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

Official title

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

Overview

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.

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.

Interventions

• 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.
• Device Sham, the device simulates a therapy session
  The device simulates a therapy session

Primary outcome measures

• Observe if there are significant changes in the electroencephalographic pattern, compared between the groups. [Time frame: Six months]

Secondary outcome measures (2)

• Observe if there are significant clinical improvement determined by the modified Rankin scale between the groups. [Time frame: six months]
• Observe if there are significant clinical improvement determined by the Glasgow outcome scale between the groups. [Time frame: Six months]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Brazil · 1 center

• Hospital das Clínicas da FM-USP — São Paulo

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. PMID 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. PMID 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. PMID 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. PMID 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. PMID 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 PMID 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. PMID 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. PMID 30858704

Identifiers

NCT: NCT07373366 · 84791824.8.0000.0068

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