Alzheimer Disease Clinical Trial
— tTEDOfficial title:
Targeting Brain Physiology to Treat Neuropsychiatric Symptoms of Dementia Using TMS-EEG and tDCS
NCT number | NCT03846492 |
Other study ID # | 093/2018 |
Secondary ID | |
Status | Recruiting |
Phase | N/A |
First received | |
Last updated | |
Start date | April 24, 2019 |
Est. completion date | June 2025 |
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.
Status | Recruiting |
Enrollment | 90 |
Est. completion date | June 2025 |
Est. primary completion date | March 2025 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 50 Years and older |
Eligibility | Participants with AD+Agitation Inclusion: 1. Age 50 years or older. 2. Participant or substitute decision maker able and willing to provide informed consent. 3. Dementia due to probable or possible AD as defined by NIA-AA criteria. 4. 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. 5. Availability of a support person to accompany the participant to study appointments and provide collateral information as needed. 6. If taking medication for neuropsychiatric symptoms, the dose should be stable for at least 1 week. Exclusion: 1. Psychiatric diagnosis other than dementia significantly impacting the presentation. 2. Presence of delirium or other acute medical condition significantly contributing to agitation/aggression or making the study participation unsafe for a participant. 3. Any contraindication to TMS or tDCS. 4. Any other condition that in the opinion of principal investigator will make the study participation unsafe or non-feasible for the participant. 5. Currently taking anticonvulsants or benzodiazepines at a dose sufficient to cause interference with TMS-EEG. Participants with AD without aggression 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 Inclusion: 1. Age 50 years or older. 2. Able and willing to provide informed consent. 3. Free from any significant neurological disorder. Exclusion: 1. Lifetime DSM-5 diagnosis other than simple phobias or adjustment disorder. 2. Any Contraindication to TMS. 3. Currently taking anticonvulsants or benzodiazepines at a dose sufficient to cause interference with TMS-EEG. |
Country | Name | City | State |
---|---|---|---|
Canada | Centre for Addiction and Mental Health | Toronto | Ontario |
Lead Sponsor | Collaborator |
---|---|
Centre for Addiction and Mental Health | BrightFocus Foundation |
Canada,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | 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). | Baseline | |
Secondary | 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. | Approximately 2 weeks after baseline | |
Secondary | 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. | Approximately 2 weeks after baseline | |
Secondary | 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. | Approximately 2 and 4 weeks after baseline | |
Secondary | 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). | Approximately 2 and 4 weeks after baseline | |
Secondary | 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. | Approximately 2 and 4 weeks after baseline | |
Secondary | 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). | Baseline | |
Secondary | 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). | Baseline | |
Secondary | 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). | Baseline |
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