Neurorehabilitation in Patients With Disorders of Consciousness: Multidimensional Ambispective Study on the Impact of Single and Combined Approaches
1 other identifier
observational
140
0 countries
N/A
Brief Summary
Disorders of consciousness (DOC), such as the vegetative state/unresponsive wakefulness syndrome (VS/UWS) and the minimally conscious state (MCS), represent severe clinical conditions arising from acquired brain injury (ABI), exerting a profound impact on patients, caregivers, and healthcare systems. The clinical heterogeneity, diagnostic challenges, and paucity of robust evidence on the comparative efficacy of rehabilitation interventions underscore the need for a deeper understanding of the underlying neurophysiological, cognitive, and biological mechanisms involved in consciousness recovery. This monocentric ambispective observational study aims to investigate the effects of advanced neurorehabilitation treatments-including multimodal sensory stimulation, non-invasive neuromodulation via transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS), and the use of augmentative and alternative communication (AAC) devices with eye-tracking-on various facets of residual consciousness in patients diagnosed with DOC admitted to the Neurorehabilitation Unit of the IRCCS Centro Neurolesi "Bonino Pulejo" in Messina. The study design encompasses the collection of clinical and rehabilitation data from hospitalized patients undergoing treatment, both retrospectively and prospectively. Specifically, data from patients admitted and treated in the 36 months preceding study initiation, as well as those admitted and treated in the subsequent 36 months, will be included. Upon data collection, participants will be classified a posteriori as "responders" or "non-responders" based on whether they meet at least one of the following criteria: (I) an increase of ≥3 points on the Coma Recovery Scale-Revised (CRS-R) from baseline or a clinically relevant state transition (e.g., VS/UWS → MCS; MCS → emergence from MCS \[EMCS\]); (II) an increase of ≥10 points on the Functional Independence Measure (FIM) or ≥0.5 standard deviations (SD) from baseline; (III) an increase of ≥10 points on the Barthel Index or ≥0.5 SD from baseline. The primary objective is to estimate the proportion of responders and non-responders at the end of training or hospitalization. Secondary objectives include identifying variables predictive of treatment response at the end of intervention (training type/modality, aetiology, demographic factors, comorbidities), quantifying the dose-response gradient (number of sessions/session duration versus response probability), and assessing changes in neurophysiological, physiological, and biological parameters collected during hospitalization (neuroimaging examinations, neurofilament light chain \[NfL\] assays, EEG/event-related potentials \[ERP\], skin conductance response, heart rate frequency and variability, and oculomotor activity). Data will be analysed using descriptive statistics appropriate to variable distributions. The primary endpoint, defined as the proportion of responders at the end of training/hospitalization, will be evaluated using logistic regression models in an as-treated approach, reporting odds ratios and marginal estimates (risk ratios and absolute risk differences) with 95% confidence intervals (CI). Confounding will be addressed through multivariable adjustment and propensity score-based methods (inverse probability of treatment weighting \[IPTW\]/overlap weighting). Continuous secondary outcomes will be analysed with linear models or linear mixed-effects models for repeated measures. Dose-response relationships will be explored, alongside sensitivity and subgroup analyses. All analyses will be performed using R software (version 4.4.2), employing two-sided tests with a significance level of α=0.05. The study will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice (GCP) guidelines.
Trial Health
Trial Health Score
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participants targeted
Target at P50-P75 for all trials
Started Jan 2026
Typical duration for all trials
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Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 7, 2026
CompletedStudy Start
First participant enrolled
January 16, 2026
CompletedFirst Posted
Study publicly available on registry
February 4, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 16, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 16, 2029
February 4, 2026
December 1, 2025
3 years
January 7, 2026
January 29, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Level of consciousness
CRS-R
From admission to 36 months or eventual discharge
Secondary Outcomes (1)
Neurorehabilitative training modalities
From baseline to 36 months/discharge
Other Outcomes (1)
Physiological response
From baseline to 36 months / discharge
Study Arms (1)
Responders
A patient is classified as a "responder" if they meet at least one of the following criteria relative to baseline: I. An increase of ≥3 points on the Coma Recovery Scale-Revised (CRS-R) or a clinically relevant state transition (e.g., VS/UWS → MCS; MCS → emergence from MCS \[EMCS\]). II. An increase of ≥10 points on the Functional Independence Measure (FIM) or ≥0.5 standard deviations (SD) from baseline. III. An increase of ≥10 points on the Barthel Index or ≥0.5 SD from baseline.
Interventions
Patients will undergo one or more of the specified rehabilitative treatments, depending on the medical prescriptions issued. All treatments are non-invasive in nature and are administered within the hospital facility. The methods of treatment delivery vary depending on the patient's condition.
Eligibility Criteria
Adult patients with a diagnosis of VS/UWS or MCS, admitted to the Neurorehabilitation/GCA Unit of the Piemonte/Casazza Hospital (IRCCS Centro Neurolesi Bonino-Pulejo) and treated according to clinical practice with one or more of the following non-invasive approaches, will be included: multimodal sensory stimulation (SS), tDCS, TMS, AAC devices with eye-tracking, standard physiotherapy/speech therapy.
You may qualify if:
- Diagnosis of VS/MCS following ABI, according to clinical and neuroradiological findings.
- Age between 18 and 90 years.
- Adequate pulmonary gas exchange function (PaO₂ / FiO₂ ratio ≥ 250).
- Stable haemodynamic profile (absence of significant arterial variations in mean arterial pressure and/or heart rate).
You may not qualify if:
- Diagnosis of DOC due to non-structural aetiopathogenesis.
- Having previously undergone multiple rehabilitation cycles
- Being affected by deafness and/or blindness
- Having unstable intracranial pressure values
- Having cerebral perfusion values below 60 mmHg
- Having other concomitant medical conditions that could interfere with the rehabilitation
Contact the study team to confirm eligibility.
Sponsors & Collaborators
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Davide Cardile, Psychologist
IRCCS Centro Neurolesi Bonino Pulejo
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- OTHER
- Target Duration
- 36 Months
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Psychologist
Study Record Dates
First Submitted
January 7, 2026
First Posted
February 4, 2026
Study Start
January 16, 2026
Primary Completion (Estimated)
January 16, 2029
Study Completion (Estimated)
January 16, 2029
Last Updated
February 4, 2026
Record last verified: 2025-12
Data Sharing
- IPD Sharing
- Will not share