Guanfacine for the Treatment of Spatial Neglect and Impaired Vigilance

NCT00955253 | Completed Phase 2 Results DMC

• 3 other identifiers: CRO1234NRES09/H0711/52008-001160-36
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Stroke; Hemispatial Neglect

Keywords

Neglect; Attention; Vigilance; Stroke; Hemineglect; Unilateral Neglect; Spatial Neglect

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Performance on Motor Tasks

  5 Days

Study Arms (2)

Guanfacine (Day 2) then Placebo (Day 4)

EXPERIMENTAL

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

Drug: Guanfacine; Drug: Placebo

Placebo (Day 2) then Guanfacine (Day 4)

EXPERIMENTAL

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

Drug: Guanfacine; Drug: Placebo

Interventions

Guanfacine DRUG

2mg oral guanfacine (encapsulated)

Also known as: Estulic

Guanfacine (Day 2) then Placebo (Day 4); Placebo (Day 2) then Guanfacine (Day 4)

Placebo DRUG

placebo

Guanfacine (Day 2) then Placebo (Day 4); Placebo (Day 2) then Guanfacine (Day 4)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Imperial College London: lead
• Wellcome Trust: collaborator

Study Sites (1)

Imperial College Healthcare NHS Trust

London, W6 8RF, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 16261567 BACKGROUND

• 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.

  PMID: 29436486 RESULT

MeSH Terms

Conditions

Stroke; Perceptual Disorders

Interventions

Guanfacine

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids

Limitations and Caveats

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

Results Point of Contact

• Title: Dr Paresh Malhotra
• Organization: Imperial College London

p.malhotra@imperial.ac.uk

0208 846 1234

Study Officials

• Paresh A Malhotra, PhD MRCP

  Imperial College London

  PRINCIPAL INVESTIGATOR

• Masud Husain, DPhil FRCP

  University College, London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 7, 2009
• First Posted: August 10, 2009
• Study Start: April 1, 2010
• Primary Completion: March 28, 2014
• Study Completion: March 28, 2014
• Last Updated: January 21, 2020
• Results First Posted: August 2, 2019

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)