Ignite Creation Date:
2026-03-26 @ 3:15 PM
Ignite Modification Date:
2026-03-26 @ 3:15 PM
Study NCT ID:
NCT07373366
Status:
RECRUITING
Last Update Posted:
2026-01-28
First Post:
2025-09-28
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Assessment of Noninvasive Neuromodulation in a Group of Traumatic Brain Injured Patients and Healthy Volunteers
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000070642', 'term': 'Brain Injuries, Traumatic'}, {'id': 'D020833', 'term': 'Diffuse Axonal Injury'}], 'ancestors': [{'id': 'D001930', 'term': 'Brain Injuries'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D006259', 'term': 'Craniocerebral Trauma'}, {'id': 'D020196', 'term': 'Trauma, Nervous System'}, {'id': 'D014947', 'term': 'Wounds and Injuries'}, {'id': 'D000070625', 'term': 'Brain Injuries, Diffuse'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2025-10-15', 'size': 436969, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_000.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2026-01-19T18:24', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Patient selection Medical record, radiology, participation consent\n\nStep 1 (pre-intervention) qEEG, TCD and brain4care up to 3 days before the start of REAC sessions\n\nStep 2 (intervention) NPO neuromodulation (single session)\n\nStep 3 (intervention) NPPO-GW neuromodulation (18 sessions)\n\nStep 4 (post-intervention) qEEG, TCD and brain4care up to 3 days after the end of REAC sessions\n\nFollow-up discharge, 3m and 6m - mRankin, GOSE, DASS 21'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 60}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2025-04-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2026-01', 'completionDateStruct': {'date': '2027-05', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2026-01-19', 'studyFirstSubmitDate': '2025-09-28', 'studyFirstSubmitQcDate': '2026-01-19', 'lastUpdatePostDateStruct': {'date': '2026-01-28', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2026-01-28', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2026-12', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Observe if there are significant changes in the electroencephalographic pattern, compared between the groups.', 'timeFrame': 'Six months'}], 'secondaryOutcomes': [{'measure': 'Observe if there are significant clinical improvement determined by the modified Rankin scale between the groups.', 'timeFrame': 'six months', 'description': '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).'}, {'measure': 'Observe if there are significant clinical improvement determined by the Glasgow outcome scale between the groups.', 'timeFrame': 'Six months', 'description': '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.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['TRAUMATIC BRAIN INJURY', 'DIFFUSE AXONAL INJURY', 'NEUROMODULATION', 'RADIOELECTRIC ASSIMETRIC CONVEYER'], 'conditions': ['Traumatic Brain Injury']}, 'referencesModule': {'references': [{'type': 'BACKGROUND', 'citation': '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'}, {'type': 'BACKGROUND', 'citation': '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'}, {'type': 'BACKGROUND', 'citation': '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'}, {'type': 'BACKGROUND', 'citation': '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'}, {'pmid': '37373926', 'type': 'BACKGROUND', 'citation': "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."}, {'type': 'BACKGROUND', 'citation': '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'}, {'type': 'BACKGROUND', 'citation': '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'}, {'type': 'BACKGROUND', 'citation': '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'}, {'type': 'BACKGROUND', 'citation': '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'}, {'type': 'BACKGROUND', 'citation': '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'}, {'pmid': '18162698', 'type': 'BACKGROUND', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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).\n\nObjective: To assess qEEG changes following DAI and brain wave alterations after a REAC protocol in this group.\n\nMethods: 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.', 'detailedDescription': "Traumatic brain injury (TBI) is a leading cause of death and disability globally, significantly affecting the quality of life for patients and caregivers.\n\nIn 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.\n\nAlthough 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.\n\nAutomobile 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.\n\nTBI 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.\n\nFrom 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.\n\nDiffuse 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.\n\nClinically, it is defined as a coma lasting more than 6 hours after TBI, excluding cases caused by ischemic brain injury or intracranial masses.\n\nDetecting 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.\n\nFrom 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.\n\nAlthough TBI is strongly linked to cognitive dysfunction, effective treatment remains difficult. While cognitive rehabilitation therapies have shown benefits in some studies, results are inconsistent.\n\nDrug 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.\n\nRadio-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.\n\nGiven 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.\n\nGOALS Primary Endpoint\n\n• To evaluate the qEEG changes in patients with subacute/chronic DAI, following REAC neuromodulation.\n\nSecondary Endpoint\n\n* To evaluate the qEEG changes in adults free of neurological conditions, following REAC neuromodulation.\n* To evaluate cognitive and humor changes in adults free of neurological conditions, following REAC neuromodulation."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* DAI diagnostic and consent for participation with the next of kin for each eligible patient\n\nExclusion Criteria:\n\n* Open TBI\n* History of chronic neurological conditions'}, 'identificationModule': {'nctId': 'NCT07373366', 'briefTitle': 'Assessment of Noninvasive Neuromodulation in a Group of Traumatic Brain Injured Patients and Healthy Volunteers', 'organization': {'class': 'OTHER', 'fullName': 'University of Sao Paulo'}, 'officialTitle': 'Effects of Neurobiological Therapy With Asymmetric Radio-electric Conveyer (REAC) in Diffuse Axonal Injury: a Randomized Controlled Trial.', 'orgStudyIdInfo': {'id': '84791824.8.0000.0068'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'ACTIVE', 'description': 'Subjects undergoing active therapy', 'interventionNames': ['Device: Subjects in the intervention group receive low-frequency radioelectric therapy']}, {'type': 'SHAM_COMPARATOR', 'label': 'SHAM', 'description': 'Subjects receiving sham therapy', 'interventionNames': ['Device: Sham, the device simulates a therapy session']}], 'interventions': [{'name': 'Subjects in the intervention group receive low-frequency radioelectric therapy', 'type': 'DEVICE', 'description': '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.', 'armGroupLabels': ['ACTIVE']}, {'name': 'Sham, the device simulates a therapy session', 'type': 'DEVICE', 'description': 'The device simulates a therapy session', 'armGroupLabels': ['SHAM']}]}, 'contactsLocationsModule': {'locations': [{'zip': '05.403-905', 'city': 'São Paulo', 'state': 'São Paulo', 'status': 'RECRUITING', 'country': 'Brazil', 'contacts': [{'name': 'Wellingson Paiva, MD. PhD.', 'role': 'CONTACT', 'email': 'wellingsonpaiva@yahoo.com.br', 'phone': '+5511975992245'}], 'facility': 'Hospital das Clínicas da FM-USP', 'geoPoint': {'lat': -23.5475, 'lon': -46.63611}}], 'centralContacts': [{'name': 'Sérgio Brasil, MD. PhD.', 'role': 'CONTACT', 'email': 'sbrasil@alumni.usp.br', 'phone': '+5511981210990'}, {'name': 'Alessandra C Renck, MD. PhD.', 'role': 'CONTACT', 'email': 'alerenck@alumni.usp.br', 'phone': '+5511981211114'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Sao Paulo', 'class': 'OTHER'}, 'collaborators': [{'name': 'Istituto Rinaldi Fontana', 'class': 'UNKNOWN'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'MD. PhD.', 'investigatorFullName': 'Sergio Brasil, MD', 'investigatorAffiliation': 'University of Sao Paulo'}}}}