Clinical Trials Logo

Clinical Trial Summary

Severe Acquired Brain Injury is defined as a traumatic, post-anoxic, vascular or other brain damage that causes coma for at least 24 hours and leads to permanent disability with sensorial, motor, cognitive or compartmental impairment. In this context, an accurate characterization of individual patients' profile in terms of neuronal damage, potential for neuroplasticity, neurofunctional and clinical state could allow to plan tailored rehabilitation and care pathway on the basis of solid prognostic information, also for optimizing resources of the National Health care systems and enhance ethical decisions. Patient profiling should encompass measures and procedures easily available at the bedside, and with affordable time, resource, and money-costs to determine a real impact on National Health systems. The aim of the study is identifying patient profiles in terms of clinical, neurophysiological and genetical aspects with better long-term outcome in order to plan tailored therapeutic interventions.


Clinical Trial Description

Background:

After a severe Acquired Brain Injury (sABI) the consciousness, the functional and the cognitive recovery of the patients depends on the severity of the damage suffered but also on the vulnerability of the individual brain. Some patients with sABI may survive in a state of Disorder of Consciousness (DoC) condition (i.e., patients in vegetative state/unresponsive wakefulness syndrome, VS/UWS or in minimally conscious state, MCS). Other patients, despite having a complete recovery of consciousness, can reach very variable degrees of functional and cognitive autonomy. The prognostic factors of consciousness recovery of patients with DoCs have been thoroughly investigated. Most of these studies investigated the acute phase, while only a few studies have examined the role of early clinical factors emerging before the complete recovery of consciousness . Further prognostic insights can be provided by analysis of genes coding for Apolipoprotein E (APOE), dopamineD2 receptor (DRD2), and Brain Derived Neutrophic Factors (BDNF), and by markers of axonal injury.

Study aim:

The present project aims at identifying patient profiles with better long-term outcome in order to plan tailored therapeutic interventions.

The patient profiles will be drawn up by gathering patient's demographic (age, gender, social and educational level), anamnestic (aetiology and time post-brain injury, Cognitive Reserve Index), clinical state (Cumulative Illness Rating Scale (CIRS), CRS-R total score and corresponding consciousness state; Disability Rating Scale, DRS, Functional Oral Intake Scale; FOIS, Glasgow Outcome Scale Expanded; GOS-E, Level of Cognitive Functioning; LCF) and neurophysiological data (Electroencephalogram (EEG), Somatosensory evoked potentials (SEP), and Motor evoked potentials (MEP) nerve conduction aimed at evaluating occurrence of critical illness polyneuropathy and myopathy (CIPNM)) at study entry (baseline), together with neural biomarkers (genetic markers).

On the basis of the above mentioned stratification of patients by this multimodal approach, the present study aimed to

1. Investigate the possible association of certain profiles with the consciousness recovery at the time of discharge from the Intensive Rehabilitation Unit (IRU), at 1 year and 2 years from the acute event

2. Investigate the possible association of certain profiles with the functional outcomes at the time of discharge from the Intensive Rehabilitation Unit (IRU), at 1 year and 2 years from the acute event.

3. Investigate the possible association of certain profiles with the long-term cognitive profile and the level of familiar and social participation at 1 year and 2 years from the acute event.

Setting , population and methods:

The proposed study is a longitudinal multi-location prospective observational cohort study.

Four centers of the Don Carlo Gnocchi Foundation will participate (Florence, La Spezia, Milan and Sant'Angelo dei Lombardi and the neurogenetics laboratory of the University of Florence, Department of Medical and Experimental Sciences, Neurology). The enrollment phase will last 3 years (June 2020-June 2023). 520 patients with severe brain injury will be included (200 for the Florence and La Spezia units and 60 for the Milan and Sant'Angelo dei Lombardi units).

All patients admitted in the participant IRU with a history of sABI within 4 months, aged 18+, presenting a signed informed consent signature for the participation to the study and for the genetic analysis will be consecutively enrolled.

A multidimodal evaluation including clinical examinations and neurophysiological assessments will be performed by skilled professionals. The study foresees four steps in the late acute phase and two in the long-term phase: 1) at the study entry time (T0), 2) at three months from T0 (T1) 3) at 6 months from T0 (T2) 4) at discharge (T3) 5) at 12 months from the acute event (T4) 6) at 24 months from the acute event.

Clinical assessment including :

1. Consciousness assessment using CRS-R

2. Care severity profile: including the comorbidity assessed thought the Cumulative Illness Rating Scale (CIRS), the presence of medical devices, sepsis occurrence during the IRU stay, neurosurgery interventions, bedsores, epileptic event and other complications

3. Functional evaluation using the following scales: ERBI, GOS-E, DRS, FIM, PAINED pain scale, TCT, Ashworth, FOIS

4. Neurocognitive profile evaluation using the Galveston Orientation and Amnesia Test (GOAT), the Level of Cognitive Functioning (LCF) and the International Classification of Functioning, Disability and Health (ICF), ABS, AES and Cognitive Reserve Index (CRI)

Multimodal neurophysiological evaluation including:

1. Standard EEG recording at rest. EEG background activity and reactivity will be classified according to recently proposed diagnostic criteria for DoC and to American Clinical Neurophysiology Society Critical Care EEG Terminology.

2. Motor and sensory nerve conduction studies. Sensory nerve action potentials, and compound muscle action potentials (CMAP) will be evaluated. Muscular activity at rest and when possible during reflex contraction will be assessed.

3. PEM: Transcranial magnetic stimulation (TMS) will be performed according to the standard criteria of the International Federation of Clinical Neurophysiology. MEP will be recorded from abductor digiti minimi and tibialis anterior muscles and size of MEP measured as MEP/CMAP amplitude ratio.

4. Bilateral upper limb SEP will be recorded according to the International Federation of Clinical Neurophysiology. The presence or absence of N20/P25 cortical components will be evaluated.

Genetic assessment Genomic DNA will be obtained from EDTA-whole venous blood sample by Automated Systems QiaCube (Qiagen). The genetic analysis of 5 different single nucleotide polymorphisms on ApoE, BDNF and DRD2 genes will be performed by high resolution melt (HRM) analyses and direct sequencing on Automatic Genetic Analyzer. APOE genotypes will be investigated by HRM with two sets of PCR primers designed to amplify the regions encompassing rs7412 [NC_000019.9: g.45412079C>T] and rs429358 (NC_000019.9: g.45411941T>C). The samples with known ApoE genotypes, which had been validated by DNA sequencing, will be used as standard references. The genetic polymorphism data will be compared to sex- and age-matched control of the DNA banking of the neurogenetic Laboratory of Careggi Hospital of Florence.

Statistic analysis:

All collected data will be analyzed using a machine learning algorithm, creating, for each patient, a risk profile for the possible consciousness recovery and functional autonomy.

On the basis of the results of this study, partecipant will build on a "decision support tool" for future sABI patients afferent to the Intensive Rehabilitative Unit, in order to plan personalized rehabilitative and therapeutic interventions, allowing therefore an optimization of resources (costs and resources) for National Health Service ;


Study Design


Related Conditions & MeSH terms


NCT number NCT04495192
Study type Observational [Patient Registry]
Source Fondazione Don Carlo Gnocchi Onlus
Contact Bahia Hakiki, MD, Phd
Phone 0039-333-4018388
Email bhakiki@dongnocchi.it
Status Recruiting
Phase
Start date June 9, 2020
Completion date June 10, 2025

See also
  Status Clinical Trial Phase
Enrolling by invitation NCT05542108 - Adding Motion to Contact: A New Model for Low-cost Family Centered Very-early Onset Intervention in Very Preterm-born Infants N/A
Completed NCT03400904 - Extubation Strategies in Neuro-Intensive Care Unit Patients and Associations With Outcome.
Completed NCT06073145 - Transcranial Doppler Using Wearable Ultrasound Patch
Recruiting NCT03899532 - Remote Ischemic Conditioning in Traumatic Brain Injury N/A
Recruiting NCT06010823 - Safety and Efficacy Evaluation of the Robotic Enhanced Error Training of Upper Limb Function in Post-stroke and Post TBI Participants N/A
Not yet recruiting NCT05833568 - Five-day 20-minute 10-Hz tACS in Patients With a Disorder of Consciousness N/A
Withdrawn NCT04288076 - The Brain and Lung Interaction (BALI) Study N/A
Completed NCT03162484 - Physical Activity and Chronic Acquired Brain Injury N/A
Not yet recruiting NCT02756585 - Computed Tomography Perfusion in Patients With Severe Head Injury N/A
Terminated NCT01430988 - Observational Study of the BrainScope® Ahead™ M-100 in UK Emergency Department Patients With Head Injury N/A
Completed NCT01093053 - Mind-Body Skills Groups for the Treatment of War Zone Stress in Military and Veteran Populations N/A
Completed NCT00975338 - The LETS Study: A Longitudinal Evaluation of Transition Services
Completed NCT00878631 - Feasibility Trial of Traumatic Brain Injured Patients Randomized in the Prehospital Setting to Either Hypertonic Saline and Dextran Versus Normal Saline Phase 2/Phase 3
Completed NCT03166722 - Cerebral Regional Tissue Oxygen Saturation to Guide Oxygen Delivery in Preterm Neonates During Immediate Transition N/A
Not yet recruiting NCT04478812 - Tbit System Precision and Correlation of Different Blood Samples N/A
Recruiting NCT05443542 - VIrtual Reality in Cognitive Rehabilitation of Processing Speed for Persons With ABI N/A
Recruiting NCT05309005 - Virtual Reality and Social Cognition After Acquired Brain Injury
Completed NCT02702635 - Measuring Blood Flow Characteristics Using Dynamic Contrast Enhanced Magnetic Resonance Imaging N/A
Withdrawn NCT04247321 - Non-invasive Near-infrared Spectroscopy (NIRS) Versus Invasive Licox Intracranial Pressure N/A
Not yet recruiting NCT04386525 - Omega 3 and Ischemic Stroke; Fish Oil as an Option Phase 4