TACS to Engage Theta-Gamma Coupling and Enhance Working Memory in Patients With MCI (tACS-MCI)

NCT06783283 | Recruiting

• 1 other identifier: 056-2023
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This study is looking at a new non-invasive brain stimulation methods called transcranial alternating current stimulation (tACS) to see if it can improve working memory and thinking processes in people with Mild Cognitive Impairment (MCI). tACS is a low-risk, non-painful, low electrical current that circulates through the brain of awake participants and stimulates their brain cells. Participants must be 60 years of age and have a diagnosis of mild cognitive impairment. Participants will undergo treatment sessions that range from 1 to 1.5 hours at CAMH, 5 days a week, over a total of 2 weeks. In addition, participants will complete clinical and cognitive assessments and bloodwork at baseline and again after treatment.

Conditions

Mild Cognitive Impairment (MCI)

Keywords

Memory Impairment; Executive Function; Transcranial Alternating Stimulation; Neuroplasticity; Electroencephalography; Working Memory; Cognition; Prefrontal Cortex; Transcranial Electrical Stimulation; Dementia; Alzheimer's Disease; Temporal Cortex

Outcome Measures

Primary Outcomes (2)

• Percentage of All Screened Participants

  Recruitment (percentage of all screened participants) will be examined. Hypothesis: At least 30% of screened participants will agree and be eligible to receive the intervention they are assigned to, i.e., tACS.

  Through treatment completion, at the end of 2-week intervention.

• Percentage of All Enrolled Participants

  Retention will be examined. Hypothesis: At least 70% of participants will attend at least 80% of their treatment sessions.

  Through treatment completion, at the end of 2-week intervention.

Secondary Outcomes (3)

• Theta-gamma Coupling

  Through treatment completion, at the end of 2-week intervention.

• N-Back

  Through treatment completion, at the end of 2-week intervention.

• Mediation of TGC on changes in N-back performance

  Through treatment completion, at the end of 2-week intervention.

Other Outcomes (5)

• PASAT

  Through treatment completion, at the end of 2-week intervention.

• Neuroimmune response

  Through treatment completion, at the end of 2-week intervention.

• Neuroimmune response

  Through treatment completion, at the end of 2-week intervention.

Study Arms (2)

Active tACS

ACTIVE COMPARATOR

After completing the Baseline testing at Visit 1 and N-back EEG at Visit 2, MCI participants randomized to the active condition will receive a 10-session course of tACS (Visits 4-13), followed by a follow-up assessment, post intervention, at Visit 14.

Device: Transcranial Alternating Current Stimulation

Sham tACS

SHAM COMPARATOR

After completing the Baseline testing at Visit 1 and N-back EEG at Visit 2, MCI participants randomized to the sham condition will receive a 10-session course of sham-tACS (Visits 4-13), followed by a follow-up assessment, post intervention, at Visit 14.

Device: Sham tACS

Interventions

Transcranial Alternating Current Stimulation DEVICE

Transcranial Alternating Current Stimulation (tACS) is a non-invasive electrical stimulation that will be used to stimulate the dorsolateral prefrontal cortex (dlPFC) and temporal cortices and in turn enhance Theta-Gamma Coupling (TGC) and working memory in Mild Cognitive Impairment (MCI). Each participant will receive daily stimulation for 10 days. To deliver the tACS, multiple electrodes embedded in a cap placed on the participant's head. Sham-tACS will follow the same procedure.

Also known as: tACS

Active tACS

Sham tACS DEVICE

During sham-tACS, the device will ramp up to the desired intensity over 60 seconds, and then will immediately ramp down, and the stimulation will be shut off, until the end of the session. At the end of the session, the device will again ramp up for 60 seconds and then ramp down. Sham-tACS will also target dlPFC and temporal cortices (similar to active). Each participant will receive daily sham-tACS for 10 days. To deliver the sham-tACS, multiple electrodes will be embedded in a cap placed on the participant's head.

