Clinical trial NCT00955253: Guanfacine for the Treatment of Spatial Neglect and Impaired Vigilance
Official title: A Trial of Guanfacine, an Alpha 2 Adrenergic Agonist, for Spatial Neglect and Impaired Vigilance Following Stroke and Focal Brain Damage
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Stroke
Hemispatial Neglect
Keywords: Neglect
Attention
Vigilance
Stroke
Hemineglect
Unilateral Neglect
Spatial Neglect
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: Wellcome Trust
First posted: 2009-08-10
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Performance on Tests of Hemispatial Neglect and Sustained Attention
timeFrame: 5 days
Secondary outcomes:
measure: Performance on Motor Tasks
timeFrame: 5 Days
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
Study officials:
affiliation: Imperial College London
name: Paresh A Malhotra, PhD MRCP
role: PRINCIPAL_INVESTIGATOR
affiliation: University College, London
name: Masud Husain, DPhil FRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: Malhotra PA, Parton AD, Greenwood R, Husain M. Noradrenergic modulation of space exploration in visual neglect. Ann Neurol. 2006 Jan;59(1):186-90. doi: 10.1002/ana.20701.
citation: Dalmaijer ES, Li KMS, Gorgoraptis N, Leff AP, Cohen DL, Parton AD, Husain M, Malhotra PA. Randomised, double-blind, placebo-controlled crossover study of single-dose guanfacine in unilateral neglect following stroke. J Neurol Neurosurg Psychiatry. 2018 Jun;89(6):593-598. doi: 10.1136/jnnp-2017-317338. Epub 2018 Feb 7.