Therapeutic Improvement in People With Schizophrenia Undergoing tACS/CBTp (Transcranial Alternating Current Stimulation Applied Pre-cognitive Behavioral Therapy for Psychosis) Associated to Usual Medication Regimen

NCT06889025 | Not Yet Recruiting

• 2 other identifiers: HSREB File No: 6044118TRAQ DSS file - #6036290
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators are proposing a new, non-invasive therapeutic model using transcranial alternative current stimulation (tACS), to augment cognitive behavioral therapy for psychosis (CBTp) efficacy in individuals with schizophrenia (SZ). Using EEG brain oscillation activity, as a biomarker of the progression of cognitive deficits in SZ, the investigators aim to understand if addressing the oscillation perturbations could reduce the cognitive deficits. The investigators are using heart rate variability (HRV) as a biomarker of improvement of somatic and mental health. The investigators are aiming also for an analysis through a GBA+ lens, by using along with specific tests for psychosis (PANSS, NSA-16, etc.), the BEM Sex Role Inventory. Considering that cognitive and emotional status is gender dependent, the investigators expect that the therapeutic response could be gender specific. This is a prospective, randomized, repeated-measures, single-blind study design. Pre-intervention, eligible participants will be randomly assigned to one of two treatment arms. Arm 1 (tACS/CBTp n=14); Arm 2 (sham tACS/CBTp, n=14; tACS is sham, but CBTp is active). Intervention (16 weeks): participants in Arms 1 and 2 will receive once weekly tACS/ CBTp or sham tACS/CBTp. Post-intervention: follow-up visits at 4- and 12-weeks post-intervention (with a tACS/CBTp booster session provided each time). The chart review will search for: comorbid metabolic conditions, lab work abnormalities (glycemic level, Hb A, cholesterol), substances use, BMI, type of medication, side effects. Expected outcomes: Participants in Arm 1 will show a better improvement in psychosocial assessment scores, electrical brain activity (tendency to organize the neural oscillations in the gamma frequency range, mainly in frontal lobes) and heart activity (increased HRV). The timeline for recruitment, treatment and follow-up, is 18 months, followed by six months for data analysis, dissemination activities. Population: Individuals with SZ (DSM V criteria) stratified by age and sex. The investigators expect 150 potentially eligible patients from PCH-MHS, with 28 participants consenting to participate.

Conditions

Schizophrenia; Schizoaffective Disorder

Keywords

Schizophrenia; tACS; CBTp

Outcome Measures

Primary Outcomes (3)

• PANSS (Positive and Negative Symptoms of Schizophrenia Scale)

  The PANSS is a standardized clinical interview that rates the presence and severity of positive and negative symptoms and general psychopathology for people with schizophrenia within the past week. The scale consists of 30 items: seven positive, seven negative, and 16 general psychopathology symptoms. The symptom severity for each item is rated according to a 7-point scale (1 = absent; 7 = extreme) to best describe the symptom's presentation. The clinical interview takes approximately 45 minutes. The patient is rated from 1 to 7 on 30 different symptoms based on the discussion and reports of family members or primary care hospital workers. As 1 is the lowest score for each item, a patient can not score lower than 30 for the total PANSS score. Scores are often given separately for positive items, negative items, and general psychopathology.

  Positive and Negative Symptoms of Schizophrenia scale will be applied at: Visit 1, Screening (Week 0); Visit 4, End of intervention (Week 17); Visit 5,Follow-up 1 (Week 21); Visit 6 Follow-up 2 (Week 29).

• NSA-16 (Negative Symptom Assessment)

  The NSA-16 assesses the presence, severity, and range of negative symptoms associated with schizophrenia. For rapid clinical assessment or screening of patients for negative symptoms, the NSA-4 was developed as a simplified version, retaining only 4 of the 16 items: restricted speech quantity, reduced emotion, reduced social drive, and reduced interests. Each of the four items and the overall global negative symptoms is rated on a 1 to 6-point scale where '1' represents no reduction from normal behaviors associated with the item and '6' represents a severe reduction in or absence of the behavior, with markedly impaired functionality. With respect to overall accuracy and predictive validity, the NSA-4 is comparable to the NSA-16.

  Negative Symptom Assessment-16: Visit 2, Baseline (Week 1); Visit 4, End of intervention (Week 17); Visit 5, Follow-up 1 (Week 21); Visit 6 Follow-up 2 (Week 29).

• CFS (Cognitive Flexibility Scale)

  The CFS assesses cognitive flexibility as a factor that facilitates the individual's adaptability towards events. Cognitive flexibility refers to a person's awareness that different communication styles exist in every situation and the person's willingness and self-efficacy to use different communicative styles. The scale has 12 items pertaining to the three elements of cognitive flexibility: a person's awareness of alternative communicative styles, willingness to be communicatively flexible, and self-efficacy in being communicatively flexible. The scale utilizes a 6-point Likert-type scale for each item (with 6 as "strongly agree," 5 as "agree," 4 as "slightly agree," 3 as "slightly disagree," 2 as "disagree," and 1 as "strongly disagree"). The total score was used to calculate a global score ranging from 12 to 72, with questions 2, 9, 11, and 12 being reverse-coded. A higher score indicates higher cognitive flexibility.

  Cognitive Flexibility Scale: Visit 2, Baseline (Week1 ); Visit 3 Mid point of intervention (Week 9); Visit 4, End of intervention (Week 17); Visit 5, Follow-up 1 (Week 21); Visit 6, Follow-up 2 (Week 29).

Secondary Outcomes (10)

• Heart Rate Variability (HRV)

  The Heart Rate Variability will be determined at Visit 2, Week 1, before and immediately after the first intervention (tACS/CBTp); it will be determined also pre and post the 16th intervention, Visit 4, Week 17.

• Electroencephalogram (EEG)

  Electroencephalogram will be performed at the Visit 1, Screening (Week 0) and Visit 5 End of intervention (Week 17) - before and at the end of intervention (the 16 tAC/CBTp sessions)

• World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0)

  The WHODAS 2.0 will be performed at: Visit 2, Baseline (Week 1), Visit 4, End of intervention (Week 17), Visit 5, Follow-up 1 (Week 21), Visit 6, Follow-up 2 (Week 29).

• The Quality-of-Life Enjoyment and Satisfaction Questionnaire Short Form (Q-Les-Q-SF)

  The Q-Les-Q-SF will be performed at: Visit 2, Baseline (Week 1); Visit 3 Mid-way intervention (Week 9), Visit 4 End of intervention (Week 17); Visit 5 Follow-up 1 (Week 21); Visit 6 Follow-up 2 (Week 2.9)

• Brief Betrayal Trauma Survey (BBTS)

  Brief Betrayal Trauma Survey will be performed at Visit 2, Baseline.

Other Outcomes (2)

• Eligibility Screening Measures: Columbia Suicide Severity Rating Scale

  At Screening, Visit 1(Week 0).

• Eligibility Screening Measures: The Montreal Cognition Assessment (MoCA), for participants over age of 65.

  The Montreal Cognition Assessment MoCA will be performed at Visit 1, Screening (Week 0), to participants over age of 65 (to exclude a possible cognitive decline).

Study Arms (2)

tACS/CBTp, both active/ intervention

EXPERIMENTAL

n=14; participants living with schizophrenia/schizoaffective disorder, stable under their usual medication; tACS (gamma band electric stimulation) will be applied the first 20 minutes of the CBTp session (then the device remains in place, but the electric stimulation will be automatically stopped). The CBTp will continue up until a total of 50 minutes/session.

Other: Experimental: tASC/CBTp: gamma band electric stimulation for 20 minutes at the beginning of the CBTp session

Sham tACS and CBTp (only CBTp active, intervention)

SHAM COMPARATOR

n=14, same diagnosis population, gender and age matched; sham tACS, CBTp for 50 minutes/session.

Other: Sham Comparator

Interventions

Experimental: tASC/CBTp: gamma band electric stimulation for 20 minutes at the beginning of the CBTp session OTHER

For the transcranial stimulation we will use the tES device from NeuroMyst,. The gamma pulses are delivered to a study participant via stimulating electrodes positioned at participant's head according to the required technique. The tACS will be applied the first 20 minutes from the classic CBTp session for the experimental group.

tACS/CBTp, both active/ intervention

Sham Comparator OTHER

For the Sham group the investigators will use the same tES device from NeuroMyst. The Sham stimulation will be applied only for a few seconds in Sham group. The CBTp will follow the same protocol for both arms.

Sham tACS and CBTp (only CBTp active, intervention)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals, with at least 5 years duration of illness, that meet diagnostic criteria for schizophrenia or schizoaffective disorder according to the Diagnostic and Statistical Manual for Mental Disorders-5 and at least one residual positive symptom (as determined by the referring physician);
• no change in medication regimen for at least 1 months (minor dose adjustments and/or change in medication involving symptoms as sleep, anxiety or medical symptoms such as fever, pain, are permitted);
• all genders between ages 18-65 (participants 65+ may be eligible depending on performance on cognitive assessment);
• ability to understand English with reading level at or above grade 6;
• able to understand and comply with the requirements of the study;
• provision of written informed consent.

You may not qualify if:

• current illicit drug substance abuse;
• current suicidal ideation;
• current enrollment in CBTp or other formalized psychosocial interventions;
• undergone vagotomy or surgery upon the vagus nerve;
• comorbid neurological condition;
• severe or moderate intellectual disability;
• currently undergoing hormone therapy;
• under age 18.

