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| ID | Type | Description | Link |
|---|---|---|---|
| NRES09/H0711/5 | Other Identifier | National Research Ethics Service | |
| 2008-001160-36 | EudraCT Number |
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| Name | Class |
|---|---|
| Wellcome Trust | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Guanfacine | Drug | 2mg oral guanfacine (encapsulated) |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Paresh A Malhotra, PhD MRCP | Imperial College London | Principal Investigator |
| Masud Husain, DPhil FRCP | University College, London | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Imperial College Healthcare NHS Trust | London | W6 8RF | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16261567 | Background | 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. | |
| 29436486 | Result | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Guanfacine Then Placebo | This group individuals are randomised to receive Guanfacine at the first treatment session and Placebo at the second treatment session. |
| FG001 | Placebo Then Guanfacine | This group individuals are randomised to receive Placebo at the first treatment session and Guanfacine at the second treatment session. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention (Day 2) |
| |||||||||||||
| Second Intervention (Day 4) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Drug and Placebo | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | 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. | Posted | Mean | Standard Deviation | Number of targets found | 5 days |
|
5 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | All Patients | All individuals received guanfacine and placebo in a crossover design. |
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The trial involved a single dose of active drug and a single dose of placebo given in a crossover design.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Paresh Malhotra | Imperial College London | 0208 846 1234 | p.malhotra@imperial.ac.uk |
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| ID | Term |
|---|---|
| D020521 | Stroke |
| D010468 | Perceptual Disorders |
| ID | Term |
|---|---|
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D016316 | Guanfacine |
| ID | Term |
|---|---|
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
| D010648 | Phenylacetates |
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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.
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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.
| Placebo | Drug | placebo |
|
| NOT COMPLETED |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Behavioural Inattention Test Star Cancellation Score (Total targets found) | This is a standard scale for measuring the severity of spatial neglect. Patients are asked to find and mark targets (which are embedded amongst distractors) on a piece of paper. The maximum number of targets that can be found is 54 (Therefore minimum score =0, maximum =54), which represents normal performance. | Mean | Standard Deviation | Number of targets found |
|
| Mesulam Shape Cancellation Score (Total targets found) | This is a standard scale for measuring the severity of spatial neglect. Patients are asked to find and mark targets (which are embedded amongst distractors) on a piece of paper. The maximum number of targets that can be found is 60 (Therefore minimum score =0, maximum = 60), which represents normal performance. | Mean | Standard Deviation | Number of targets found |
|
| 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. | Mean | Standard Deviation | Number of targets found |
|
All individuals received guanfacine and placebo in a crossover design. |
|
|
|
| Secondary | 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. | All patients were unable to carry out this task (9 hold PEG test of finger dexterity) because of the paralysis caused by their stroke. | Posted | 5 Days |
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| 0 |
| 13 |
| 0 |
| 13 |
| 0 |
| 13 |
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| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000146 |
| Acids, Carbocyclic |
| D002264 | Carboxylic Acids |