GASNIV: Guanfacine for the Treatment of Spatial Neglect and Impaired Vigilance

• Sponsor: Imperial College London (Other)
• Overall Status: Completed
• CT.gov ID: NCT00955253
• Collaborator: Wellcome Trust (Other)
• Enrollment: 13
• Location: 1
• Arms: 2
• Actual Duration (Months): 47.9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Stroke; Hemispatial Neglect	Drug: Guanfacine; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• 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.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 (Participant, Care Provider, Investigator)
• Masking Description: 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.
• Primary Purpose: Treatment
• Official Title: A Trial of Guanfacine, an Alpha 2 Adrenergic Agonist, for Spatial Neglect and Impaired Vigilance Following Stroke and Focal Brain Damage
• Actual Study Start Date: Apr 1, 2010
• Actual Primary Completion Date: Mar 28, 2014
• Actual Study Completion Date: Mar 28, 2014

Arms and Interventions

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: Guanfacine; 2mg oral guanfacine (encapsulated); Other Names: Estulic ; Drug: Placebo; placebo
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: Guanfacine; 2mg oral guanfacine (encapsulated); Other Names: Estulic ; Drug: Placebo; placebo

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Imperial College Healthcare NHS Trust	London		United Kingdom	W6 8RF

Sponsors and Collaborators

• Imperial College London
• Wellcome Trust

Investigators

• Principal Investigator: Paresh A Malhotra, PhD MRCP, Imperial College London
• Principal Investigator: Masud Husain, DPhil FRCP, University College, London

Study Documents (Full-Text)

None provided.

More Information

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.

• Responsible Party: Imperial College London
• ClinicalTrials.gov Identifier: NCT00955253
• Other Study ID Numbers: CRO1234; NRES09/H0711/5; 2008-001160-36
• First Posted: Aug 10, 2009
• Last Update Posted: Jan 21, 2020
• Last Verified: Jan 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Imperial College London: Neglect; Attention; Vigilance; Stroke; Hemineglect; Unilateral Neglect; Spatial Neglect
• Additional relevant MeSH terms: Stroke; Perceptual Disorders; Guanfacine

Study Results

Participant Flow

Arm/Group Title	Guanfacine Then Placebo	Placebo Then Guanfacine
Arm/Group Description	This group individuals are randomised to receive Guanfacine at the first treatment session and Placebo at the second treatment session.	This group individuals are randomised to receive Placebo at the first treatment session and Guanfacine at the second treatment session.
Period Title: First Intervention (Day 2)
STARTED	7	6
COMPLETED	7	6
NOT COMPLETED	0	0
Period Title: First Intervention (Day 2)
STARTED	7	6
COMPLETED	7	6
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Drug and Placebo
Arm/Group Description	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. Guanfacine: 2mg oral guanfacine (encapsulated) Placebo: placebo
Overall Participants	13
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.2 (10.3)
Sex: Female, Male (Count of Participants)
Female	1 7.7%
Male	12 92.3%
Region of Enrollment (Count of Participants)
United Kingdom	13 100%
Behavioural Inattention Test Star Cancellation Score (Total targets found) (Number of targets found) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Number of targets found]	35.4 (15.9)
Mesulam Shape Cancellation Score (Total targets found) (Number of targets found) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Number of targets found]	25.6 (13.7)
Touchscreen Cancellation (Number of targets found) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Number of targets found]	28.4 (13.9)

Outcome Measures

1. Primary Outcome

Title	Performance on Tests of Hemispatial Neglect and Sustained Attention
Description	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.
Time Frame	5 days

Outcome Measure Data

Analysis Population Description

Baseline performance was determined for each patient by averaging scores on days 1, 3 and 5, as well as the preadministration sessions on days 2 and 4. Group averages and differences were computed between treatment type (baseline, guanfacine and placebo) across individuals.

Arm/Group Title	All Patients
Arm/Group Description	All individuals received guanfacine and placebo in a crossover design.
Measure Participants	13
Touchscreen Cancellation-Guanfacine	31.15 (15.1)
Touchscreen Cancellation-Placebo	26.15 (14.29)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Patients
	Comments	between the placebo and guanfacine conditions
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.013
	Comments
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Performance on Motor Tasks
Description	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.
Time Frame	5 Days

Outcome Measure Data

Analysis Population Description

All patients were unable to carry out this task (9 hold PEG test of finger dexterity) because of the paralysis caused by their stroke.

Arm/Group Title	All Patients
Arm/Group Description	All patients received guanfacine then placebo or vice versa.
Measure Participants	0

Adverse Events

Time Frame	5 days
Arm/Group Title	All Patients
Arm/Group Description	All individuals received guanfacine and placebo in a crossover design.
All Cause Mortality
	All Patients
	Affected / at Risk (%)	# Events
Total	0/13 (0%)
Serious Adverse Events
	All Patients
	Affected / at Risk (%)	# Events
Total	0/13 (0%)
Other (Not Including Serious) Adverse Events
	All Patients
	Affected / at Risk (%)	# Events
Total	0/13 (0%)

Limitations/Caveats

The trial involved a single dose of active drug and a single dose of placebo given in a crossover design.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.