Guanfacine for the Treatment of Spatial Neglect and Impaired Vigilance

Phase 2

Completed

• Conditions: Stroke; Hemispatial Neglect
• Interventions: Drug: Guanfacine; Drug: Placebo

• Registration Number: NCT00955253
• Lead Sponsor: Imperial College London

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.

Study Timeline

• Study First Submitted: 2009-08-07
• Study First Submitted QC: 2009-08-07
• Study First Posted: 2009-08-10
• Study Start: 2010-04
• Primary Completion: 2014-03-28
• Study Completion: 2014-03-28
• Results First Submitted: 2019-02-22
• Results First Submitted QC: 2019-06-10
• Results First Posted: 2019-08-02
• Status Verified: 2020-01
• Last Update Submitted: 2020-01-06
• Last Update Posted: 2020-01-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

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.

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Guanfacine (Day 2) then Placebo (Day 4)	Guanfacine	All patients received a single dose of guanfacine on Day 2 and a single dose of placebo on Day 4.
Guanfacine (Day 2) then Placebo (Day 4)	Placebo	All patients received a single dose of guanfacine on Day 2 and a single dose of placebo on Day 4.
Placebo (Day 2) then Guanfacine (Day 4)	Placebo	All patients received a single dose of placebo on Day 2 and a single dose of guanfacine on Day 4.
Placebo (Day 2) then Guanfacine (Day 4)	Guanfacine	All patients received a single dose of placebo on Day 2 and a single dose of guanfacine on Day 4.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

Imperial College Healthcare NHS Trust; 🇬🇧 London, United Kingdom