Cerebrovascular DisordersPhase 3NEGLECTNCT01000103
Using Repetitive Transcranial Magnetic Stimulation (rTMS) in the Rehabilitation of Chronic Spatial Neglect After Stroke
A Phase 3 study testing Real rTMS in people with Cerebrovascular Disorders and Cerebral Stroke, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Visuospatial neglect is a common neurological symptom which appears following strokes on regions of the right hemisphere of the brain. It affects patient's self representation and awareness of the space, impairing functional rehabilitation and adaptation back to a normal life. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Cerebrovascular Disorders, Cerebral Stroke, VISIO-spatial Neglect
- What is being tested?
- Real rTMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 34 participants
- Where
- 1 siteFrance
- Study dates
- 24 Mar 2010to 15 Oct 2014
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Unilateral right hemisphere stroke
- Visuospatial neglect or extinction at the time of entry, as determined by at least 1 test of the battery (BEN) displaying pathological scores (cut off values as defined in AZOUVI et al. JNNP 2004, Table 1), or an ECB test, score > 8
- A period of evolution of at least 3 months since stroke event
- Age between 18 and 75 years old
- Affiliation to Social Security system
- Informed consent signature
Who cannot join
- Criteria related to the stroke:
- Bilateral stroke lesions: left hemispheric focal lesion excluding leucoaraiosis or mild lesions of the white matter
- Criteria related to rTMS:
- Metal in the head, or a history of prior neurosurgical procedures
- Ferromagnetic bioimplants activated by any electronic, mechanical or magnetic means such as: cochlear implants, pacemakers, medication pumps, vagal stimulators, deep brain stimulators, neurostimulators, bio stimulators, or ventriculoperitoneal shunts.
- Prior history of seizures or seizure events following the stroke requiring the use of antiepileptic drugs
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- Pregnancy (by history or positive urine pregnancy test)
- A urine pregnancy test will be done on all women of childbearing potential (those who have started menstruating up until they have stopped menstruating) prior to each MRI session, to rule out pregnancy.
- Diagnosis of tinnitus
- Participation in any experimental neglect rehabilitation project for at least 5 weeks before and 2 weeks after the stimulation, or during the 6 months of follow-up.
- Prior participation in TMS based treatments or experiments
- Criteria related to feasibility:
- Incapacity to follow and complete the stimulation and follow-up protocol
- Other medical cerebral conditions other than the condition studied in the present protocol
- Any general medical condition, which could potentially interfere with clinical progression
- Any incapacitating psychiatric conditions, including significant history of substance abuse and severe depression
- Chronic treatment with medications that might modify cortical excitability
- Subjects with visual impediments that would limit our ability to obtain reliable testing
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Using Repetitive Transcranial Magnetic Stimulation (rTMS) in the Rehabilitation of Chronic Spatial Neglect After Stroke: A Double Blind Study
Visuospatial neglect is a common neurological symptom which appears following strokes on regions of the right hemisphere of the brain. It affects patient's self representation and awareness of the space, impairing functional rehabilitation and adaptation back to a normal life. The primary purpose of this protocol is to assess the impact of 10 daily sessions of a non-invasive brain stimulation technique, low frequency repetitive Transcranial Magnetic Stimulation (rTMS), applied on the intact hemisphere of the brain to treat post stroke visuospatial neglect at the chronic stage. The hypothesis is that a regime of real but not sham rTMS on the left posterior parietal cortex of the brain will long-lastingly ameliorate visuospatial neglect in stroke patients as revealed by clinical paper-and-pencil and computer-based tests assessing search, detection and discrimination of stimuli presented in different areas of the visual field.
Read the detailed description
Scientific aims and goals:
The long-term goal aim of this application is to provide evidence of the role of a non-invasive neuromodulation technique such as rTMS in the treatment of chronic neurological sequels generated after strokes in human patients. Such interventions are based in an "at will" modulation the level of activity in intact regions, resulting in an enhancement of excitatory projections or the suppression of inhibitory influences driven through spared connectivity. They result in activity increases of the stroke surviving neurons, allowing the re-emergence of function after brain damage. Such principles can be applied to different sorts of neurological sequels for which the underlying connectivity and its post-stroke status is well known. In this specific project, we propose the use of low frequency rTMS on the intact left posterior parietal cortex (in the intraparietal sulcus, IPS) to improve the symptoms of visuospatial neglect derived form right stroke injuries including the posterior parietal cortex. Such project is based in the interhemispheric rivalry hypothesis, according to which, spatial neglect is in part caused by the over inhibition exerted from the intact left parietal cortex onto the injured left homologue regions, which are mediated by well-known overall inhibitory transcallosal projections between the left and the right hemispheres. According to this hypothesis and preliminary data, the reduction of the left parietal disinhibition should result into a lesser degree of suppression exerted by the intact left hemisphere sites onto the right injured parietal areas, process which will along the emergence of activity.In this context, we defined a primary aim accompanied by two secondary aims, which will be tackled in parallel:Primary AIMS AIM1: To assess the effects of repetitive Transcranial Magnetic Stimulation (rTMS) in the treatment of chronic visuospatial neglect generated by stroke Secondary AIMS AIM 2: To assess the durability of such a recovery over time once the treatment is completed and discontinued AIM 3: To further assess the safety of such therapeutic approach based in the deactivation of an intact -but hyperexcited region- holding connectivity with the damaged area.
