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

Primary Purpose

Stroke, Hemispatial Neglect

Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Guanfacine
Placebo
Sponsored by
Imperial College London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stroke focused on measuring Neglect, Attention, Vigilance, Stroke, Hemineglect, Unilateral Neglect, Spatial Neglect

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Imperial College Healthcare NHS Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Guanfacine (Day 2) then Placebo (Day 4)

Placebo (Day 2) then Guanfacine (Day 4)

Arm Description

All patients received a single dose of guanfacine on Day 2 and a single dose of placebo on Day 4.

All patients received a single dose of placebo on Day 2 and a single dose of guanfacine on Day 4.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
August 7, 2009
Last Updated
January 6, 2020
Sponsor
Imperial College London
Collaborators
Wellcome Trust
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1. Study Identification

Unique Protocol Identification Number
NCT00955253
Brief Title
Guanfacine for the Treatment of Spatial Neglect and Impaired Vigilance
Acronym
GASNIV
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

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
April 2010 (Actual)
Primary Completion Date
March 28, 2014 (Actual)
Study Completion Date
March 28, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Imperial College London
Collaborators
Wellcome Trust

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stroke, Hemispatial Neglect
Keywords
Neglect, Attention, Vigilance, Stroke, Hemineglect, Unilateral Neglect, Spatial Neglect

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
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.
Masking
ParticipantCare ProviderInvestigator
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.
Allocation
Randomized
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Guanfacine (Day 2) then Placebo (Day 4)
Arm Type
Experimental
Arm Description
All patients received a single dose of guanfacine on Day 2 and a single dose of placebo on Day 4.
Arm Title
Placebo (Day 2) then Guanfacine (Day 4)
Arm Type
Experimental
Arm Description
All patients received a single dose of placebo on Day 2 and a single dose of guanfacine on Day 4.
Intervention Type
Drug
Intervention Name(s)
Guanfacine
Other Intervention Name(s)
Estulic
Intervention Description
2mg oral guanfacine (encapsulated)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
placebo
Primary Outcome Measure Information:
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
Secondary Outcome Measure Information:
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paresh A Malhotra, PhD MRCP
Organizational Affiliation
Imperial College London
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Masud Husain, DPhil FRCP
Organizational Affiliation
University College, London
Official's Role
Principal Investigator
Facility Information:
Facility Name
Imperial College Healthcare NHS Trust
City
London
ZIP/Postal Code
W6 8RF
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
16261567
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.
Results Reference
background
PubMed Identifier
29436486
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.
Results Reference
result

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Guanfacine for the Treatment of Spatial Neglect and Impaired Vigilance

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