Intensive Neurowave Emotional Stimulation (INES) (INES_ABI)

Intensive Neurowave Emotional Stimulation (INES): A Pioneering RCT Investigating Cognitive-Motor Impact in Consciousness Disorders Post Severe Brain Injury

This is a randomized and controlled pilot study investigating the effects of intensive emotional stimulation with neurological waves (INES) on cognitive-motor functions in patients diagnosed with Vegetative State (VS) and Minimally Conscious State (MCS) following severe brain injury. The study aims to enroll at least 20 patients aged between 18 and 65 over 18 months. Patients will be recruited from the Neurorehabilitation Unit of Piedmont Hospital, IRCCS Centro Neurolesi Bonino Pulejo in Messina. The experimental group will receive multisensory stimulation using Neurowave (INES) for four weeks, five days a week, 45 minutes per session. The control group will undergo a traditional multisensory stimulation program.

Enrollment will use simple random sampling to minimize bias. Caregivers will provide biographical information, and both groups will be monitored using event-related potentials. Clinical scales will evaluate cognitive-motor outcomes at different time points. The study includes a one-month follow-up to assess long-term results. Data will be collected and exported for statistical analysis.

Study Overview

• Status: Completed
• Conditions: Disorders of Consciousness
• Intervention / Treatment: Device: Intensive Neurowave Emotional Stimulation (INES); Other: Intensive Sensorial Emotional Stimulation (ISES)

Detailed Description

This study aims to investigate the cognitive-motor effects of emotionally significant advanced multisensory stimulation (INES) in patients diagnosed with Vegetative State (VS) and Minimally Conscious State (MCS) following severe acquired brain injury. Primary objectives include exploring short- and long-term efficacy through clinical-psychometric follow-up and examining potential correlations between neurophysiological and clinical-psychometric parameters as predictive indices of recovery.

The secondary objectives concern the implementation of highly specialized technological innovations in current clinical practice, and evaluating the rehabilitation effectiveness of advanced treatment with Neurological Waves.

Therefore, the study aims to develop models and protocols for multisensory rehabilitation stimulation and evaluate the synergies between different stimulation modalities and advanced cognitive electrophysiology techniques. Furthermore, the research aims to promote clinical investigations and systematic monitoring of post-acute patients, focusing on the quantitative analysis of EEG and Cognitive Evoked Potentials to unconventional sensory stimuli with emotionally significant content. The study also deepens the understanding of the role of the metabolic-nutritional state in the cognitive-motor recovery of patients with disorders of consciousness.

The present study is a randomized controlled pilot study, with an interventional, non-pharmacological, and single-center design.

Materials and methods:

The study will consecutively enroll at least 20 adult subjects diagnosed with disorders of consciousness at the Neurorehabilitation Unit of the Piedmont Hospital. Comprehensive multidimensional assessments will be conducted at baseline (T0), followed by an intensive one-month course of advanced multisensory training using Neurowave (INES) for the experimental group and conventional multisensory stimulation (ISES) for the control group. Evaluation at the end of each training cycle (T1) and a one-month follow-up (T2) will provide information on long-term results.

Inclusion criterion:

Participants must be between the ages of 18 and 65, with a Glasgow Coma Scale (GCS) score greater than 8 and a Cognitive Scale Level (LCF) between 1 and 3. Informed consent must be obtained from their legal guardian.

Exclusion criteria:

Exclusion criteria include individuals outside the specified age range, lack of legal guardian consent, anatomical alterations that prevent the correct placement of electrodes, and absence of neurophysiological responses in visual and auditory evoked potentials.

Registration start and end dates:

The study implementation period is expected to be from December 2023 to March 2025, with a total study duration of 18 months.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Italy/Messina
    • Messina, Italy/Messina, Italy, 98124
      • IRCCS Centro Neurolesi Bonino Pulejo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age between 18 and 65 years.
• Glasgow Coma Scale (GCS) > 8.
• Level of Cognitive Scale (LCF) = 1-3.
• Consent is signed by the legal guardian.

