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Alzheimer DiseasetTEDNCT03846492

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

A study testing Transcranial Direct Current Stimulation (tDCS) in people with Alzheimer Disease and Dementia, Mixed, run by Centre for Addiction and Mental Health at 1 site in Canada.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 50 years and olderHealthy volunteers can take part
Conditions the study is for
Alzheimer Disease, Dementia, Mixed, Dementia
What is being tested?
Transcranial Direct Current Stimulation (tDCS)
Type of treatment
Medical device
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
90 participants
Where
1 siteCanada
Study dates
24 Apr 2019to 31 Dec 2026
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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.
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  • Age 50 years or older.
  • Able and willing to provide informed consent.
  • Free from any significant neurological disorder.

Who cannot join

  • 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
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  • All the above inclusion/exclusion criteria except meeting the inclusion criterion 4 pertaining to agitation/aggression. Participants with significant agitation/aggression will be excluded from this group.
  • Healthy comparator participants
  • 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.

Trial locations and contacts

1 site in 1 country.

Canada1 site
  • Centre for Addiction and Mental Health

    Toronto, Ontario, M6J 1H4

Other trials in Canada

About this study

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.

Read the detailed description

Alzheimer's dementia (AD) and related neurodegenerative diseases are inflicting a global healthcare crisis. Neuropsychiatric symptoms including agitation and aggression affect up to 80% of patients with AD. Among these symptoms, agitation and aggression are the most burdensome for patients, families, caregivers, and the health care system. 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. Agitation/aggression is associated with abnormalities in the balance of cortical excitation/inhibition. Transcranial magnetic stimulation (TMS) using single and paired pulse TMS paradigms such as long interval cortical inhibition (LICI) and short interval intracortical inhibition (SICI) can assess this cortical excitation/inhibition balance in vivo. The investigators will use TMS, combined with electroencephalography (EEG), to assess cortical excitation/inhibition balance in the dorsolateral prefrontal cortex (DLPFC) of participants with AD with and without agitation/aggression and age matched healthy comparators.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that uses a very low intensity electric current to modulate cortical excitability and brain plasticity. tDCS can restore excitation and inhibition balance by altering GABA and glutamate activity in the brain. tDCS can be safely administered to awake persons and is very well tolerated. Studies in healthy individuals and patients with AD have shown that tDCS applied to frontal brain regions can enhance cognitive function. Further, tDCS applied to frontal brain regions can improve depressive symptoms. The effects of tDCS on neuropsychiatric symptoms are not known. In this study, the investigators will use tDCS applied to the frontal brain regions to target deficits in inhibition and symptoms of agitation/aggression in AD.

This study will be done over a period of 3 years at Centre for Addiction and Mental Health Geriatric Psychiatry Division and Temerty Centre for Therapeutic Brain Intervention. The investigators will recruit and enroll 30 individuals with AD + Agitation (mild to moderate agitation), 30 individuals with AD without agitation and 30 older healthy individuals. Medical work up will be done as part of clinical care prior to study enrollment to rule out medical causes of agitation. Clinical and cognitive assessments will be performed to characterize participants at baseline. The investigators will assess cortical inhibition using TMS EEG at baseline in the three groups. Individuals with AD + agitation will then receive a 2 week course of active/sham cathodal tDCS to frontal brain region in a double blind 1:1 randomized control design. Assessment of cortical inhibition using measures identical to baseline will be done at the end of tDCS course. The investigators will also repeat clinical and cognitive assessments after tDCS course and 2 weeks later. Measures of cortical inhibition will first be compared between HC and AD, and between AD and AD + Agitation groups. The treatment effects on clinical symptoms, cortical inhibition and the rate adverse events will be compared between active and sham tDCS groups.

During the Covid-19 pandemic, the study has been modified to be administered in a hybrid manner to accommodate both in-person and virtual assessments. Clinical and cognitive assessments can be done in-person or remotely. The initial tDCS course will be conducted in-person with the research staff. The remaining tDCS intervention will be completed onsite or at the participant's home with virtual supervision from the research team.

