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

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Crossover Assignment, Efficacy Study

Study Primary Completion Date: April 2011

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.

Intervention(s) in this Clinical Trial

• Drug: Guanfacine
  • 2mg oral guanfacine (encapsulated)
• Drug: Placebo
  • placebo

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 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.

Primary Measures

• Performance on tests of hemispatial neglect and sustained attention
  • Time Frame: 5 days
    Safety Issue?: No

Secondary Measures

• Performance on Motor Tasks
  • Time Frame: 5 Days
    Safety Issue?: 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Imperial College London

Overall Clinical Trial Officials and Contacts

Paresh A Malhotra, PhD MRCP Principal Investigator Imperial College London  

Information obtained from ClinicalTrials.gov on February 08, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00955253

Study ID Number: CRO1234

ClinicalTrials.gov Identifier: NCT00955253

Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency