Modulation of Cortical Gamma Synchrony in Stroke (GAMMASTROKE)

Assessment and Modulation of Cortical Gamma Synchrony to Predict and Improve Stroke Recovery

In the last decades, the research in neuroimaging-informed stroke prognosis and treatment has had a little clinical impact, often because of the costs of bringing complex procedures to the bedside. Cerebral stroke remains the leading cause of disability, with 65% of survivors chronically impaired at 6 months. Gamma synchrony (GS) is a fundamental mechanism of cortical function and can be estimated and modulated in a simple, inexpensive, and reliable way. It has provided valuable and cost-effective guidance in several neuropsychiatric conditions. In previous studies, we developed simple yet robust methods for assessing and manipulating GS and proved its relationship with clinical impairment in preliminary data.

The aim of the present project is to predict and improve stroke recovery by leveraging cortical mapping and modulation of GS via transcranial alternating current stimulation (tACS), a safe and inexpensive technique. The project capitalizes on technology readily available to the Italian national health system.

Study Overview

• Status: Recruiting
• Conditions: Stroke
• Intervention / Treatment: Device: real tACS; Device: sham tACS

Detailed Description

The project will consist of 3 Work Packages (WPs):

• The aim of WP1 is to map the relationship between GS and clinical outcomes with EEG.
• The aim of WP2 is to translate GS assessment and modulation to bedside.
• The aim of WP3 is to modulate GS to improve rehabilitation outcomes.

• Study Type: Interventional
• Enrollment (Anticipated): 220
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Giorgio Arcara; Phone Number: 0412207594; Email: giorgio.arcara@hsancamillo.it

Study Locations

• Italy
  • Venice, Italy
    • Recruiting
    • IRCCS San Camillo Hospital
    • Contact: Valeria Camparini; Email: valeria.camparini@hsancamillo.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

The participants in this study will be 140 stroke patients rehabilitated at IRCCS San Camillo hospital. 80 will participate in the WP1 and the WP2, while 60 will participate in the WP3 study. In WP1, data will also be collected on 80 healthy volunteer participants, approximately the same age as the patients.

Inclusion Criteria (healthy participants)

- no neurological or psychiatric disorder

Inclusion Criteria (patients)

• right or left hemisphere damage
• unilateral stroke
• no comorbidities with psychiatric disorders

Exclusion Criteria (general):

• Diagnosis of epilepsy or family history up to the second degree with it
• Episodes of febrile convulsions or recurrent fainting
• Head trauma
• Presence of surgical clips or metal implants in the head
• Diagnosis of heart disease
• Presence of a cardiac pacemaker or artificial heart valve
• Presence of hearing aids/prostheses
• Hearing problems or tinnitus
• Vision problems not corrected with lenses (such as color blindness)
• Taking tricyclic antidepressant medications
• Taking neuroleptic medications
• Diagnosis of headache or migraine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: real tACS; Real tACS will be delivered by applying two conductive electrodes over the left and right central areas, for 30 minutes/day (Monday-to-Friday), for two weeks, with the following parameters: sinewaves at 40Hz, peak-to-peak amplitude=1mA, 3s ramping-up and ramping-down. Intensity will be lowered if perceived as uncomfortable.	Device: real tACS; The effect of transcranial alternating current stimulation (tACS) will be investigated in WP3. Patients will undergo standard intensive rehabilitation plus gamma tACS for two weeks.
Sham Comparator: sham tACS; Sham tACS will consist of only 30s of stimulation.	Device: sham tACS; In WP3, patients will undergo standard intensive rehabilitation plus sham tACS for two weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gamma synchrony Work Package 1 (WP1)	Gamma synchrony will be measured via exposure to amplitude-modulated 40Hz sounds (5 min, sequence of amplitude-modulated tones at 40 Hz, delivered via earplug binaurally). Gamma synchrony will be quantified as power of the EEG gamma band. Gamma synchrony will be measured at the baseline of the intervention (i.e., standard intensive rehabilitation at IRCCS S. Camillo Hospital)	baseline
Gamma synchrony Work Package 1 (WP1)	Gamma synchrony will be measured via exposure to amplitude-modulated 40Hz sounds (5 min, sequence of amplitude-modulated tones at 40 Hz, delivered via earplug binaurally). Gamma synchrony will be quantified as power of the EEG gamma band. Gamma synchrony will be measured immediately after the intervention (i.e., standard intensive rehabilitation at IRCCS S. Camillo Hospital)	immediately after the intervention
Gamma synchrony Work Package 3 (WP3)	Gamma synchrony will be measured via exposure to amplitude-modulated 40Hz sounds (5 min, sequence of amplitude-modulated tones at 40 Hz, delivered via earplug binaurally). Gamma synchrony will be quantified as power of the EEG gamma band. Gamma synchrony will be measured at the baseline of the intervention (i.e., standard intensive rehabilitation at IRCCS S. Camillo Hospital)	baseline
Gamma synchrony Work Package 3 (WP3)	Gamma synchrony will be measured via exposure to amplitude-modulated 40Hz sounds (5 min, sequence of amplitude-modulated tones at 40 Hz, delivered via earplug binaurally). Gamma synchrony will be quantified as power of the EEG gamma band. Gamma synchrony will be measured immediately after the intervention (i.e., standard intensive rehabilitation at IRCCS S. Camillo Hospital)	immediately after the intervention
Gamma synchrony (reduced number of EEG sensors). Work Package 2 (WP2)	Gamma synchrony will be measured via exposure to amplitude-modulated 40Hz sounds (5 min, sequence of amplitude-modulated tones at 40 Hz, delivered via earplug binaurally). Gamma synchrony will be quantified as power of the EEG gamma band. Gamma synchrony will be measured at the baseline of the intervention (i.e., standard intensive rehabilitation at IRCCS S. Camillo Hospital)	baseline
Gamma synchrony (reduced number of EEG sensors). Work Package 2 (WP2)	Gamma synchrony will be measured via exposure to amplitude-modulated 40Hz sounds (5 min, sequence of amplitude-modulated tones at 40 Hz, delivered via earplug binaurally). Gamma synchrony will be quantified as power of the EEG gamma band. Gamma synchrony will be measured immediately after the intervention (i.e., standard intensive rehabilitation at IRCCS S. Camillo Hospital)	immediately after the intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Behavioral performance (response times). Work Package 1 (WP1)	Participants' cognitive performance at neuropsychological tests will be measured. Behavioral performance will be measured in terms of response times (how fast the participants complete the task). Behavioral performance will be measured at the baseline of the intervention (i.e., standard intensive rehabilitation at IRCCS S. Camillo Hospital)	baseline
Behavioral performance (response times). Work Package 1 (WP1)	Participants' cognitive performance at neuropsychological tests will be measured. Behavioral performance will be measured in terms of response times (how fast the participants complete the task). Behavioral performance will be measured immediately after the intervention (i.e., standard intensive rehabilitation at IRCCS S. Camillo Hospital)	immediately after the intervention
Behavioral performance (response times). Work Package 3 (WP3)	Participants' cognitive performance at neuropsychological tests will be measured. Behavioral performance will be measured in terms of response times (how fast the participants complete the task). Behavioral performance will be measured at the baseline of the intervention (i.e., standard intensive rehabilitation at IRCCS S. Camillo Hospital)	baseline
Behavioral performance (response times). Work Package 3 (WP3)	Participants' cognitive performance at neuropsychological tests will be measured. Behavioral performance will be measured in terms of response times (how fast the participants complete the task). Behavioral performance will be measured immediately after the intervention (i.e., standard intensive rehabilitation at IRCCS S. Camillo Hospital)	immediately after the intervention
Behavioral performance (accuracy). Work Package 1 (WP1)	Participants' cognitive performance at neuropsychological tests will be measured. Behavioral performance will be measured in terms of accuracy (% of correct responses). Behavioral performance will be measured at the baseline of the intervention (i.e., standard intensive rehabilitation at IRCCS S. Camillo Hospital)	baseline
Behavioral performance (accuracy). Work Package 1 (WP1)	Participants' cognitive performance at neuropsychological tests will be measured. Behavioral performance will be measured in terms of accuracy (% of correct responses). Behavioral performance will be measured immediately after the intervention (i.e., standard intensive rehabilitation at IRCCS S. Camillo Hospital)	immediately after the intervention
Behavioral performance (accuracy). Work Package 3 (WP3)	Participants' cognitive performance at neuropsychological tests will be measured. Behavioral performance will be measured in terms of accuracy (% of correct responses). Behavioral performance will be measured at the baseline of the intervention (i.e., standard intensive rehabilitation at IRCCS S. Camillo Hospital)	baseline
Behavioral performance (accuracy). Work Package 3 (WP3)	Participants' cognitive performance at neuropsychological tests will be measured. Behavioral performance will be measured in terms of accuracy (% of correct responses). Behavioral performance will be measured immediately after the intervention (i.e., standard intensive rehabilitation at IRCCS S. Camillo Hospital)	immediately after the intervention

Collaborators and Investigators

• Sponsor: IRCCS San Camillo, Venezia, Italy
• Collaborators: Campus Bio-Medico University
• Investigators: Principal Investigator: Giorgio Arcara, IRCCS San Camillo Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2021
• Primary Completion (Anticipated): March 23, 2024
• Study Completion (Anticipated): March 23, 2024

Study Registration Dates

• First Submitted: March 16, 2023
• First Submitted That Met QC Criteria: April 13, 2023
• First Posted (Actual): April 26, 2023

Study Record Updates

• Last Update Posted (Actual): April 26, 2023
• Last Update Submitted That Met QC Criteria: April 13, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: tACS; gamma synchrony
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke
• Other Study ID Numbers: 2020.08

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No