Being tested
Transcranial Direct Current Stimulation (tDCS)
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
Medical subject headings
Alzheimer Disease, Mixed Dementias, Dementia, Mental Disorders, Psychomotor Agitation, Aberrant Motor Behavior in Dementia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 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.

Study groups in NCT03846492
Study groupRoleWhat they receive
Active tDCSExperimentalThe 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.
Receives: Device: Transcranial Direct Current Stimulation (tDCS)
sham tDCSSham comparatorSham tDCS will use the same parameters except that the device will automatically turn off after a certain duration.
Receives: Device: Transcranial Direct Current Stimulation (tDCS)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: Baseline

Secondary outcomes (9)
  1. Short Interval Cortical Inhibition (SICI), another TMS paradigm, will be used to assess the extent of cortical inhibition

    SICI will be measured using single and paired TMS pulses applied to the DLPFC and motor cortex. SICI will be compared between the 3 groups (AD, AD+agitation and healthy comparators).

    Measured: Baseline

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

    This will be assessed by the successful completion of the intervention in at least 80% of participants without any treatment associated serious adverse effects.

    Measured: Approximately 2 weeks after baseline

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

    TMS using single and paired pulse paradigms, such as LICI and SICI, will be repeated after completion of the 2 week course of tDCS.

    Measured: Approximately 2 weeks after baseline

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

    The clinical symptoms will be assessed at baseline, after completion of the tDCS intervention and at follow up 2 weeks after last tDCS session. CGIC scores range from 0-7, higher scores indicating worsening compared to baseline.

    Measured: Approximately 2 and 4 weeks after baseline

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

    The clinical symptoms will be assessed at baseline, after completion of the tDCS intervention and at follow up 2 weeks after last tDCS session. NPI frequency of symptoms are rated on a scale of 0 - 4 (Higher scores indicate symptoms occur more frequently). Severity / intensity of symptoms are rated on a scale of 0 to 3 (Higher scores indicate greater severity of symptoms). Caregiver distress is rated on a scale of 0 to 5 (Higher scores indicate increased caregiver distress).

    Measured: Approximately 2 and 4 weeks after baseline

  6. Change in clinical symptoms of agitation as assessed by the Cohen Mansfield Agitation Inventory scores (CMAI)

    The clinical symptoms will be assessed at baseline, after completion of the tDCS intervention and at follow up 2 weeks after last tDCS session. CMAI-frequency score ranges between 29 to 203 and CMAI-disruptiveness ranges from 29 to 145 for each category. Higher scores indicate worsening of symptoms.

    Measured: Approximately 2 and 4 weeks after baseline

  7. Assess brain structure using Magnetic Resonance Imaging (MRI)

    Brain structure (e.g. cortical atrophy and white matter integrity) will be compared between the 3 groups (AD, AD+agitation and healthy comparators).

    Measured: Baseline

  8. Assess resting state connectivity using Functional Magnetic Resonance Imaging (fMRI)

    Resting state connectivity using Brain Oxygen Level Dependent (BOLD) signal will be compared between the 3 groups (AD, AD+agitation and healthy comparators).

    Measured: Baseline

  9. Assess GABA and glutamate levels using Magnetic Resonance Spectroscopy (MRS)

    GABA and glutamate concentrations will be measured in the left DLPFC and compared between the 3 groups (AD, AD+agitation and healthy comparators).

    Measured: Baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Feb 2019
  2. Study start24 Apr 2019
  3. Primary completion8 Apr 2025
  4. Study completion31 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
90 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03846492
Sponsor's protocol ID
093/2018
Acronym
tTED
Status last verified
Apr 2026
First submitted
8 Feb 2019
Last updated
13 Apr 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
Yes

Questions about this trial

What is this clinical trial studying?

A study testing Transcranial Direct Current Stimulation (tDCS) in people with Alzheimer Disease and Dementia, Mixed, run by Centre for Addiction and Mental Health at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 13 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Long Interval Cortical Inhibition (LICI), a TMS paradigm, will be used to assess the extent of cortical inhibition (time frame: Baseline). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2026.

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