Clinical Trials Logo

Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT06323031
Other study ID # Blink-DoC
Secondary ID
Status Not yet recruiting
Phase
First received
Last updated
Start date May 2024
Est. completion date November 2025

Study information

Verified date March 2024
Source Fondazione Don Carlo Gnocchi Onlus
Contact Anna Estraneo, MD
Phone 3396418648
Email aestraneo@dongnocchi.it
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

Differential diagnosis between Unresponsive Wakefulness Syndrome (UWS) and Minimally Conscious State (MCS) is complicated due to severe cognitive and/or sensorimotor deficits in these patients. In this study the investigators aimed at exploring the diagnostic and prognostic validity of spontaneous eye blinking parameters (rate, amplitude, duration, variability) in a sample of patients with Disorders of Consciousness (DoC). This is a multi-center prospective observational study conducted in patients with Severe Acquired Brain Injury (sABI) and DoC admitted to 8 European participating centers, with clinical data collection not deviating from routine practice. The study is non-commercial and will have a maximum total duration of 24 months.


Description:

Observational, multicenter, longitudinal study. In this study, all patients admitted to the nine participating centers with diagnosis of DoC, and meeting the inclusion/exclusion criteria, will be enrolled. The admission of a patient to the research program is subject to the signing of an informed consent by the legal representative/primary caregiver of the patient. The representative will be informed about the study and its objectives, and an informational sheet will be provided. Population All patients with DoC after sABI consecutively admitted to participating centers who meet the inclusion/exclusion criteria (see below). Sample size On the basis of the effect size found in a previous study regarding the diagnostic value of eye blink rate (d=0.68), it is planned to enroll 58 patients with DoC (power=0.8; α=0.05) + an additional 20% to cope with possible drop-outs, for a total of 70 patients (23 in UWS, 23 in MCS minus; 23 in MCS plus; about 9 patients per center). For the secondary outcomes (i.e., diagnostic and prognostic value of further blink features) there is no previous data in the literature. In addition, a sample of 23 healthy individuals, balanced in terms of sex and age with the patient sample, will be enrolled as a reference group. Data collection procedure Within two weeks from study entry, patients will undergo two 20-minute resting electroencephalogram-electrooculogram (EEG-EOG) examinations, separated by 24 hours. Sessions will take place, following standard nursing procedures, between 10:00 AM and 5:00 PM, a time window minimally influenced by circadian peaks of drowsiness in patients with DoC, and a period during which it is believed that EBR is stable in healthy individuals. The EEG-EOG recording will be conducted at the patient's bedside or, if possible, on their wheelchair, with the patient awake (i.e., eyes open), maintaining a quiet and dimly lit environment. If the patient's arousal level is insufficient, the Coma Recovery Scale-Revised (CRS-R) arousal facilitation protocol will be administered; if the patient continues to keep their eyes closed, the recording session will be postponed to the next available day. During each session, the experimenter is positioned beside the patient, out of her/his visual field. Blinks will be detected in the EOG and defined as a sharp positive peak followed by a negative deflection within a time window of less than 400 ms. To assess the level of consciousness at the time of the EEG-EOG recordings, a CRS-R will be administered at the end of each session. To prevent the patient's awareness of the blink recording from affecting their blink rate, the patient is not informed about the blink recording during the EEG-EOG session but is simply encouraged to remain relaxed with eyes open and not to move. This procedure is carried out independently of the patient's clinical diagnosis. A follow-up assessment is planned at 6 months from T0 (T1). The healthy volunteers will also perform two resting EEG-EOG examinations, each lasting 20 min, 24 h apart. EEG will be recorded by at least 19 electrodes placed on the patients' scalp according to the international 10-20 system (Fp1, Fp2, F7, F8, F3, F4, C3, C4, T3, T4, P3, P4, T5, T6, O1, O2, Fz, Cz, Pz) + vertical EOG electrodes, referenced to the vertex. Impedance will be kept below 5 kΩ for electrodes covering the cortex as well as for EOG electrodes. Data will be sampled at a 1000-Hz rate and band pass filtered between 0.1 Hz and 30 Hz; a notch filter will be used to eliminate frequencies around 50 Hz for online visualization. If the EEG recording in a session presents a considerable number of artefacts, the acquisition will be repeated within the next available day. Enrollment duration: 12 months Study duration: about 24 months. Statistical plan Patient characteristics at study entry will be compared between the diagnostic groups (UWS, MCS minus, MCS plus) through parametric or non-parametric univariate analyses, as deemed appropriate after verification of data distribution. Similarly, univariate analyses will be performed to compare eye blink rate (EBR) and additional blink features between diagnostic groups. Univariate within-subject analyses will be performed to compare EBR and additional blink features across time. In addition, correlation analyses will be performed to verify the existence of a relationship between blink features and level of consciousness as measured by the total score of the CRS-R. If so, logistic regression models will be implemented with blink features and demographic and anamnestic variables as predictors, and outcome as dependent variable. The results will be considered statistically significant if p<05.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 70
Est. completion date November 2025
Est. primary completion date May 2025
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - clinical diagnosis of DoC (UWS, MCS minus, MCS plus) following repeated clinical evaluation (at least four CRS-R in a week) - age = 18 years - time post-onset =6 months - Previous sABI of any etiology (traumatic, vascular, anoxic, mixed, etc.) - Negative anamnesis for neurological or psychiatric disorders. Exclusion Criteria: - unstable clinical conditions (e.g. respiratory failure, fever, status epilepticus, etc.); - ophthalmic diseases, or clinically detected peripheral damage in eyelid motility (e.g. orbital fracture); - intake of sedative drugs in the preceding 24 hours; - additional brain event following admission (e.g., stroke).