Exclusion Criteria:

• Age < 18 years or > 65 years.
• Lack of consent from the legal guardian.
• Patients with cranial anatomical alterations hindering proper electrode, headset, etc., placement.
• Patients showed no neurophysiological responses in visual evoked potentials (VEP) and no V wave in auditory evoked potentials (AEP).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; patients will receive Neurowave multisensory stimulation with concurrent event-related potential acquisition. This intensive training spans five days a week over four weeks, with each session lasting 45 minutes, summing up to 20 sessions. During each session, participants will encounter personalized visual and auditory stimuli. Neurowave treatment comprises an intensive intervention, presenting emotionally significant audio-visual content linked to the patient's life history. Within Neurowave use, visual stimuli will be complemented by primary auditory stimulation, involving exposure to emotionally charged everyday sounds.	Device: Intensive Neurowave Emotional Stimulation (INES); Patients will undergo Neurowave-assisted multisensory stimulation five days a week for four weeks, featuring emotionally significant audio-visual content tied to personal history. Control group participants will experience primary auditory stimulation through familiar sounds, following a traditional rehabilitation approach mimicking the experimental group's frequency and intensity but without Neurowave use. This allows for a meaningful comparison of the two groups' experiences.; Other Names: Intensive Sensorial Emotional Stimulation (ISES)
Active Comparator: Control group; Participants will receive primary auditory stimulation featuring familiar and emotionally evocative everyday sounds. This involves exposure to audio tapes and sounds related to their daily life, including voices of family and friends, snippets of favorite songs, and sounds associated with past work or leisure activities. The control group will undergo a program called Intensive Sensorial Emotional Stimulation (ISES), matching the frequency, intensity, and session duration of the experimental group but without Neurowave system utilization. Distinctively, the control group will not utilize Neurowave technology. Instead, they will follow a traditional rehabilitation approach incorporating paper materials, live photos, face-to-face interaction with the therapist, and the conventional listening of music tapes. This method aims to replicate an emotionally engaging environment, serving as a comparative reference to the experimental group's Neurowave-assisted experience.	Other: Intensive Sensorial Emotional Stimulation (ISES); The Intensive Sensorial Emotional Stimulation (ISES) in the control group involves primary auditory stimulation with emotionally rich everyday sounds, including familiar voices, favorite songs, and sounds related to daily life and past activities. It mimics the experimental group's frequency and intensity, lasting 45 minutes per session, five days a week, for four weeks. Unlike the experimental group using Neurowave, the control group follows a traditional rehabilitation approach with paper materials, live photos, face-to-face interaction, and classic music tapes, facilitating a meaningful comparison between the two groups' experiences.; Other Names: traditional rehabilitation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive-Motor Functional Improvement Score	The "Cognitive-Motor Functional Improvement Score" is a composite index designed to assess the enhancement of cognitive and motor functions in study participants. This score takes into account various clinical and psychometric measurements, including parameters such as the Glasgow Coma Scale (GCS), the Glasgow Outcome Scale (GOS), the Level of Cognitive Functioning (LCF), the Coma Recovery Scale-Revised (CRS-R), the Disability Rating Scale (DRS), and the Functional Communication Scale (FCS). The score reflects the progression in cognitive and motor abilities of patients before, during, and after the treatment, providing a comprehensive measure of the success of the rehabilitation intervention.	clinical and psychometric scales will be administered to patients before starting sensory stimulation treatment (time T0), at the end of the stimulation cycle after 4 weeks (time T1), and one month after T1 (follow-up - Time T2).
Examine Short and Long-Term Efficacy	Examine the correlation between neurophysiological and clinical-psychometric parameters to monitor the long-term cognitive-motor effects of advanced multisensory training in individuals with disorders of consciousness, identifying potential predictive indices of recovery. Assessment Method: Clinical evaluations and psychometric tests focusing on cognitive-motor, neurophysiological, and metabolic-nutritional outcomes. Timing: Short-term assessments post-training (T1) and long-term follow-up one month after treatment completion (T2).	clinical and psychometric scales will be administered to patients before starting sensory stimulation treatment (time T0), at the end of the stimulation cycle after 4 weeks (time T1), and one month after T1 (follow-up - Time T2).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study Neurophysiological and Clinical Correlations	The comprehensive evaluation includes continuous clinical monitoring, electroencephalographic (EEG) assessments, and metabolic-nutritional evaluations. The goal is to establish meaningful correlations contributing to predictive indices for long-term cognitive-motor recovery in individuals with consciousness disorders. Evaluation: Clinical Monitoring: Continuous assessment of clinical and psychometric parameters. Electroencephalographic (EEG) Assessments: Recording and analysis of EEG data to monitor neurophysiological responses. Timing: Pre-treatment (T0): Baseline assessment before the commencement of advanced multisensory training. Post-treatment (T1): Evaluation immediately after the completion of the training program. Follow-up (T2): Long-term assessment one month after the conclusion of the treatment to gauge sustained effects and correlations.	clinical and psychometric scales will be administered to patients before starting sensory stimulation treatment (time T0), at the end of the stimulation cycle after 4 weeks (time T1), and one month after T1 (follow-up - Time T2).
Explore the Role of Metabolic-Nutritional Status	This outcome measure investigates the influence of metabolic-nutritional status on cognitive-motor recovery in patients with consciousness disorders. Through a specialized early assessment, it aims to deepen our understanding of how factors such as BMI, creatinine/height, albumin, total proteins, and lymphocyte count contribute to the overall recovery process. The study seeks to unravel the intricate interplay between metabolic-nutritional health and cognitive-motor outcomes in individuals undergoing advanced multisensory training, providing valuable insights for tailored interventions.	clinical and psychometric scales will be administered to patients before starting sensory stimulation treatment (time T0), at the end of the stimulation cycle after 4 weeks (time T1), and one month after T1 (follow-up - Time T2).

Collaborators and Investigators

• Sponsor: IRCCS Centro Neurolesi Bonino Pulejo
• Investigators: Principal Investigator: Maria Grazia Maggio, IRCCS Centro Neurolesi Bonino Pulejo

Publications and helpful links

General Publications

• Sergent C, Faugeras F, Rohaut B, Perrin F, Valente M, Tallon-Baudry C, Cohen L, Naccache L. Multidimensional cognitive evaluation of patients with disorders of consciousness using EEG: A proof of concept study. Neuroimage Clin. 2016 Dec 10;13:455-469. doi: 10.1016/j.nicl.2016.12.004. eCollection 2017.
• Padilla R, Domina A. Effectiveness of Sensory Stimulation to Improve Arousal and Alertness of People in a Coma or Persistent Vegetative State After Traumatic Brain Injury: A Systematic Review. Am J Occup Ther. 2016 May-Jun;70(3):7003180030p1-8. doi: 10.5014/ajot.2016.021022.
• Lombardi F, Taricco M, De Tanti A, Telaro E, Liberati A. Sensory stimulation for brain injured individuals in coma or vegetative state. Cochrane Database Syst Rev. 2002;2002(2):CD001427. doi: 10.1002/14651858.CD001427.
• Keller I, Hulsdunk A, Muller F. The influence of acoustic and tactile stimulation on vegetative parameters and EEG in persistent vegetative state. Funct Neurol. 2007 Jul-Sep;22(3):159-63.

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2023
• Primary Completion (Actual): December 14, 2024
• Study Completion (Actual): March 30, 2025

Study Registration Dates

• First Submitted: December 15, 2023
• First Submitted That Met QC Criteria: January 2, 2024
• First Posted (Actual): January 12, 2024

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 2, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Disorders of Consciousness; Acquired Brain Injury; Multisensory Stimulation; Cognitive-Motor rehabilitation; Metabolic-Nutritional Status
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Wounds and Injuries; Neurobehavioral Manifestations; Neurocognitive Disorders; Craniocerebral Trauma; Trauma, Nervous System; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Brain Injuries; Consciousness Disorders
• Other Study ID Numbers: 02/2023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We plan to make individual participant data (IPD) available to other researchers. This means that we intend to publish the databases, allowing access for other researchers to utilize the individualized data collected from each participant in our study. By doing so, we aim to contribute to the broader scientific community, fostering collaboration and enabling further exploration and analysis of the information gathered during our research.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No