Targeting Brain Physiology to Treat Neuropsychiatric Symptoms of Dementia Using TMS-EEG and tDCS

NCT03846492 | Active Not Recruiting FDA Device

• 1 other identifier: 093/2018
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

Agitation and aggression impose a tremendous burden on the individuals living with dementia, their families, caregivers, and healthcare systems. Neuropsychiatric symptoms of dementia (NPS) affect up to 80% of patients with Alzheimer's dementia (AD). The mechanisms of agitation in AD are poorly understood and the current interventions are only modestly effective while having serious adverse effects. In this study, the investigators propose to assess the mechanisms and treatment of neuropsychiatric symptoms in AD with the use of non-invasive, brain stimulation approaches. By applying magnetic stimulation to the surface of the head (transcranial magnetic stimulation - TMS) combined with electroencephalography (EEG), the investigators will be able to study the mechanisms of agitation and advance our understanding of AD. Further, the investigators will evaluate if transcranial direct current stimulation (tDCS) is effective to treat agitation dementia.

Conditions

Alzheimer Disease; Dementia, Mixed; Dementia; Behavior Problem; Dementia, Alzheimer Type

Keywords

Dementia; Transcranial Magnetic Stimulation; Transcranial Direct Current Stimulation; tDCS; TMS; TMS-EEG; MRI; Agitation; Alzheimer's disease; Neuropsychiatric symptoms; Agitation in dementia; Mixed dementia; Non-invasive brain stimulation

Outcome Measures

Primary Outcomes (1)

• Long Interval Cortical Inhibition (LICI), a TMS paradigm, will be used to assess the extent of cortical inhibition

  LICI will be measured using single and paired TMS pulses applied to the Dorsolateral Prefrontal Cortex (DLPFC). LICI will be compared between the 3 groups (AD, AD+agitation and healthy comparators).

  Baseline

Secondary Outcomes (9)

• Short Interval Cortical Inhibition (SICI), another TMS paradigm, will be used to assess the extent of cortical inhibition

  Baseline

• The rate of successful completion of the 2 week tDCS treatment course

  Approximately 2 weeks after baseline

• Effects of a 2 week course of tDCS on cortical/inhibition balance

  Approximately 2 weeks after baseline

• Change in clinical symptoms of agitation as assessed by the Clinical Global Impression of Change (CGIC)

  Approximately 2 and 4 weeks after baseline

• Change in clinical symptoms of agitation as assessed by the Neuropsychiatric Inventory (NPI) agitation/aggression subscale score

  Approximately 2 and 4 weeks after baseline

Study Arms (2)

Active tDCS

EXPERIMENTAL

The direct current will be delivered at 2 mA intensity via rubber electrodes in saline- soaked sponges for 30 min per day for 2 weeks, 5 days/week. Inhibitory stimulation will be delivered to the frontal lobes.

Device: Transcranial Direct Current Stimulation (tDCS)

sham tDCS

SHAM COMPARATOR

Sham tDCS will use the same parameters except that the device will automatically turn off after a certain duration.

Device: Transcranial Direct Current Stimulation (tDCS)

Interventions

Transcranial Direct Current Stimulation (tDCS) DEVICE

tDCS is a non-invasive brain stimulation modality that does not require general anesthesia or surgical implantation of a device. tDCS utilizes low intensity electrical current either to increase cortical excitability with an anodal electrode or to suppress cortical excitability with a cathodal electrode. It uses 3 AAA batteries to deliver direct current via rubber electrodes enclosed in saline soaked sponges.

Active tDCS; sham tDCS

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 50 years or older.
• Participant or substitute decision maker able and willing to provide informed consent.
• Dementia due to probable or possible AD as defined by NIA-AA criteria.
• Presence of mild to moderate agitation and/or aggression as defined by: Agitation in cognitive disorders. International Psychogeriatric Association Provisional Consensus Clinical and Research Definition.
• Availability of a support person to accompany the participant to study appointments and provide collateral information as needed.
• If taking medication for neuropsychiatric symptoms, the dose should be stable for at least 1 week.

You may not qualify if:

• Psychiatric diagnosis other than dementia significantly impacting the presentation.
• Presence of delirium or other acute medical condition significantly contributing to agitation/aggression or making the study participation unsafe for a participant.
• Any contraindication to TMS or tDCS.
• Any other condition that in the opinion of principal investigator will make the study participation unsafe or non-feasible for the participant.
• Currently taking anticonvulsants or benzodiazepines at a dose sufficient to cause interference with TMS-EEG.
• Participants with AD without aggression
• Healthy comparator participants
• Age 50 years or older.
• Able and willing to provide informed consent.
• Free from any significant neurological disorder.
• Lifetime DSM-5 diagnosis other than simple phobias or adjustment disorder.
• Any Contraindication to TMS.
• Currently taking anticonvulsants or benzodiazepines at a dose sufficient to cause interference with TMS-EEG.

Sponsors & Collaborators

• BrightFocus Foundation: collaborator
• Centre for Addiction and Mental Health: lead

Study Sites (1)

Centre for Addiction and Mental Health

Toronto, Ontario, M6J 1H4, Canada

Location

MeSH Terms

Conditions

Alzheimer Disease; Mixed Dementias; Dementia; Mental Disorders; Psychomotor Agitation; Aberrant Motor Behavior in Dementia

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Dyskinesias; Neurologic Manifestations; Psychomotor Disorders; Neurobehavioral Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

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

Study Officials

• Sanjeev Kumar, MD, FRCPC

  Centre for Addiction and Mental Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Psychiatrist and Clinician Scientist, Medical Head of Geriatric Clinical Research

Model Details: Individuals with AD + agitation will receive a 2 week course of active/sham cathodal tDCS to frontal brain region in a double blind 1:1 randomized control design.

Study Record Dates

• First Submitted: February 8, 2019
• First Posted: February 19, 2019
• Study Start: April 24, 2019
• Primary Completion: April 8, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

CA (1)