Guanfacine for the Treatment of Spatial Neglect and Impaired Vigilance

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Trial of Guanfacine, an Alpha 2 Adrenergic Agonist, for Spatial Neglect and Impaired Vigilance Following Stroke and Focal Brain Damage

Conditions
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Stroke, Hemispatial Neglect

Intervention / Treatment
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* Drug: Guanfacine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional 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.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Guanfacine (Day 2) then Placebo (Day 4)<br>All patients received a single dose of guanfacine on Day 2 and a single dose of placebo on Day 4. | Drug: Guanfacine<br>* 2mg oral guanfacine (encapsulated)<br>* Other names: Estulic;Drug: Placebo<br>* placebo<br>|
| Experimental: Placebo (Day 2) then Guanfacine (Day 4)<br>All patients received a single dose of placebo on Day 2 and a single dose of guanfacine on Day 4. | Drug: Guanfacine<br>* 2mg oral guanfacine (encapsulated)<br>* Other names: Estulic;Drug: Placebo<br>* placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 5 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neglect, Attention, Vigilance, Stroke, Hemineglect, Unilateral Neglect, Spatial Neglect