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Traumatic Brain InjuryPhase 2NCT07373366

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

A Phase 2 study testing Subjects in the intervention group receive low-frequency radioelectric therapy in people with Traumatic Brain Injury, run by University of Sao Paulo at 1 site in Brazil.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

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. Read more about this study

Who is it for?
Any ageHealthy volunteers can take part
Conditions the study is for
Traumatic Brain Injury
What is being tested?
Subjects in the intervention group receive low-frequency radioelectric therapy
Type of treatment
Medical device
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
60 participants
Where
1 siteBrazil
Study dates
1 Apr 2025to May 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult, Older adult

Who may be able to join

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

Who cannot join

  • Open TBI
  • History of chronic neurological conditions

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Sérgio Brasil, MD. PhD. contact

+5511981210990

sbrasil@alumni.usp.br

Alessandra C Renck, MD. PhD. contact

+5511981211114

alerenck@alumni.usp.br

Brazil1 site, 1 recruiting
  • Hospital das Clínicas da FM-USP

    São Paulo, São Paulo, 05.403-905

    Wellingson Paiva, MD. PhD., +5511975992245, wellingsonpaiva@yahoo.com.br

    Recruiting

Other trials in Brazil

About this study

Official title: 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.

Read the 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.
Being tested
Subjects in the intervention group receive low-frequency radioelectric therapy, Sham, the device simulates a therapy session
Keywords
TRAUMATIC BRAIN INJURY, DIFFUSE AXONAL INJURY, NEUROMODULATION, RADIOELECTRIC ASSIMETRIC CONVEYER
Medical subject headings
Brain Injuries, Traumatic, Diffuse Axonal Injury

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Subjects in the intervention group receive low-frequency radioelectric therapyDevice

    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, the device simulates a therapy sessionDevice

    The device simulates a therapy session

Study groups in NCT07373366
Study groupRoleWhat they receive
ACTIVEActive comparatorSubjects undergoing active therapy
Receives: Device: Subjects in the intervention group receive low-frequency radioelectric therapy
SHAMSham comparatorSubjects receiving sham therapy
Receives: Device: Sham, the device simulates a therapy session

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Observe if there are significant changes in the electroencephalographic pattern, compared between the groups.

    Measured: Six months

Secondary outcomes (2)
  1. 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).

    Measured: six months

  2. 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.

    Measured: Six months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jan 2026
  2. Study start1 Apr 2025
  3. Primary completionDec 2026 (estimated)
  4. Study completionMay 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Patient selection Medical record, radiology, participation consent Step 1 (pre-intervention) qEEG, TCD and brain4care up to 3 days before the start of REAC sessions Step 2 (intervention) NPO neuromodulation (single session) Step 3 (intervention) NPPO-GW neuromodulation (18 sessions) Step 4 (post-intervention) qEEG, TCD and brain4care up to 3 days after the end of REAC sessions Follow-up discharge, 3m and 6m - mRankin, GOSE, DASS 21
Masking
Triple blind
Who is masked
Participant, Care provider, Outcomes assessor
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07373366
Sponsor's protocol ID
84791824.8.0000.0068
Status last verified
Jan 2026
First submitted
28 Sep 2025
Last updated
28 Jan 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Rinaldi S, Mura M, Castagna A, Fontani V. 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. 2014 Jul 11;4:5668. doi: 10.1038/srep05668.

    PubMed 25011544
  • Castagna A, Rinaldi S, Fontani V, Aravagli L, Mannu P, Margotti ML. 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. 2010;35(1-2):1-16. doi: 10.3727/036012910803860968.

    PubMed 20578643
  • Li S, Zaninotto AL, Neville IS, Paiva WS, Nunn D, Fregni F. Clinical utility of brain stimulation modalities following traumatic brain injury: current evidence. Neuropsychiatr Dis Treat. 2015 Jun 30;11:1573-86. doi: 10.2147/NDT.S65816. eCollection 2015.

    PubMed 26170670
  • Zaninotto AL, Vicentini JE, Solla DJ, Silva TT, Guirado VM, Feltrin F, de Lucia MC, Teixeira MJ, Paiva WS. Visuospatial memory improvement in patients with diffuse axonal injury (DAI): a 1-year follow-up study. Acta Neuropsychiatr. 2017 Feb;29(1):35-42. doi: 10.1017/neu.2016.29. Epub 2016 Oct 11.

    PubMed 27725006
  • 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.

    PubMed 37373926
  • 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. 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. 2022 Jul 4;14(7):e26550. doi: 10.7759/cureus.26550. eCollection 2022 Jul.

    PubMed 35815301
  • Pinheiro Barcessat AR, Nolli Bittencourt M, Duarte Ferreira L, de Souza Neri E, Coelho Pereira JA, Bechelli F, Rinaldi A. REAC Cervicobrachial Neuromodulation Treatment of Depression, Anxiety, and Stress During the COVID-19 Pandemic. Psychol Res Behav Manag. 2020 Nov 9;13:929-937. doi: 10.2147/PRBM.S275730. eCollection 2020.

    PubMed 33204186
  • Rinaldi A, Rinaldi C, Coelho Pereira JA, Lotti Margotti M, Bittencourt MN, Barcessat ARP, Fontani V, Rinaldi S. Radio electric asymmetric conveyer neuromodulation in depression, anxiety, and stress. Neuropsychiatr Dis Treat. 2019 Feb 13;15:469-480. doi: 10.2147/NDT.S195466. eCollection 2019.

    PubMed 30858704
  • Gennarelli TA, Spielman GM, Langfitt TW, Gildenberg PL, Harrington T, Jane JA, Marshall LF, Miller JD, Pitts LH. Influence of the type of intracranial lesion on outcome from severe head injury. J Neurosurg. 1982 Jan;56(1):26-32. doi: 10.3171/jns.1982.56.1.0026. No abstract available.

    PubMed 7054419
  • de Almeida CE, de Sousa Filho JL, Dourado JC, Gontijo PA, Dellaretti MA, Costa BS. Traumatic Brain Injury Epidemiology in Brazil. World Neurosurg. 2016 Mar;87:540-7. doi: 10.1016/j.wneu.2015.10.020. Epub 2015 Oct 17.

    PubMed 26485419
  • 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.

    PubMed 18162698

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Subjects in the intervention group receive low-frequency radioelectric therapy in people with Traumatic Brain Injury, run by University of Sao Paulo at 1 site in Brazil.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 28 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Sérgio Brasil, MD. PhD. (+5511981210990, sbrasil@alumni.usp.br), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Observe if there are significant changes in the electroencephalographic pattern, compared between the groups. (time frame: Six months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07373366, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2026.

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