Assessment of Noninvasive Neuromodulation in a Group of Traumatic Brain Injured Patients and Healthy Volunteers

Effects of Neurobiological Therapy With Asymmetric Radio-electric Conveyer (REAC) in Diffuse Axonal Injury: a Randomized Controlled Trial.

Background: Severe traumatic brain injury, particularly diffuse axonal injury (DAI), often leads to lasting neurological issues. Cerebral dysfunction in DAI can be evaluated by monitoring cerebral electrical activity (CEA) through EEG. The radio electric asymmetric conveyer (REAC) is a noninvasive method designed to rebalance cellular polarity via endogenous bioelectric fields and modulate CEA. This technique may alter CEA, which can be detected using quantitative EEG (qEEG).

Objective: To assess qEEG changes following DAI and brain wave alterations after a REAC protocol in this group.

Methods: In this prospective, randomized, double-blind clinical trial, DAI patients will be assigned to active or sham groups for 19 sessions of either true or sham REAC following ICU discharge. Interventions include one Neuro Postural Optimization session and 18 NPPO-BWO-G sessions (up to four per day). The main outcome is to evaluate changes in qEEG patterns through population brain electrical mapping after REAC therapies.

Study Overview

• Status: Recruiting
• Conditions: Traumatic Brain Injury
• Intervention / Treatment: Device: Subjects in the intervention group receive low-frequency radioelectric therapy; Device: Sham, the device simulates a therapy session

Detailed Description

Traumatic brain injury (TBI) is a leading cause of death and disability globally, significantly affecting the quality of life for patients and caregivers.

In the United States, traumatic brain injury is the leading cause of death for people aged 1 to 45 and a major risk factor for morbidity and mortality in politrauma cases.

Although epidemiological data in Brazil are limited, studies indicate that TBI is a significant public health issue, primarily impacting the country's young and economically active population.

Automobile accidents and falls are primary causes of traumatic brain injury, with incidence rates highest among young adults (20 to 29 years) and individuals over 80 years old.

TBI is a highly heterogeneous condition, with multiple classification systems that emphasize distinct aspects such as the underlying mechanism of injury, clinical severity, radiological characteristics, and pathophysiological processes. These classifications play an important role in standardizing data collection, identifying prognostic factors, and informing the selection of appropriate therapeutic approaches tailored to individual cases.

From a pathophysiological perspective, traumatic brain injury (TBI) causes damage through primary lesions-direct energy transfer to the brain at trauma-and secondary effects, which involve cellular and molecular changes occurring for hours to weeks post-injury.

Diffuse axonal injury (DAI) is a type of lesion in TBI that leads to significant brain dysfunction and affects roughly 40% of patients, making it a leading cause of neurological problems in survivors.

Clinically, it is defined as a coma lasting more than 6 hours after TBI, excluding cases caused by ischemic brain injury or intracranial masses.

Detecting this condition during routine exams in TBI patients can be challenging, as DAI-related abnormalities are often missed by standard CT or MRI scans and may require advanced imaging techniques to identify structural changes in the central nervous system.

From a neurological perspective, TBI can result in a wide range of cognitive, behavioral, and sensory-motor changes that may affect the patient's quality of life. Cognition encompasses the processes involved in acquiring knowledge and includes factors such as thought, language, memory, reasoning, and task execution, which are considered important for intellectual development.

Although TBI is strongly linked to cognitive dysfunction, effective treatment remains difficult. While cognitive rehabilitation therapies have shown benefits in some studies, results are inconsistent.

Drug therapies for post-TBI cognitive disorders have proven ineffective. The limited effectiveness of conventional cognitive rehabilitation in DAI patients has led to the exploration of new therapies. Neuromodulation techniques, both invasive and noninvasive, offer promising options by targeting specific brain regions to alter activity and support recovery.

Radio-electric asymmetric conveyer (REAC) technology is a noninvasive technique that was first described by Rinaldi and Fontani. REAC neurobiological modulation with specific protocols such as neuro-postural-optimization (NPO) and neuro-psycho-physical-optimization - brain wave optimization-G (NPPO-BWO-G) is a safe, established technique with proven therapeutic benefits for various neurological and psychiatric disorders.

Given the significant brain damage and multiple disabling neurological sequelae, in severe TBI patients, combined with the limited efficacy of conventional pharmacological and cognitive rehabilitation interventions, REAC may be a promising therapeutic approach for affected patients. We will conduct a randomized clinical trial to assess REAC's effects in patients with DAI.

GOALS Primary Endpoint

• To evaluate the qEEG changes in patients with subacute/chronic DAI, following REAC neuromodulation.

Secondary Endpoint

• To evaluate the qEEG changes in adults free of neurological conditions, following REAC neuromodulation.
• To evaluate cognitive and humor changes in adults free of neurological conditions, following REAC neuromodulation.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sérgio Brasil, MD. PhD.; Phone Number: +5511981210990; Email: sbrasil@alumni.usp.br
• Study Contact Backup: Name: Alessandra C Renck, MD. PhD.; Phone Number: +5511981211114; Email: alerenck@alumni.usp.br

Study Locations

• Brazil
  • São Paulo
    • São Paulo, São Paulo, Brazil, 05.403-905
      • Recruiting
      • Hospital das Clínicas da FM-USP
      • Contact: Wellingson Paiva, MD. PhD.; Phone Number: +5511975992245; Email: wellingsonpaiva@yahoo.com.br

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• DAI diagnostic and consent for participation with the next of kin for each eligible patient

Exclusion Criteria:

• Open TBI
• History of chronic neurological conditions

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ACTIVE; Subjects undergoing active therapy	Device: Subjects in the intervention group receive low-frequency radioelectric therapy; The intervention is based on two treatment protocols, the neuro-postural optimization in single aplication and brain-waves optimization in 18 sessions. This protocol is exclusive for the present study.
Sham Comparator: SHAM; Subjects receiving sham therapy	Device: Sham, the device simulates a therapy session; The device simulates a therapy session

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Observe if there are significant changes in the electroencephalographic pattern, compared between the groups.	Six months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Observe if there are significant clinical improvement determined by the modified Rankin scale between the groups.	The modified Rankin scale has scores from 0 to 5, where 5 is the worst outcome (severe disability and remaining in bed), whereas 0 is the absence of any limitation (total recovery).	six months
Observe if there are significant clinical improvement determined by the Glasgow outcome scale between the groups.	The extended Glasgow outcome scale (GOSE) has scores from 1 to 8, considering upper limbs and/or lower limbs disability. 1 is the worst outcome (death), whereas 8 is the total recovery of upper limbs.	Six months

Collaborators and Investigators

• Sponsor: University of Sao Paulo
• Collaborators: Istituto Rinaldi Fontana

Publications and helpful links

General Publications

• Hyder AA, Wunderlich CA, Puvanachandra P, Gururaj G, Kobusingye OC. The impact of traumatic brain injuries: a global perspective. NeuroRehabilitation. 2007;22(5):341-53.
• Rinaldi S, Mura M, Castagna A, Fontani V. (2014) Long-lasting changes in brain activation induced by a single REAC technology pulse in Wi-Fi bands. Randomized double-blind fMRI qualitative study. Sci Rep 4:5668. https://doi.org/10.1038/srep05668
• Castagna A, Rinaldi S, Fontani V, Aravagli L, Mannu P, Margotti ML. (2010) Does osteoarthritis of the knee also have a psychogenic component? Psycho-emotional treatment with a radio-electric device vs. intra-articular injection of sodium hyaluronate: an open-label, naturalistic study. Acupunct Electrother Res 35:1-16. https://doi.org/10.3727/036012910803860968
• Li S, Zaninotto AL, Neville IS, Paiva WS, Nunn D, Fregni F. (2015) Clinical utility of brain stimulation modalities following traumatic brain injury: current evidence. Neuropsychiatr Dis Treat 11:1573-1586. https://doi.org/10.2147/NDT.S65816
• Zaninotto AL, Vicentini JE, Solla DJ, Silva TT, Guirado VM, Feltrin F, de Lucia MC, Teixeira MJ, Paiva WS. (2017) Visuospatial memory improvement in patients with diffuse axonal injury (DAI): a 1-year follow-up study. Acta Neuropsychiatr 29:35-42. https://doi.org/10.1017/neu.2016.29
• Rinaldi C, Landre CB, Volpe MI, Goncalves RG, Nunes LDS, Darienso D, Cruz AV, Oliveira JD, Rinaldi S, Fontani V, Barcessat AR. Improving Functional Capacity and Quality of Life in Parkinson's Disease Patients through REAC Neuromodulation Treatments for Mood and Behavioral Disorders. J Pers Med. 2023 Jun 1;13(6):937. doi: 10.3390/jpm13060937.
• Goncalves de Oliveira Cruz AV, Goes Goncalves R, Nunes L, Douglas Quaresma de Oliveira J, Lima Monteiro ES, Soares Eneias I, Guilherme Lima TC, Duarte Ferreira L, Souza Neri E, da Cunha Pena JL, Celis de Cardenas AM, Cortes Volpe MI, Filgueiras de Assis Melo MV, Rinaldi A, Pinheiro Barcessat AR. (2022) Neuro Postural Optimization Neuromodulation Treatment of Radio Electric Asymmetric Conveyer Technology on Stress and Quality of Life in Institutionalized Children in a Capital City of the Brazilian Amazon. Cureus 14:e26550. https://doi.org/10.7759/cureus.26550
• Pinheiro Barcessat AR, Nolli Bittencourt M, Duarte Ferreira L, de Souza Neri E, Coelho Pereira JA, Bechelli F, Rinaldi A. (2020) REAC Cervicobrachial Neuromodulation Treatment of Depression, Anxiety, and Stress During the COVID-19 Pandemic. Psychol Res Behav Manag 13:929-937. https://doi.org/10.2147/PRBM.S275730
• Rinaldi A, Rinaldi C, Coelho Pereira JA, Lotti Margotti M, Bittencourt MN, Barcessat ARP, Fontani V, Rinaldi S. (2019) Radio electric asymmetric conveyer neuromodulation in depression, anxiety, and stress. Neuropsychiatr Dis Treat 15:469-480. https://doi.org/10.2147/NDT.S195466
• Gennarelli TA, Spielman GM, Langfitt TW, Gildenberg PL, Harrington T, Jane JA, Marshall LF, Miller JD, Pitts LH. (1982) Influence of the type of intracranial lesion on outcome from severe head injury. J Neurosurg 56:26-32. https://doi.org/10.3171/jns.1982.56.1.0026
• de Almeida CE, de Sousa Filho JL, Dourado JC, Gontijo PA, Dellaretti MA, Costa BS. (2016) Traumatic Brain Injury Epidemiology in Brazil. World Neurosurg 87:540-547. https://doi.org/10.1016/j.wneu.2015.10.020

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: September 28, 2025
• First Submitted That Met QC Criteria: January 19, 2026
• First Posted (Actual): January 28, 2026

Study Record Updates

• Last Update Posted (Actual): January 28, 2026
• Last Update Submitted That Met QC Criteria: January 19, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: NEUROMODULATION; TRAUMATIC BRAIN INJURY; DIFFUSE AXONAL INJURY; RADIOELECTRIC ASSIMETRIC CONVEYER
• Additional Relevant MeSH Terms: Brain Injuries, Diffuse; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Brain Injuries, Traumatic; Diffuse Axonal Injury
• Other Study ID Numbers: 84791824.8.0000.0068

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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