Guanfacine for the Treatment of Spatial Neglect and Impaired Vigilance (GASNIV)

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 Overview

• Status: Completed
• Conditions: Stroke; Hemispatial Neglect
• Intervention / Treatment: Drug: Placebo; Drug: Guanfacine

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 Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W6 8RF
    • Imperial College Healthcare NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: Wellcome Trust
• Investigators: Principal Investigator: Paresh A Malhotra, PhD MRCP, Imperial College London; Principal Investigator: Masud Husain, DPhil FRCP, University College, London

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2010
• Primary Completion (Actual): March 28, 2014
• Study Completion (Actual): March 28, 2014

Study Registration Dates

• First Submitted: August 7, 2009
• First Submitted That Met QC Criteria: August 7, 2009
• First Posted (Estimate): August 10, 2009

Study Record Updates

• Last Update Posted (Actual): January 21, 2020
• Last Update Submitted That Met QC Criteria: January 6, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Stroke; Attention; Spatial Neglect; Vigilance; Neglect; Hemineglect; Unilateral Neglect
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Stroke; Perceptual Disorders; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Guanfacine
• Other Study ID Numbers: CRO1234; NRES09/H0711/5 (Other Identifier: National Research Ethics Service); 2008-001160-36 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No