Sponsors & Collaborators

• Felicia Iftene: lead
• Providence Care Hospital - Providence Care: collaborator
• Queen's University: collaborator

Study Sites (1)

Providence Care Hospital

Kingston, Ontario, K7L7X3, Canada

Location

Related Publications (7)

• Tsuchimoto R, Kanba S, Hirano S, Oribe N, Ueno T, Hirano Y, Nakamura I, Oda Y, Miura T, Onitsuka T. Reduced high and low frequency gamma synchronization in patients with chronic schizophrenia. Schizophr Res. 2011 Dec;133(1-3):99-105. doi: 10.1016/j.schres.2011.07.020. Epub 2011 Aug 16.

  PMID: 21849245 BACKGROUND

• Benussi A, Cantoni V, Cotelli MS, Cotelli M, Brattini C, Datta A, Thomas C, Santarnecchi E, Pascual-Leone A, Borroni B. Exposure to gamma tACS in Alzheimer's disease: A randomized, double-blind, sham-controlled, crossover, pilot study. Brain Stimul. 2021 May-Jun;14(3):531-540. doi: 10.1016/j.brs.2021.03.007. Epub 2021 Mar 21.

  PMID: 33762220 BACKGROUND

• Turner DT, Burger S, Smit F, Valmaggia LR, van der Gaag M. What Constitutes Sufficient Evidence for Case Formulation-Driven CBT for Psychosis? Cumulative Meta-analysis of the Effect on Hallucinations and Delusions. Schizophr Bull. 2020 Sep 21;46(5):1072-1085. doi: 10.1093/schbul/sbaa045.

  PMID: 32221536 BACKGROUND

• Jones M, McDermott B, Oliveira BL, O'Brien A, Coogan D, Lang M, Moriarty N, Dowd E, Quinlan L, Mc Ginley B, Dunne E, Newell D, Porter E, Elahi MA, O' Halloran M, Shahzad A. Gamma Band Light Stimulation in Human Case Studies: Groundwork for Potential Alzheimer's Disease Treatment. J Alzheimers Dis. 2019;70(1):171-185. doi: 10.3233/JAD-190299.

  PMID: 31156180 BACKGROUND

• Best MW, Milanovic M, Iftene F, Bowie CR. A Randomized Controlled Trial of Executive Functioning Training Compared With Perceptual Training for Schizophrenia Spectrum Disorders: Effects on Neurophysiology, Neurocognition, and Functioning. Am J Psychiatry. 2019 Apr 1;176(4):297-306. doi: 10.1176/appi.ajp.2018.18070849. Epub 2019 Mar 8.

  PMID: 30845819 BACKGROUND

• Farcas A, Iftene F. Findings, limitations and new directions in tACS studies in schizophrenia research: A scoping review. J Psychiatr Res. 2022 Jul;151:291-298. doi: 10.1016/j.jpsychires.2022.04.036. Epub 2022 Apr 29.

  PMID: 35525231 BACKGROUND

• Iftene F, Farcas A, O'Brien S, Bowie CR, Best M, Ayonrinde O, Landry T, Carlson J, Davidson S, Rodgerson E, Theis A. Therapeutic Improvement in People with Schizophrenia Undergoing tACS/CBTp (Transcranial Alternating Current Stimulation /Cognitive Behavioural Therapy for Psychosis) Associated with Usual Medication Regimen: Protocol for a Pilot, Randomized, Single-Blind Trial. JMIR Res Protoc. 2025 Nov 21. doi: 10.2196/80593. Online ahead of print.

  PMID: 41273718 DERIVED

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Study Officials

• Felicia Iftene, Associate Professor, Md, PhD

  Department of Psychiatry, Queen's University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Felicia Iftene, MD, PhD, FRCPC; Associate Prof

CONTACT

613-484-7330; iftenef@providencecare.ca

Adriana Farcas, PhD, Clinical Neuroscientist

CONTACT

613--893-3362; farcasa@providencecare.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dr. Felica Iftene, Associate Professor, Department of Psychiatry, Queen's University

Model Details: Mandatory Non-Experimental Procedures: 16 individual-basis (with duration of 50 minutes), weekly sessions (a form of talk therapy named cognitive behavioral therapy for psychosis) and a booster session of CBTp at each follow up (one month and three after intervention). Mandatory Experimental Procedures The tASC with gamma band electric stimulation for 20 minutes at the beginning of the CBTp session is considered experimental and will only be done as part of this study. The combination of tASC and CBTp intervention will be applied to the two different groups: one with gamma band electric stimulation for 20 minutes at the beginning of the CBTp session and another group with sham tACS/CBTp (the tACS is sham, but the CBTp is intervention).

Study Record Dates

• First Submitted: March 10, 2025
• First Posted: March 21, 2025
• Study Start: July 24, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: July 24, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)