Study Design


Related Conditions & MeSH terms


Locations

Country Name City State
Belgium Coma Science Group, GIGA-Consciousness, University of Liege Liege
Germany Therapiezentrum Burgau Burgau
Germany Dipartimento di Neurologia, LMU Hospital, LMU Munich Munich
Italy Unità Gravi Cerebrolesioni - Dipartimento Neuroscienze - Azienda Ospedaliera - Universitaria Ferrara Ferrara
Italy IRCCS Fondazione Don Gnocchi ONLUS Florence
Italy IRCCS Santa Maria Nascente Fondazione Don Gnocchi ONLUS Milan
Italy Polo Specialistico Riabilitativo Fondazione Don Carlo Gnocchi ONLUS Sant'Angelo dei Lombardi AV
Spain Instituto de Rehabilitación Neurológica IRENEA Valencia

Sponsors (7)

Lead Sponsor Collaborator
Fondazione Don Carlo Gnocchi Onlus Azienda Ospedaliera Universitaria Ferrara, Ludwig-Maximilians - University of Munich, Therapiezentrum Burgau, University Hospital Munich, University of Liege, VITHAS Valencia (Spain)

Countries where clinical trial is conducted

Belgium,  Germany,  Italy,  Spain, 

References & Publications (3)

Barbato G, Ficca G, Muscettola G, Fichele M, Beatrice M, Rinaldi F. Diurnal variation in spontaneous eye-blink rate. Psychiatry Res. 2000 Mar 6;93(2):145-51. doi: 10.1016/s0165-1781(00)00108-6. — View Citation

Magliacano A, Rosenfelder M, Hieber N, Bender A, Estraneo A, Trojano L. Spontaneous eye blinking as a diagnostic marker in prolonged disorders of consciousness. Sci Rep. 2021 Nov 17;11(1):22393. doi: 10.1038/s41598-021-01858-3. — View Citation

Wislowska M, Del Giudice R, Lechinger J, Wielek T, Heib DPJ, Pitiot A, Pichler G, Michitsch G, Donis J, Schabus M. Night and day variations of sleep in patients with disorders of consciousness. Sci Rep. 2017 Mar 21;7(1):266. doi: 10.1038/s41598-017-00323- — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Clinical Diagnosis Clinical diagnosis as assessed by the Coma Recovery Scale-Revised (min. - max- score = 0-23, with higher scores indicating a higher level of consciousness) 6 months from enrollment
See also
  Status Clinical Trial Phase
Recruiting NCT06076733 - Intervention Effect of Transcranial Alternating Current Stimulation (tACS) on Disorder of Consciousness (DOC) N/A
Recruiting NCT05558670 - Brain Network Characteristics in Patients With Disorders of Consciousness
Completed NCT02424656 - Alterations in the Brain's Connectome After Severe Traumatic Brain Injury
Completed NCT02879565 - Families Expectations and Hope Raised by an Evaluation of Consciousness in Patients in a Vegetative State N/A
Completed NCT02759068 - Beneficial Effects of Preference on Behavior in DOC Patients (COGNICOMA) N/A
Terminated NCT02732288 - Exploratory Study of Melatonin Induced Sleep Regularization in Severe Brain Injury N/A
Recruiting NCT06343415 - Robot-assisted Training After Traumatic Brain Injury and Disorders of Consciousness N/A
Completed NCT06403176 - Arteriovenous Plasma Multiomics in Patients With Disorders of Consciousness
Completed NCT03115021 - Neurophysiological Effects of tPCS and tDCS on Patients With Disorders of Consciousness Phase 1
Not yet recruiting NCT06167200 - Validation of a Clinical Complications Scale (CCS) in Patients With Disorders of Consciousness
Not yet recruiting NCT06464549 - Spontaneous Eye Blinking Evaluation for Cognitive Assessment of Individuals With Severe Acquired Brain Injury
Recruiting NCT04798456 - Aiming for a Better Understanding and Improvement of the Diagnosis and Prognosis of Patients With Disorders of Consciousness Through Multimodal Observations
Recruiting NCT04706689 - Development and Validation of the SWADOC Tool
Not yet recruiting NCT06426602 - mindBEAGLE: Unlocking Functional Communication for Patients With Disorders of Consciousness N/A
Completed NCT02394691 - Effect of Repeated tDCS Sessions on Cognitive Improvement in Patients With Disorders of Consciousness N/A
Not yet recruiting NCT02628639 - Optimizing the Evaluation of Awareness in Disorders of Consciousness N/A
Completed NCT02639481 - Erigo®Pro Coma Outcome Study - Study on the Effectiveness of a Robotic Tilt Table Device for Recovery of Consciousness Phase 3
Completed NCT02626403 - Fronto-parietal tDCS in Severely Brain Injured Patients With Disorders of Consciousness N/A
Completed NCT02930213 - The Core Body Temperature Rhythms: Distinguishing MCS From UWS Phase 2
Completed NCT01673126 - Transcranial Direct Current Stimulation in Patients With Disorders of Consciousness Phase 2