Hemispatial Neglect, Stroke
Conditions
Keywords
Neglect, Attention, Vigilance, Stroke, Hemineglect, Unilateral Neglect, Spatial Neglect
Brief summary
To find out if spatial neglect following stroke and brain injury can be reduced using guanfacine, a drug that was shown to improve neglect in two stroke patients in a previous pilot study (Malhotra et al, 2006). In this trial, the effects of guanfacine will be examined in a larger number of patients, and there will also be a systematic assessment of whether the drug is only effective in patients with particular patterns of brain damage.
Detailed description
The current study has a double-blind crossover design where patients will receive a single 2mg dose of oral guanfacine and a single dose of placebo. They will receive one of these on Day 2 of the study period and the other on Day 4. They will be tested daily on Days 1 to 5 so that any test repetition or long-term drug effects can be gauged. On days 2 and 4 they will be tested twice-once prior to drug/placebo administration and again 90 minutes after drug/placebo administration. Tests will include standard pen-and-paper tasks for neglect as well as computerised tests of sustained attention and visual exploration. In our published pilot study (Malhotra et al, 2006) there was a suggestion that patients without damage to frontal cortex were more likely to respond to guanfacine. In the current study we intend to test 10 patients with and 10 patients without frontal damage in order to test this further.
Interventions
DRUGGuanfacine
2mg oral guanfacine (encapsulated)
DRUGPlacebo
placebo
Sponsors
Wellcome Trust
Imperial College London
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
The order of administration of guanfacine and placebo was counterbalanced across patients, according to a pregenerated randomisation scheme. The clinician who administered the drugs and the tests was blind to the randomisation and the drug.
Intervention model description
Patients were tested on five consecutive days. On days 1, 3 and 5, they were tested on a task battery. On day 2, individuals received active drug or placebo, and on day 4 they received placebo if they had previously received active drug and vice versa. The order of administration of guanfacine and placebo was counterbalanced across patients, according to a pregenerated randomisation scheme. The clinician who administered the drugs and the tests was blind to the randomisation and the drug. The analyses presented here were performed by a different researcher, only after all data were collected. On both treatment days, patients were tested on the task battery twice: once immediately before guanfacine/placebo administration and once 2 hours after.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 or more * Greater than 2 weeks following stroke * Ability to give consent * Evidence of robust Visual Neglect when tested twice with cancellation tasks.
Exclusion criteria
* Less than 2 weeks following stroke * Concomitant illness that may affect interpretation of any findings * Labile blood pressure following stroke * Systolic BP less than 100 mmHg and / or diastolic less than 70 mmHg * New antihypertensive medication started within last 3 weeks * Patients with hepatic or renal dysfunction * Patients receiving other medications known to potentiate guanfacine's antihypertensive and hypotensive effects or cause torsade de pointes, specifically antipsychotics (including sultopride, chlorpromazine, thioridazine, amisulpiride, sulpiride, haloperidol), and moxifloxacin, baclofen, verapamil, quinidine, hydroquinidine, dispyramide, amiodarone, dofetilide, ibutilide, sotalol, pimozide, bepridil, cisapride, diphemanil, erythromycin IV, halofantrine, pentamidine, sparfloxacin, vincamine, alfuzosin, prazosin, terazosin, tamsulosin, amifostine * Patients with diagnosis of brain tumour * Patients with weight less than 55kg * Patients who are pregnant * Mothers who are breast feeding * Patients with severe coronary insufficiency or myocardial infarction in previous 6 months * Cognitive impairment, dysphasia or dementia that prevents patient from giving informed consent * Severe mental impairment or physical handicap following stroke that prevents patients from giving consent or performing basic (standard clinical) tests for neglect
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Performance on Tests of Hemispatial Neglect and Sustained Attention | 5 days | Touchscreen Cancellation: This is a computerised scale for measuring the severity of spatial neglect as described in previous publications (Malhotra et al, Annals of Neurology 2006; Parton et al, Neuroreport 2006). Patients are asked to find and touch targets (which are embedded amongst distractors) on a touchscreen. In the variant of the task employed here, the targets are not marked when touched (Invisible Cancellation).The maximum number of targets that can be found is 64 (Therefore minimum score =0, maximum = 64), which represents normal performance. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Performance on Motor Tasks | 5 Days | Time taken to take pegs from a container and place them into holes on a board, and then remove these pegs and replace them in the container. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Drug and Placebo All patients will receive a single dose of drug and a single dose of placebo on separate days of the trial period. The order in which they receive these will be randomized.
Guanfacine: 2mg oral guanfacine (encapsulated)
Placebo: placebo | 13 |
| Total | 13 |
Baseline characteristics
| Characteristic | Drug and Placebo |
|---|---|
| Age, Continuous | 63.2 years STANDARD_DEVIATION 10.3 |
| Behavioural Inattention Test Star Cancellation Score (Total targets found) | 35.4 Number of targets found STANDARD_DEVIATION 15.9 |
| Mesulam Shape Cancellation Score (Total targets found) | 25.6 Number of targets found STANDARD_DEVIATION 13.7 |
| Region of Enrollment United Kingdom | 13 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 12 Participants |
| Touchscreen Cancellation | 28.4 Number of targets found STANDARD_DEVIATION 13.9 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 13 |
| other Total, other adverse events | 0 / 13 |
| serious Total, serious adverse events | 0 / 13 |
Outcome results
Primary
Performance on Tests of Hemispatial Neglect and Sustained Attention
Touchscreen Cancellation: This is a computerised scale for measuring the severity of spatial neglect as described in previous publications (Malhotra et al, Annals of Neurology 2006; Parton et al, Neuroreport 2006). Patients are asked to find and touch targets (which are embedded amongst distractors) on a touchscreen. In the variant of the task employed here, the targets are not marked when touched (Invisible Cancellation).The maximum number of targets that can be found is 64 (Therefore minimum score =0, maximum = 64), which represents normal performance.
Time frame: 5 days
Population: Baseline performance was determined for each patient by averaging scores on days 1, 3 and 5, as well as the preadministration sessions on days 2 and 4. Group averages and differences were computed between treatment type (baseline, guanfacine and placebo) across individuals.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Patients | Performance on Tests of Hemispatial Neglect and Sustained Attention | Touchscreen Cancellation-Guanfacine | 31.15 Number of targets found | Standard Deviation 15.1 |
| All Patients | Performance on Tests of Hemispatial Neglect and Sustained Attention | Touchscreen Cancellation-Placebo | 26.15 Number of targets found | Standard Deviation 14.29 |
Comparison: between the placebo and guanfacine conditionsp-value: 0.013t-test, 2 sided
Secondary
Performance on Motor Tasks
Time taken to take pegs from a container and place them into holes on a board, and then remove these pegs and replace them in the container.
Time frame: 5 Days
Population: All patients were unable to carry out this task (9 hold PEG test of finger dexterity) because of the paralysis caused by their stroke.