Electroconvulsive Therapy (ECT) for Agitation in Dementia (AD)

Study Overview
=================
Brief Summary
-----------------
This study will explore the effect of ECT treatments plus usual care (ECT+UC) in reducing severe agitation in patients with moderate to severe dementia including Alzheimer's Disease, Vascular dementia, Frontotemporal dementia, and Dementia with Lewy Bodies. The study will also determine the tolerability/safety outcomes of ECT+UC.

Detailed Description
-----------------
This study will be a single-arm, unblinded, non-randomized trial to determine the effect and safety of ECT for severe agitation in moderate to severe stage dementia, while also examining the durability of the acute treatment effect in an exploratory maintenance naturalistic design. We plan to enroll 50 participants with an estimated dropout rate of 20%. We expect 50 participants to complete at least 1 ECT treatment before moving into the 12-month naturalistic follow-up phase.

Official Title
-----------------
Effect and Safety of Electroconvulsive Therapy Plus Usual Care for the Acute Management of Severe Agitation in Dementia

Conditions
-----------------
Alzheimer Dementia, Agitation,Psychomotor

Intervention / Treatment
-----------------
* Device: Electroconvulsive Therapy (ECT)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Diagnosis of Dementia, of the following subtypes, Alzheimer's dementia, according to NIA-AA Criteria for dementia Vascular dementia based on: i. History consistent with insidious onset of illness and gradual clinical decline ii. MRI evidence of microvascular ischemic disease (microinfarcts) iii. Physical and neurological examination do not indicate current or prior stroke c. Frontotemporal dementia d. Dementia with Lewy Bodies Mini Mental Status Exam (MMSE) less than or equal to 15 Cohen-Mansfield Agitation Inventory Nursing Home Version (CMAI) score of 5 or more on at least one item or score of 4 on two items of aggression or physical nonaggression that holds potentially dangerous consequences including hitting (including self), kicking, grabbing onto people, pushing, throwing things, biting, scratching, spitting, hurting self or other, tearing things or destroying property, making physical sexual advances, trying to get to a different place, or intentional falling (items 1-11, 14, 15) OR one score of 5 or more in items of verbal aggression including screaming, making verbal sexual advances, and cursing or verbal aggression (items 22-24). At least one failed pharmacological intervention to manage behavioral symptoms Medically stable for safe administration of ECT verified by standard physical examination, urinalysis and serum chemistries and brain imaging when clinically indicated Comprehension of English language Authorized legal representative able and willing to give informed consent Age 40 and above Exclusion Criteria: Current diagnosis of co-morbid delirium, measured by the Confusion Assessment Measure (CAM) and by clinical diagnosis Diagnosis of vascular dementia due to stroke, based on: History consistent with abrupt onset and step-wise progression of cognitive and functional decline MRI scan within the past 12 months demonstrating evidence of hemorrhagic and embolic stroke Physical and neurologic examination consistent with current or prior stroke Lifetime or current diagnosis of Schizophrenia, Bipolar Disorder or Schizoaffective Disorder Active substance use disorder within past 6 months Treatment with ECT or other neurostimulation therapies (e.g., TMS or vagal nerve stimulation) within the past 3 months

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 130 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ECT+UC group<br> | Device: Electroconvulsive Therapy (ECT)<br>* Stimulus method of delivery will be RUL electrode placement, and ultra-brief (UB) pulse width (0.25-0.37ms). At the first ECT session, seizure threshold (ST) will be determined by titration with the empirical dose titration method and subsequent treatments will be approximately 6 times the ST. Following other NIMH sponsored multicenter ECT studies (PRIDE, U01 MH055495), stimulus settings will be adjusted as needed during the ECT course based on seizure quality and treatment efficacy. Participants will be administered anesthesia.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CMAI total score | The CMAI measures the efficacy of ECT+UC in reducing severe agitation in AD subjects. The CMAI is a 29-item scale with each item ranging from 1-7 in frequency with 7 being the highest and therefore worst outcome. | The CMAI will be collected through study completion, about 13 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Scale (ADCS-CGIC) | The ADCS-CGIC gives a discrete score that ranges from 1-7 with 7 being the worst outcome. | The ADCS-CGIC will be collected for one month | 
| Neuropsychiatric Inventory, Clinician Version (NPI-C) | The NPI-C is an improved version of the NPI composed of several domains of which we will use Agitation and Aggression, as well as their sum. The higher the frequency and/or severity within each domain, the worse the condition of the patient. | The NPI-C will be collected for one month | 
| Pittsburgh Agitation Scale (PAS) | The PAS assesses four behavioral domains. Each domain has an intensity score ranging from 0-4 with 4 being the worst outcome. | The PAS will be collected for one month | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ECT, Agitation, Alzheimer's, Dementia