Wernicke's aphasia caused by a stroke
Conditions
Interventions
Trade Name: Aricept 5mg
Product Name: PR1
Product Code: PR1
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Capsule, sof
Sponsors
Joint Sponsorship: University College London (UCL) & University College London Hospitals (UCLH)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 60 Patients with a Wernicke-type aphasia caused by a stroke will be recruited, that is: those with either a deficit in auditory processing of normal speech, or with a speech error pattern consistent with this syndrome (high-output, paraphasic or jargon aphasia), or both. It is likely that these patients will have sustained damage to the dominant temporal lobe or its connections as judged by CT/MRI scans. Subjects will be English native speakers; those with significant medical or psychiatric co-morbidity will be excluded, as will those with an absolute contraindication to either donepezil or MRI scanning. Patients will be in the post-acute phase (>3 month post stroke), but those with a chronic deficit may also be included as these patients can benefit from even quite late intervention. These subjects will be studied longitudinally over 7 time points, to assess the effects of the two therapeutic interventions. Patients with Wernicke-type aphasia will be recruited. That is, those with either a deficit in auditory processing of normal speech, or with a speech error pattern consistent with this syndrome (high-output, paraphasic or jargon aphasia), or both. The language deficit will have to be of a sufficient severity for the patients or their carers to complain of communication problems. Other criteria (and associated justifications): • Subjects will be English native speakers. • Subjects will be over the age of 18. • Patients will not be entered into the treatment part of the trial until three months or more has elapsed after their aphasic stroke (to allow for acute changes in cerebral auto-regulation to normalize and for early ‘spontaneous’ recovery of language function to have largely occurred. See Appendix 2 for graphs depicting rates of recovery over time). • There will be no upper limit of time since aphasic stroke (patients with a chronic deficit can benefit from even quite late intervention). • Only consent competent patients will be enrolled. 30 normal, aged-matched volunteers will also be recruited. These subjects will be right-handed, English native speakers. Those with significant medical or psychiatric co-morbidity will be excluded, as will those with an absolute contraindication to MRI scanning. Control subjects will be tested in the same manner as patients but only studied once and not exposed to either therapy. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patients: • Significant medical or psychiatric co-morbidity (unable to comply with: either the treatment regime, including the computer-based BT; or scanning (lying flat for up to 1.5 hours at a time)). • Clinical or neuroimaging evidence of significant multifocal cerebral disease (it will be difficult to interpret functional neuroimaging data). • Patients with contraindications to cholinesterase inhibitors (sick sinus syndrome, pregnancy). • Patients with contraindications to fMRI/MEG (pacemaker, non-compatible metallic implant, etc (see FIL scanning checklist for other absolute and relative contraindications)). • Severe hearing impairment (this will be checked using an audiometer). • Less than 18 years old. • Patient unable to provide informed consent (see written and pictorial information sheets for patients and their carers) Normal subjects: • Significant medical or psychiatric co-morbidity. • Contraindications to fMRI/MEG (pacemaker, non-compatible metallic implant, etc (see FIL scanning checklist for other absolute and relative contraindications)). • Severe hearing impairment. • Less than 18 years old (this population needs to be age-matched to the patient group).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Currently there is little good evidence to guide treatment of patients with post-stroke aphasia. Aphasia research has also been hampered by the lack of a good physiological measure of language function. The proposal is that, in a group of patients with post-stroke aphasia, mismatch negativity (MMN) signals produced the brain in response to specific auditory stimuli will act as a biological marker of improving auditory perception. The plan is to measure these responses over time in a group of suitable patients with a “Wernicke-type” aphasia to identify brain regions that support improving function driven by two types of therapy: Cholinergic drug therapy (using donepezil hydrochloride), and phonological training. Changes in the MMN signal will form the first main outcome measure; the second is language function and will be assessed using a battery of language tests. ; Secondary Objective: This study is designed to investigate three main hypotheses: Hypothesis 1: Main effects of stroke revealed by MEG, fMRI and psychophysical measures. Patients’ self-reported perceptual responses to parametrically modulated speech stimuli will be preferentially affected compared to their responses to parametrically modulated acoustically- matched non-speech stimuli. The neural correlates of this effect will be examined by measuring patients’ MMN responses to speech and non-speech stimuli, and by comparing this to data from normal age-matched controls. Hypothesis 2: Main effect of treatment in patients (MMN responses). The treatment effects of drug and behavioural therapy will correlate with changes in the location, emergence, amplitude or duration of the MMN responses. Hypothesis 3: Main effect of treatment in patients (behavioural responses). The treatment effects of drug and behavioural therapy will correlate with improvements in tests of la | — |
Countries
United Kingdom
Outcome results
None listed