Evaluation criteria Main criteria -Changes in the Spatial Bias Compound Score (SBCS) between pre (baseline) and post 10 days of rTMS treatment Such score is calculated on the basis of the result of 4 subtests which include: (1) bells cancellation task, (2) a copy of the GAINOTTI figure, (3) identification of overlapping figures, and (4) line bisection, according to the following formula (SBCS=λ=ln(XR/XL), considering the identification or copying of elements presented on the right or the left visual fields of the patient. The subtests of the SBCS will be also individually assessed and followed.
Secondary criteria
- Efficacy criteria
- Safety criteria
- Predictive factors assessmentStudy population and duration of studyWe will study a population of stroke patients with chronic signs of hemispatial neglect with at least 3 months of evolution (n=148, 2 groups of 74 patients) recruited across 48 months at an approximate rate of 37 patients /year.
- Conditions
- Cerebrovascular Disorders, Cerebral Stroke, VISIO-spatial Neglect, VISUO-spatial Extinction
- Being tested
- Real rTMS, Sham rTMS
- Keywords
- Stroke, Visuospatial neglect, Visuospatial extinction, Transcranial Magnetic Stimulation (TMS), Non-invasive brain stimulation, Neuromodulation, Brain parietal cortex, Neurological sequels, Cognitive rehabilitation
- Medical subject headings
- Cerebrovascular Disorders, Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Real rTMSDevice
Transcranial Magnetic Stimulation, in a low frequency (1 Hz) continuous train of 20 minutes (1200 pulses)
Sham rTMSDevice
two TMS coils will be used: a passive one which is placed flat on top of the "actively" targeted region which remains unplugged and generates a continuous scalp tactile sensation, and an active one located at a prudential distance from the scalp, which will deliver active pulses and its accompanying sensations
| Study group | Role | What they receive |
|---|---|---|
| 1: Real rTMS treatment | Active comparator | Transcranial Magnetic Stimulation, in a low frequency (1 Hz) continuous train of 20 minutes (1200 pulses) Receives: Device: Real rTMS |
| 2: Sham rTMS treatment | Sham comparator | Simulation of rTMS Receives: Device: Sham rTMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in the Spatial Bias Compound Score (SBCS). Such score is calculated on the basis of the result of 4 subtests
Measured: between pre (baseline) and post 10 days of rTMS treatment
Secondary outcomes (12)
Changes in Catherine BERGEGO Scale and-or equivalent ecological test
Measured: between pre (baseline) and every subsequent evaluation
Changes in the percentage of correct target detections vs. total
Measured: between pre (baseline) and every subsequent evaluation
Changes in the Normalized reaction time of correct detections
Measured: between pre (baseline) and every subsequent evaluation
potential clinically relevant side-effect caused by the use of TMS in terms of neurological manifestations such as: seizure, occurrence of additional stroke, or signs of enhanced intracranial pressure.
Measured: During rTMS treatment and the 6 months follow-up
changes in cognitive functions processed by the intact left parietal cortex
Measured: between baseline and every subsequent evaluation, during the 6 months follow-up
Changes of the main cognitive domains and depression status according to the Mini-Mental test and Hamilton depression scale
Measured: between pre (baseline) and every subsequent evaluation
Correlation between treatment efficacy and lesion location and extent
Measured: Any time after the end of rTMS treatment
Correlation between treatment efficacy and severity of Neglect and other associated clinical deficits
Measured: Any time after the end of rTMS treatment
Correlation between treatment efficacy and rTMS parameters and patient's cortical excitability and sensations
Measured: Any time after the end of rTMS treatment
Correlation between treatment efficacy and daily activities with potential impact on Neglect
Measured: Any time after the end of rTMS treatment
Evaluation of SBCS and its subscores at each follow-up visits
Measured: 5 days, 10 days, 15 days, 20 days, 27 days, 40 days, 70 days, 130 days and 190 days after 1st rTMS session.
Changes in neurological conditions according to: Rankin, Barthel and NIH SS scores
Measured: Between baseline and every subsequent evaluation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2009 (estimated)
- Study start24 Mar 2010
- Primary completion15 Oct 2014
- Study completion15 Oct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cerebrovascular DisordersStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pascale PRADAT-DIEHL, MD-PhD, Study director, Assistance Publique - Hôpitaux de ParisAntoni VALERO-CABRE, MD-PhD, Principal investigator, Centre National de la Recherche Scientifique, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01000103
- Sponsor's protocol ID
- P071238
- Other IDs
- ID RCB 2009-A00280-57
- Acronym
- NEGLECT
- Status last verified
- Feb 2021
- First submitted
- 21 Oct 2009
- Last updated
- 25 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Using Repetitive Transcranial Magnetic Stimulation (rTMS) in the Rehabilitation of Chronic Spatial Neglect After Stroke: A Double Blind Study
- ClinicalTrials.gov ID
- NCT01000103
- Acronym / sponsor ID
- NEGLECT / P071238
- Conditions
- Cerebrovascular Disorders, Cerebral Stroke, VISIO-spatial Neglect, VISUO-spatial Extinction
- Keywords
- Stroke, Visuospatial neglect, Visuospatial extinction, Transcranial Magnetic Stimulation (TMS), Non-invasive brain stimulation, Neuromodulation, Brain parietal cortex, Neurological sequels
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 24 Mar 2010 (actual)
- Primary completion
- 15 Oct 2014 (actual)
- Study completion
- 15 Oct 2014 (actual)
- First posted
- 22 Oct 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Visuospatial neglect is a common neurological symptom which appears following strokes on regions of the right hemisphere of the brain. It affects patient's self representation and awareness of the space, impairing functional rehabilitation and adaptation back to a normal life. The primary purpose of this protocol is to assess the impact of 10 daily sessions of a non-invasive brain stimulation technique, low frequency repetitive Transcranial Magnetic Stimulation (rTMS), applied on the intact hemisphere of the brain to treat post stroke visuospatial neglect at the chronic stage. The hypothesis is that a regime of real but not sham rTMS on the left posterior parietal cortex of the brain will long-lastingly ameliorate visuospatial neglect in stroke patients as revealed by clinical paper-and-pencil and computer-based tests assessing search, detection and discrimination of stimuli presented in different areas of the visual field.
Detailed description
Scientific aims and goals:
The long-term goal aim of this application is to provide evidence of the role of a non-invasive neuromodulation technique such as rTMS in the treatment of chronic neurological sequels generated after strokes in human patients. Such interventions are based in an "at will" modulation the level of activity in intact regions, resulting in an enhancement of excitatory projections or the suppression of inhibitory influences driven through spared connectivity. They result in activity increases of the stroke surviving neurons, allowing the re-emergence of function after brain damage. Such principles can be applied to different sorts of neurological sequels for which the underlying connectivity and its post-stroke status is well known. In this specific project, we propose the use of low frequency rTMS on the intact left posterior parietal cortex (in the intraparietal sulcus, IPS) to improve the symptoms of visuospatial neglect derived form right stroke injuries including the posterior parietal cortex. Such project is based in the interhemispheric rivalry hypothesis, according to which, spatial neglect is in part caused by the over inhibition exerted from the intact left parietal cortex onto the injured left homologue regions, which are mediated by well-known overall inhibitory transcallosal projections between the left and the right hemispheres. According to this hypothesis and preliminary data, the reduction of the left parietal disinhibition should result into a lesser degree of suppression exerted by the intact left hemisphere sites onto the right injured parietal areas, process which will along the emergence of activity.In this context, we defined a primary aim accompanied by two secondary aims, which will be tackled in parallel:Primary AIMS AIM1: To assess the effects of repetitive Transcranial Magnetic Stimulation (rTMS) in the treatment of chronic visuospatial neglect generated by stroke Secondary AIMS AIM 2: To assess the durability of such a recovery over time once the treatment is completed and discontinued AIM 3: To further assess the safety of such therapeutic approach based in the deactivation of an intact -but hyperexcited region- holding connectivity with the damaged area.
Evaluation criteria Main criteria -Changes in the Spatial Bias Compound Score (SBCS) between pre (baseline) and post 10 days of rTMS treatment Such score is calculated on the basis of the result of 4 subtests which include: (1) bells cancellation task, (2) a copy of the GAINOTTI figure, (3) identification of overlapping figures, and (4) line bisection, according to the following formula (SBCS=λ=ln(XR/XL), considering the identification or copying of elements presented on the right or the left visual fields of the patient. The subtests of the SBCS will be also individually assessed and followed.
Secondary criteria
- Efficacy criteria
- Safety criteria
- Predictive factors assessmentStudy population and duration of studyWe will study a population of stroke patients with chronic signs of hemispatial neglect with at least 3 months of evolution (n=148, 2 groups of 74 patients) recruited across 48 months at an approximate rate of 37 patients /year.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1: Real rTMS treatment | Active comparator | Device: Real rTMSTranscranial Magnetic Stimulation, in a low frequency (1 Hz) continuous train of 20 minutes (1200 pulses) |
| 2: Sham rTMS treatment | Sham comparator | Device: Sham rTMSSimulation of rTMS |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Unilateral right hemisphere stroke
- Visuospatial neglect or extinction at the time of entry, as determined by at least 1 test of the battery (BEN) displaying pathological scores (cut off values as defined in AZOUVI et al. JNNP 2004, Table 1), or an ECB test, score > 8
- A period of evolution of at least 3 months since stroke event
- Age between 18 and 75 years old
- Affiliation to Social Security system
Key exclusion criteria (18 listed)
- Criteria related to the stroke:
- Criteria related to rTMS:
- Criteria related to feasibility:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Real rTMSTranscranial Magnetic Stimulation, in a low frequency (1 Hz) continuous train of 20 minutes (1200 pulses) | Device | 1: Real rTMS treatment |
| Sham rTMStwo TMS coils will be used: a passive one which is placed flat on top of the "actively" targeted region which remains unplugged and generates a continuous scalp tactile sensation, and an active one located at a prudential distance from the scalp, which will deliver active pulses and its accompanying sensations | Device | 2: Sham rTMS treatment |
Primary outcome
Changes in the Spatial Bias Compound Score (SBCS). Such score is calculated on the basis of the result of 4 subtests
Time frame: between pre (baseline) and post 10 days of rTMS treatment
12 secondary outcomes
Changes in Catherine BERGEGO Scale and-or equivalent ecological test
Time frame: between pre (baseline) and every subsequent evaluation
Changes in the percentage of correct target detections vs. total
Time frame: between pre (baseline) and every subsequent evaluation
Changes in the Normalized reaction time of correct detections
Time frame: between pre (baseline) and every subsequent evaluation
potential clinically relevant side-effect caused by the use of TMS in terms of neurological manifestations such as: seizure, occurrence of additional stroke, or signs of enhanced intracranial pressure.
Time frame: During rTMS treatment and the 6 months follow-up
changes in cognitive functions processed by the intact left parietal cortex
Time frame: between baseline and every subsequent evaluation, during the 6 months follow-up
Changes of the main cognitive domains and depression status according to the Mini-Mental test and Hamilton depression scale
Time frame: between pre (baseline) and every subsequent evaluation
Correlation between treatment efficacy and lesion location and extent
Time frame: Any time after the end of rTMS treatment
Correlation between treatment efficacy and severity of Neglect and other associated clinical deficits
Time frame: Any time after the end of rTMS treatment
Correlation between treatment efficacy and rTMS parameters and patient's cortical excitability and sensations
Time frame: Any time after the end of rTMS treatment
Correlation between treatment efficacy and daily activities with potential impact on Neglect
Time frame: Any time after the end of rTMS treatment
Evaluation of SBCS and its subscores at each follow-up visits
Time frame: 5 days, 10 days, 15 days, 20 days, 27 days, 40 days, 70 days, 130 days and 190 days after 1st rTMS session.
Changes in neurological conditions according to: Rankin, Barthel and NIH SS scores
Time frame: Between baseline and every subsequent evaluation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pascale PRADAT-DIEHL, MD-PhD study director
Assistance Publique - Hôpitaux de Paris
Antoni VALERO-CABRE, MD-PhD principal investigator
Centre National de la Recherche Scientifique, France
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Real rTMS in people with Cerebrovascular Disorders and Cerebral Stroke, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in the Spatial Bias Compound Score (SBCS). Such score is calculated on the basis of the result of 4 subtests (time frame: between pre (baseline) and post 10 days of rTMS treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2021.