Sham tACS

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 60 years or above,
• Diagnosis of MCI due to AD using the core clinical criteria by the National Institute on Aging and Alzheimer's Association for MCI participants (NIA-AA) and ascertained by a study investigator. The following checklist will be used to ascertain the MCI diagnosis:
• Cognitive concern reflecting a change in cognition reported by patient or informant or clinician (i.e., historical or observed evidence of decline over time)
• Not demented ascertained using the study investigator opinion.
• No vascular, traumatic, or medical causes of cognitive decline ascertained using the study investigator opinion.
• Evidence of longitudinal decline in cognition, when feasible, and ascertained using the study investigator opinion.
• Objective evidence of single or multi domain MCI, where single domain MCI refers to deficits using neuropsychology (NP) battery on only one of the cognitive domains (Speed of Processing; Working Memory; Executive Functioning; Verbal Memory; Visual Memory; Language) and multi domain MCI refers to deficits in more than one of these domains. To determine impairment in one or more cognitive domain, after the NP battery is administered and double scored, a consensus meeting will be held with the Research Analyst/Fellow, the study Principal Investigator and the study Neuropsychologist during which eligibility will be discussed. The meeting attendees will take into consideration the participant's education, parental education, pre-morbid IQ, physician's assessment and NP scores to determine if the participant has impairment in one or more cognitive domain.
• Willingness to provide informed consent,
• Ability to read and communicate in English (with corrected vision and hearing, if needed)

You may not qualify if:

• Current use of an acetylcholine esterase inhibitor or memantine ascertained via participant's report, Medication List, or Electronic Medical Record (EMR).
• Major Depressive Disorder with active symptoms in the last 3 months ascertained using the Mini International Neuropsychiatric Interview (MINI), or Structured Clinical Interview for DSM-5 (SCID), or EMR.
• A lifetime diagnosis of bipolar disorder; intellectual disability; or a psychotic disorder ascertained using the MINI or SCID, or EMR.
• Substance use disorder active in the last 3 months ascertained using the MINI or SCID, or EMR.
• Any other DSM-5 diagnosis ascertained using the MINI or SCID, or EMR, that may be associated with prefrontal cortical dysfunction as ascertained using a study investigator opinion.
• Current anticonvulsant use due to its impact on brain stimulation induced activity and ascertained using a Medication List or EMR. An exception will be made if they are taking gabapentin or pregabalin AND if the dose had been stable for at least 4 weeks prior to study entry AND if prescribed for chronic pain.
• Current benzodiazepine use of more than what is equivalent to lorazepam 2 mg/day as ascertained using a Medication List. This is due to their known pro-GABAergic activity and the suppressive effect of GABAergic agents on cortical plasticity
• Any contraindication to MRI or contraindication to tACS (e.g., cardiac pacemaker, acoustic device, history of seizures) ascertained using the tACS Safety Screen (tSS)

Sponsors & Collaborators

• Soterix Medical: collaborator
• Centre for Addiction and Mental Health: lead

Study Sites (1)

Centre for Addiction and Mental Health

Toronto, Ontario, M6J 1H4, Canada

RECRUITING

Related Links

• Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teaching hospital, fully affiliated with the University of Toronto, and a PAHO/WHO Collaborating Centre

MeSH Terms

Conditions

Cognitive Dysfunction; Memory Disorders; Dementia

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Study Officials

• Sanjeev Kumar, MD

  Centre for Addiction and Mental Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sanjeev Kumar, MD

CONTACT

416-535-8501; Sanjeev.Kumar@camh.ca

Dewi Clark, MHSc

CONTACT

416-535-8501; dewi.clark@camh.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study will be completed under triple-blind conditions. First, participants will be blind to whether they are randomized to the active treatment (tACS) or sham group (sham-tACS), which is achievable because it is difficult to distinguish the active treatment interventions from the control conditions. Second, the investigator team (investigators and interventionists delivering the 10-session course) will be blind to group assignment. Third, the outcomes assessors conducting the clinical, cognitive and EEG assessments at baseline and follow-ups will be blind to group assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: In a 1x1 factorial Randomized Controlled Trial (RCT), the investigators will randomize 20 MCI participants to one of the two treatment arms: tACS and sham-tACS, with 10 participants in each group. tACS will be delivered bilaterally to the PFC and temporal cortices. Each participant will receive daily stimulation for 10 days. Working memory and TGC during working memory performance will be assessed at baseline and following the last day of the study intervention. Working memory will be assessed using the N-back task and TGC using EEG during N-back performance.

Study Record Dates

• First Submitted: December 12, 2024
• First Posted: January 20, 2025
• Study Start: January 2, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: After publishing the results of the study.
• Access Criteria: New proposals approved by ethics board, data will be shared using Centre for Addiction and Mental Health databank.

Locations

CA (1)