NCT05833568

Five-day 20-minute 10-Hz tACS in Patients With a Disorder of Consciousness

Double-blind Randomized Controlled Trial of a 10-Hz Transcranial Alternating Current Stimulation to Modulate Brain Activity in Brain-injured Patients With Disorders of Consciousness

• Status: Unknown
• Phase: N/A
• Study type: Interventional
• Enrollment: 138 (estimated)
• Sponsor: Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study first aims to validate the feasibility of a multimodal 5-day 20-minute tACS protocol in subacute brain-injured patients with a disorder of consciousness during their ICU stay, and conduct a clinical pilot study (validation phase). Upon completion of this validation phase and according to obtained results, a randomized clinical trial will be conducted to compare the effects of the 5-day active 10Hz-tACS protocol with a 5-day sham-tACS protocol on brain dynamics modulation. This study will also compare intervention conditions on recovery of consciousness, cognition and function using short-term and long-term measurements.

Detailed description

Background: After a severe brain injury, a significant number of patients remain in a state of altered consciousness and the outcome remains difficult to prognosticate. There is a lack of evidence-based therapeutic interventions available for patients with disorders of consciousness; some evidence has been gathered for non-invasive brain stimulation, but these have targeted chronic patients. The objective of the validation phase will be to evaluate the differential feasibility parameters of conducting a 5-day tACS stimulation protocol in the ICU and the quality of data collection according to the various measurement modalities, to establish requirements to be used in a larger-scale study. This phase will also implicate a clinical pilot to confirm and assess the effect size of the primary outcome and sample size requirements for a clinical trial. Following completion, a clinical trial will be conducted to evaluate short-term and long-term neurophysiological effects of an optimized, multi-session tACS intervention in subacute brain-injured patients on their consciousness and functional recovery (as measured by complementary behavioural/functional scales), related brain oscillations and network dynamics. Validation phase: In addition to conducting the following methods and design protocol, these measures will be acquired during the validation phase to assess the feasibility of this single-site study. Recruitment rate and retention: Estimated number of patients in this condition in this ICU per year, estimated patient survival rates, number of eligible patients over a 12-month recruitment period; percentage of patients recruited, attrition, presence of competitive studies, etiologies and compliance of the families through experimental protocol and longitudinal assessment (12-month period). Site demographics: Personnel's availabilities, Availability/accessibility of study coordinators, technicians, doctors and nurses; competency of the experimental team to conduct the experimental protocol. Site infrastructure: Material storage (biological samples (centrifuge, freezer), Material obtention (Lidocaine obtention and renewal; EEG equipment), Data storage (clinically secure on-site servers). Investigators' team requirements: Personnel requirements and the number of personnel required for the protocol's conductance. Assessing the investigator's readiness in terms of standard care (eligibility decisions according to clinical profiles ), targeted study population and population recruited, and familiarity with the use of tools and technology. Acceptability within the clinical care team's ecosystem: document pitfalls, difficulties and requirements to facilitate the clinical care team's adherence Quality of data collection: quality of EEG signal data in different clinical settings across main acquisition hospital sites; percentage of data acquisition completion; encountered data acquisition obstacles; assessment the estimated acquisition time for each measure and actual measuring times. Methods/design: The investigators will recruit brain-injured patients traumatic and non-traumatic etiologies (e.g., traumatic brain injury, anoxic brain injury, subarachnoid hemorrhage). Twelve patients will be recruited for the validation phase. The sample size estimation for the clinical trial based on a Student's t-test is 138 (2 groups of 69 patients) to reach a power of 80% to detect a statistically significant difference in the amplitude of alpha activity between active and sham groups, assuming a dropout/death rate of 20% and a significance level of 5%. These parameters are calculated according to a randomized, sham-controlled clinical trial comparing a 4-week tDCS protocol on patients with disorders of consciousness. The main outcome was a behavioral assessment, whereas this study's main outcome is neurophysiological, which is more sensitive to detect modulation effects. Additionally, this estimate will be readjusted according to the clinical pilot's results. The study protocol will be activated once the medical team states clinical stability for the patients and withdrawal of continuous sedation has surpassed a minimum of 24 hours, without recovery of responsiveness. Patients will participate in 7 consecutive experimental days including : Day 0: Baseline measurements: Blood samples ( pharmacological agents dosage, the plasma expression of glial fibrillary acidic protein (GFAP) and isolation of exosomes derived from neurons (EDNs), astrocytes (EDAs) and microglia (EDMs)), Behavioral outcomes (Coma Recovery Scale-Revised (CRS-R), Glasgow Coma Scale (GCS) and Full Outline of Unresponsiveness (FOUR) Score) will be additionally measured for Unresponsive Wakefulness patients), pupillometry (photo motor reflex), and actigraph installation. Days 1 to 5 (the following sequential procedure): CRS-R/FOUR/GCS Pupillometry (PLR) 5-minute resting-state EEG 20-minute tACS/sham 5-minute resting-state EEG Pupillometry (PLR) CRS-R 5-minute resting-state 60-minute post-tACS condition/sham condition 5-minute resting-state 120-minute post-tACS condition/sham condition Day 6: CRS-R Pupillometry (PLR) 5-minute resting-state EEG Day 7: After an interval of one-week post-5-day tACS/sham protocol, the following measurements will be acquired: CRS-R, Pupillometry (photo motor reflex), and 5-minute resting-state EEG. The actigraph will be withdrawn the during this same session. At 3,6 and 12 months post-tACS, phone assessments will be conducted to measure long-term functional recovery using the following tools: Glasgow Outcome Scale- Extended, Disability Rating Scale, Functional Independence Measure and Burden Scale for Family Caregivers.

Conditions

• Brain Injury Traumatic Severe
• Disorder of Consciousness
• Brain Injuries

Interventions

Type	Name	Description
DEVICE	Active Transcranial alternative current stimulation	GTEN 200 (Magstim-EGI, OREGON, USA). The current will be administered via an amplifier connected to an EEG system of 128-Channel Geodesic Sensor Net (Magstim-EGI, Oregon, USA) with sponge-based electrode nets. tACS stimulation will be applied for 20 minutes for 5 consecutive days via a bilateral electrode montage of 5 electrodes per hemisphere over parieto-occipital cortical sites. Specific stimulation electrodes for both conditions will be: \[right hemisphere: E83, E90, E96, E84, E91\] and for the \[left hemisphere: E58, E65, E70, E66, E59\]. The intensity of the applied alternative current (AC) will be a maximum of 1 mA peak-to-peak. The stimulation frequency will be adjusted to 10 Hz (median value of the alpha frequency band) for the tACS condition.
DEVICE	SHAM Transcranial alternative current stimulation	GTEN 200 (Magstim-EGI, OREGON, USA). The current will be administered via an amplifier connected to an EEG system of 128-Channel Geodesic Sensor Net (Magstim-EGI, Oregon, USA) with sponge-based electrode nets. SHAM stimulation will be applied for a 2-minute ramp-up, then the current will stop for 20 minutes, followed by a 2-minute ramp-down. This will be applied for 5 consecutive days via a bilateral electrode montage of 5 electrodes per hemisphere over parieto-occipital cortical sites. Specific stimulation electrodes for both conditions will be: \[right hemisphere: E83, E90, E96, E84, E91\] and for the \[left hemisphere: E58, E65, E70, E66, E59\]. The intensity of the applied alternative current (AC) will be a maximum of 1 mA peak-to-peak. The stimulation frequency will be adjusted to 10 Hz (median value of the alpha frequency band) for the ramp-up and down in the SHAM conditions.

Timeline

• Start date: 2023-09-01
• Primary completion: 2026-03-01
• Completion: 2026-03-01
• First posted: 2023-04-27
• Last updated: 2023-04-27