GRAViceptive NEGlect Treatment in Acute Stroke Using Targeted Cranial ELECTrotherapy (GravNegElect)

Graviceptive Neglect After Stroke: Clinical, Neuroanatomical and Physiological Effects of Focal Neuromodulation

We aim to determine if targeted high-definition transcranial direct current stimulation (HD-tDCS) can safely correct errors in visual verticality perception in patients after stroke affecting either hemisphere.

Study Overview

• Status: Recruiting
• Conditions: Stroke
• Intervention / Treatment: Device: Active: High-Definition transcranial Direct Current Stimulation (HD-tDCS); Device: Sham: High-Definition transcranial Direct Current Stimulation (HD-tDCS)

Detailed Description

This study explores a new approach to treat graviceptive neglect, a condition that affects balance and perception of uprightness, using a non-invasive brain stimulation technique called HD-tDCS (high-definition transcranial direct current stimulation). Using a phase I/II randomized sham-controlled double-blind parallel clinical trial design, we aim to analyze if HD-tDCS can safely help correct abnormal visual verticality perception in 28 people after stroke. We will also investigate the effects of our protocol on cerebrovascular response using transcranial Doppler and cortical activity using EEG. Neuroanatomical characteristics will be analyzed to establish the relationship between verticality perception error and the extent of temporo-parietal junction (TPJ) damage and, more broadly, the putative VV structural brain Network (VVN). Each participant will receive six HD-tDCS sessions of 2mA for 20 minutes in a central cathode montage applied over the contralesional TPJ. Patients will be randomized into two groups, with 50% receiving active stimulation and 50% receiving sham stimulation. The sham stimulation condition will consist of the same electrode placement, with a 2mA ramp-up over 30 seconds, followed by a 30-second ramp-down. Both groups will undergo 6 sessions, three times a day, for 2 days. The follow-up assessment will be performed 1 month after stimulation.

• Study Type: Interventional
• Enrollment (Estimated): 28
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Taiza G. S. Edwards, PhD; Phone Number: +55-16-33153379; Email: taiza@fmrp.usp.br
• Study Contact Backup: Name: Lizanilda Albuquerque, BSc; Phone Number: +55-16-36021202; Email: lizanilda@usp.br

Study Locations

• Brazil
  • SP
    • Ribeirão Preto, SP, Brazil, 14015160
      • Recruiting
      • Ribeirão Preto Medical School, University of São Paulo
      • Contact: Taiza Edwards, PhD; Phone Number: +55-16-36021202; Email: taiza@fmrp.usp.br
      • Contact: Post-Graduate Program in Neurology Ribeirão Preto Medical School, University of São Paulo, Assistant; Phone Number: +55-16-33153379; Email: ppg.fmrpncc@usp.br
      • Contact: Taiza Edwards, PhD
    • Ribeirão Preto, SP, Brazil, 14049-900
      • Not yet recruiting
      • University of São Paulo, Ribeirão Preto Medical School

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Supratentorial ischemic stroke diagnosed by neuroimaging and clinical analysis;
• Clinically stable (stable vital signs for 24 hours; no chest pain in the last 24 hours; no significant arrhythmia; no evidence of deep vein thrombosis);
• Normal or corrected-to-normal vision;
• No previous experience with HD-tDCS;
• Ability to provide informed consent (patient or legal representative);
• Ability to comply with the intervention and assessment schedule of the protocol.
• Presence of visual verticality misperception.

Exclusion Criteria:

• Migraine;
• Pregnancy;
• Pacemakers;
• Seizures;
• Claustrophobia;
• Transient ischemic attack;
• Other neurological disorders;
• Psychiatric disorders;
• Sensitive scalp or prior brain surgery;
• Diagnosis of severe carotid atherosclerotic disease (stenosis ≥ 70%);
• Presence of metal implants, cardiac pacemakers, or claustrophobia;
• Diagnosis of COVID-19 or other infectious disease that requires isolation;
• Uncontrolled medical problems, such as terminal cancer or kidney disease.
• Left-handed or mixed-handed individuals as determined using the Edinburgh Handedness Inventory (Appendix 10);
• Peripheral vestibular deficits observed using neuro-otological screening tests when the participant's clinical condition allows (head shake test, head thrust test, Dix-Hallpike, and Pagnini-McClure);
• Prior musculoskeletal disorders affecting alignment and postural balance (e.g., moderate to severe scoliosis; torticollis);
• Cognitive dysfunction outside normal limits on the Mini-Mental State Examination (score below 23);
• Global or Wernicke's aphasia;

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
Experimental: Active HD-tDCS; Participants will receive six sessions of 2mA active HD-tDCS cathode center over the contralesional TPJ for 20 minutes, 3 times daily for 2 days with session intervals greater than 3 hours.	Device: Active: High-Definition transcranial Direct Current Stimulation (HD-tDCS); Active high-definition transcranial direct current stimulation (HD-tDCS) will be delivered by a low-intensity direct current stimulator (Soterix Medical) using a 3x1 ring configuration with a central cathode over the contralesional temporo-parietal junction. During the stimulation, participants will perform tasks to stimulate correct visual verticality perception. Six active HD-tDCS sessions of 2mA for 20 minutes HD-tDCS, 3 times daily for 2 days with session intervals greater than 3 hours.
Sham Comparator: Sham HD-tDCS; Participants will receive six sessions of 2mA sham HD-tDCS cathode center over the contralesional TPJ for 20 minutes, 3 times daily for 2 days with session intervals greater than 3 hours.	Device: Sham: High-Definition transcranial Direct Current Stimulation (HD-tDCS); Six sessions (3 times daily for 2 days) of 2mA sham HD-tDCS cathode center over the contralesional TPJ for 20min. Direct current (DC) will be generated by a low-intensity direct current stimulator (Soterix Medical) and then split into the 3 high-density Ag/AgCl sintered ring electrodes. The sham stimulation condition will consist of the same positioning of the electrodes as the active condition, with a ramp-up to 2mA over 30 seconds and a subsequent ramp-down of 30 seconds.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Verticality Perception (VV; visual graviceptive neglect)	Change in VV: assessment using the bucket method.	From baseline (before the first session) to 1 day post-intervention protocol (after six HDtDCS sessions).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Verticality Perception (VV; visual graviceptive neglect)	Change in VV: assessment using the bucket method.	From baseline (before the first session) to 30±5 days post-intervention protocol (after six HDtDCS sessions).
Ocular torsion	Change in ocular torsion: assessment using fundus photography (Phelcom; Eyer 1 device)	From baseline (before the first session) to 1 day post-intervention protocol (after six HDtDCS sessions).
Ocular torsion	Change in ocular torsion: assessment using fundus photography (Phelcom; Eyer 1 device)	From baseline (before the first session) to 30±5 days post-intervention protocol (after six HDtDCS sessions).
Electroencephalography	Electroencephalography measurements focusing on resting state networks related to visual verticality perception.	From baseline (before the first session) to 1 day post-intervention protocol (after six HDtDCS sessions).
Electroencephalography	Electroencephalography measurements focusing on resting state networks related to visual verticality perception.	From baseline (before the first session) to 30±5 days post-intervention protocol (after six HDtDCS sessions).
Cerebrovascular reactivity	Transcranial Doppler Ultrasonography (TCD; Viasonix Dolphin/XF Robot) will be employed to measure cerebral blood flow velocity in the middle cerebral arteries while the participant performs the breath-holding maneuver.	From baseline (before the first session) to 1 day post-intervention protocol (after six HDtDCS sessions).
Cerebrovascular reactivity	Transcranial Doppler Ultrasonography (TCD; Viasonix Dolphin/XF Robot) will be employed to measure cerebral blood flow velocity in the middle cerebral arteries while the participant performs the breath-holding maneuver.	From baseline (before the first session) to 30±5 days post-intervention protocol (after six HDtDCS sessions).
Spatial neglect	Spatial neglect will be assessed using the conventional Behavior Inattention Test (BIT), which consists of 6 items: 1) line crossing; 2) letter cancellation; 3) star cancellation; 4) figure and shape copying; 5) line bisection; and 6) representational drawing.	From baseline (before the first session) to 1 day post-intervention protocol (after six HDtDCS sessions).
Spatial neglect	Spatial neglect will be assessed using the conventional Behavior Inattention Test (BIT), which consists of 6 items: 1) line crossing; 2) letter cancellation; 3) star cancellation; 4) figure and shape copying; 5) line bisection; and 6) representational drawing.	From baseline (before the first session) to 30±5 days post-intervention protocol (after six HDtDCS sessions).

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain magnetic resonance imaging (MRI)	The structural integrity of the visual verticality network will be evaluated using diffusion MRI.	Up to 15 days post stroke.

Collaborators and Investigators

• Sponsor: University of Sao Paulo
• Collaborators: Thomas Jefferson University; The São Paulo Research Foundation (FAPESP); Viasonix; Phelcom; FBX Medical
• Investigators: Principal Investigator: Taiza Edwards, PhD, Ribeirão Preto Medical School, University of São Paulo

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2025
• Primary Completion (Estimated): January 15, 2026
• Study Completion (Estimated): January 15, 2026

Study Registration Dates

• First Submitted: December 18, 2024
• First Submitted That Met QC Criteria: December 18, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 29, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Stroke; Neuroimaging; Transcranial doppler; Electroencephalography; Non-invasive Brain Stimulation; HD-tDCS; Graviceptive Neglect; Verticality Perception
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke
• Other Study ID Numbers: 74877723.4.0000.5440; 2023/03252-2 (Other Grant/Funding Number: The São Paulo Research Foundation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes