing the trial |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |