Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Therapiezentrum Burgau | OTHER |
Not provided
Not provided
Not provided
Not provided
Not provided
Background:
Severe brain injury could cause chronic disorders of consciousness (DOC). Treating DOC patients to improve recovery remains very challenging. A few randomized controlled studies have been published in the recent years, focusing on non-invasive brain stimulation (NIBS) treatments to improve patients' neurobehavioural functioning. Among NIBS, repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that can modulate cortical excitability, enhance neural plasticity, and induce strong neuromodulatory effects that outlast the period of stimulation. It is thought to modulate cortical activity and could therefore be effective for treating DOC patients. Currently, there is no unified protocol for rTMS in DOC patients and studies vary in many aspects.
In this study, the investigators aim to improve the functional recovery of DOC patients following severe brain injury using rTMS in two multi-center double-blind studies.
Methods/design:
The investigators will recruit 90 DOC patients. Patients will have three rTMS sessions that will be randomized within patients in a crossover design: (i) one real stimulation on the left dorsolateral prefrontal cortex (DLPFC); (ii) one real stimulation on the left angular cortex (AG) and (iii) one sham stimulation. Sessions will be separated by at least 5 days washout period. Each stimulation session will last 20 minutes with a frequency of 20Hz (train duration: 4s; inter-train interval: 26s; 3200 pulses at 80% of the resting motor threshold - RMT). The RMT, i.e., the minimum stimulus intensity that generated a motor evoked potential response of at least 50μV at rest for 5 out of 10 trials, will be calculated for the stimulation target using single-pulses on the right abductor pollicis brevis muscle.
After an interval of one week, a parallel design study will begin. Ninety patients will be randomly divided in two experimental groups and one sham group (30 patients per group). Stimulation will be performed for 20 working days once a day with the same stimulation parameters as in the crossover study.
Primary outcome will be determined as behavioral response to treatment as measured using the Coma Recovery Scale - Revised (CRS-R). Resting-state high-density EEG will be also recorded to investigate the neurophysiological correlates by rTMS.
Discussion:
This study will contribute to define the role of rTMS for the treatment of DOC patients and characterise the neural correlates of its action. In addition, the investigators will define the responders' profile based on patients' characteristics and functional impairments and develop biomarkers of responsiveness using machine learning to categorize EEG signals according to clinical responsiveness to the treatment.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sham Stimulation Group for Crossover Study (DLPFC + AG) | Sham Comparator | Sham stimulation will be delivered on the dorsolateral prefrontal cortex (DLPFC) and on the angular cortex (AG) using a sham coil in the crossover study. |
|
| DLPFC Stimulation Group for Crossover Study | Active Comparator | Real stimulation will be delivered on the left dorsolateral prefrontal cortex (DLPFC) using a real coil in the crossover study. |
|
| AG Stimulation Group for Crossover Study | Active Comparator | Real stimulation will be delivered on the left angular cortex (AG) using a real coil in the crossover study. |
|
| Sham Stimulation Group for Parallel Study (DLPFC + AG) | Sham Comparator | Sham stimulation will be delivered on the dorsolateral prefrontal cortex (DLPFC) or on the angular cortex (AG) using a sham coil in the parallel study. |
|
| DLPFC Stimulation Group for Parallel Study | Active Comparator | Real stimulation will be delivered on the left dorsolateral prefrontal cortex (DLPFC) using a real coil in the parallel study. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sham Stimulation for Crossover Study | Device | Stimulation will be delivered on the dorsolateral prefrontal cortex (DLPFC) or the angular cortex (AG) using a sham coil for 20 minutes with a frequency of 20Hz (train duration: 4s; inter-train interval: 26s; 3200 pulses at 80% of the resting motor threshold ) in one session. A single session will be conducted. |
| Measure | Description | Time Frame |
|---|---|---|
| Change from Baseline Coma Recovery Scale - Revised for Crossover Study | The Coma Recovery Scale - Revised is a non-invasive behavioural examination. It contains 23 items hierarchically presented and divided in 6 sub-scales (auditory, visual, motor, oro-motor/verbal, communication and arousal). The score is based on presence or absence of behaviours in response to sensory stimulations. The quantitative score can be calculated by adding the best observed response in each sub-scale. The diagnosis is obtained from the quality of observed behaviours (e.g., the ability of visual tracking means that the patient is minimally conscious). The total score ranges between 0 and 23. Higher scores mean a better outcome. | immediately after each rTMS session |
| Change from Baseline Coma Recovery Scale - Revised for Parallel Study 1 | The Coma Recovery Scale - Revised is a non-invasive behavioural examination. It contains 23 items hierarchically presented and divided in 6 sub-scales (auditory, visual, motor, oro-motor/verbal, communication and arousal). The score is based on presence or absence of behaviours in response to sensory stimulations. The quantitative score can be calculated by adding the best observed response in each sub-scale. The diagnosis is obtained from the quality of observed behaviours (e.g., the ability of visual tracking means that the patient is minimally conscious). The total score ranges between 0 and 23. Higher scores mean a better outcome. | immediately after the last rTMS session |
| Change from Baseline Coma Recovery Scale - Revised for Parallel Study 2 | The Coma Recovery Scale - Revised is a non-invasive behavioural examination. It contains 23 items hierarchically presented and divided in 6 sub-scales (auditory, visual, motor, oro-motor/verbal, communication and arousal). The score is based on presence or absence of behaviours in response to sensory stimulations. The quantitative score can be calculated by adding the best observed response in each sub-scale. The diagnosis is obtained from the quality of observed behaviours (e.g., the ability of visual tracking means that the patient is minimally conscious). The total score ranges between 0 and 23. Higher scores mean a better outcome. |
| Measure | Description | Time Frame |
|---|---|---|
| Change from Baseline Resting-State EEG for Crossover Study 1 | EEG will be collected using a high-density EEG. Fifteen minutes of resting state will be performed. Resting-state EEG complexity and connectivity analyses will be performed at the individual and group level. The investigators will compute spectral measures as well as cortical functional connectivity using median spectral connectivity and graph-theoretic topology metrics such as clustering coefficient, path length, modularity and participation coefficient. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
-
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Masachika Niimi, M.D., Ph.D. | Contact | +32494999230 | m.niimi@uliege.be | |
| Olivia Gosseries, Ph.D. | Contact | +3243663954 | ogosseries@uliege.be |
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital of Liège | Liège | 4000 | Belgium |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37545735 | Derived | Vitello MM, Rosenfelder MJ, Cardone P, Niimi M, Willacker L, Thibaut A, Lejeune N, Laureys S, Bender A, Gosseries O. A protocol for a multicenter randomized and personalized controlled trial using rTMS in patients with disorders of consciousness. Front Neurol. 2023 Jul 21;14:1216468. doi: 10.3389/fneur.2023.1216468. eCollection 2023. |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D003244 | Consciousness Disorders |
| ID | Term |
|---|---|
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| D018592 | Cross-Over Studies |
| ID | Term |
|---|---|
| D015340 | Epidemiologic Research Design |
| D004812 | Epidemiologic Methods |
| D008919 | Investigative Techniques |
| D017531 | Health Care Evaluation Mechanisms |
Not provided
Not provided
We will perform a 3 arm crossover trial. Subsequently, we will perform a longer protocol using a 3 arm parallel design.
Not provided
Not provided
Not provided
|
| AG Stimulation Group for Parallel Study | Active Comparator | Real stimulation will be delivered on the left angular cortex (AG) using a real coil in the parallel study. |
|
|
| DLPFC Stimulation for Crossover Study | Device | Stimulation will be delivered on the left dorsolateral prefrontal cortex (DLPFC) using a real coil for 20 minutes with a frequency of 20Hz (train duration: 4s; inter-train interval: 26s; 3200 pulses at 80% of the resting motor threshold ) in one session. A single session will be conducted. |
|
| AG Stimulation for Crossover Study | Device | Stimulation will be delivered on the left angular cortex (AG) using a real coil for 20 minutes with a frequency of 20Hz (train duration: 4s; inter-train interval: 26s; 3200 pulses at 80% of the resting motor threshold ) in one session. A single session will be conducted. |
|
| Sham Stimulation for Parallel Study | Device | Stimulation will be delivered on the dorsolateral prefrontal cortex (DLPFC) or the angular cortex (AG) using a sham coil for 20 minutes with a frequency of 20Hz (train duration: 4s; inter-train interval: 26s; 3200 pulses at 80% of the resting motor threshold ) in one session. Twenty sessions will be conducted. |
|
| DLPFC Stimulation for Parallel Study | Device | Stimulation will be delivered on the left dorsolateral prefrontal cortex (DLPFC) using a real coil for 20 minutes with a frequency of 20Hz (train duration: 4s; inter-train interval: 26s; 3200 pulses at 80% of the resting motor threshold ) in one session. Twenty sessions will be conducted. |
|
| AG Stimulation for Parallel Study | Device | Stimulation will be delivered on the left angular cortex (AG) using a real coil for 20 minutes with a frequency of 20Hz (train duration: 4s; inter-train interval: 26s; 3200 pulses at 80% of the resting motor threshold ) in one session. Twenty sessions will be conducted. |
|
| 1 week after the last rTMS session |
| Change from Baseline Coma Recovery Scale - Revised for Parallel Study 3 | The Coma Recovery Scale - Revised is a non-invasive behavioural examination. It contains 23 items hierarchically presented and divided in 6 sub-scales (auditory, visual, motor, oro-motor/verbal, communication and arousal). The score is based on presence or absence of behaviours in response to sensory stimulations. The quantitative score can be calculated by adding the best observed response in each sub-scale. The diagnosis is obtained from the quality of observed behaviours (e.g., the ability of visual tracking means that the patient is minimally conscious). The total score ranges between 0 and 23. Higher scores mean a better outcome. | 2 week after the last rTMS session |
| during each rTMS session |
| Change from Baseline Resting-State EEG for Crossover Study 2 | EEG will be collected using a high-density EEG. Fifteen minutes of resting state will be performed. Resting-state EEG complexity and connectivity analyses will be performed at the individual and group level. The investigators will compute spectral measures as well as cortical functional connectivity using median spectral connectivity and graph-theoretic topology metrics such as clustering coefficient, path length, modularity and participation coefficient. | immediately after each rTMS session |
| Change from Baseline Resting-State EEG for Parallel Study 1 | EEG will be collected using a high-density EEG. Fifteen minutes of resting state will be performed. Resting-state EEG complexity and connectivity analyses will be performed at the individual and group level. The investigators will compute spectral measures as well as cortical functional connectivity using median spectral connectivity and graph-theoretic topology metrics such as clustering coefficient, path length, modularity and participation coefficient. | immediately after the last rTMS session |
| Change from Baseline Resting-State EEG for Parallel Study 2 | EEG will be collected using a high-density EEG. Fifteen minutes of resting state will be performed. Resting-state EEG complexity and connectivity analyses will be performed at the individual and group level. The investigators will compute spectral measures as well as cortical functional connectivity using median spectral connectivity and graph-theoretic topology metrics such as clustering coefficient, path length, modularity and participation coefficient. | 1 week after the last rTMS session |
| Change from Baseline Resting-State EEG for Parallel Study 3 | EEG will be collected using a high-density EEG. Fifteen minutes of resting state will be performed. Resting-state EEG complexity and connectivity analyses will be performed at the individual and group level. The investigators will compute spectral measures as well as cortical functional connectivity using median spectral connectivity and graph-theoretic topology metrics such as clustering coefficient, path length, modularity and participation coefficient. | 2 week after the last rTMS session |
| Therapiezentrum Burgau | Burgau | 89331 | Germany |
|
| D013568 | Pathological Conditions, Signs and Symptoms |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D011787 | Quality of Health Care |
| D017530 | Health Care Quality, Access, and Evaluation |
| D011634 | Public Health |
| D004778 | Environment and Public Health |