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

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ClinicalTrials.gov Identifier: NCT03926520
Recruitment Status : Recruiting
First Posted : April 24, 2019
Last Update Posted : June 15, 2022
Mayo Clinic
Pine Rest Christian Mental Health Services
Emory University
The Zucker Hillside Hospital
Medical University of South Carolina
Information provided by (Responsible Party):
Brent Forester, Mclean Hospital

Brief Summary:
This study will explore the efficacy of ECT treatments plus usual care (ECT+UC), relative to a placebo simulated ECT plus usual care (S-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 relative to S-ECT+UC.

Condition or disease Intervention/treatment Phase
Alzheimer Dementia Agitation,Psychomotor Device: Electroconvulsive Therapy (ECT) Other: Simulated Electroconvulsive Therapy (S-ECT) Not Applicable

Detailed Description:
This study is a single blind, randomized, Simulated-ECT (S-ECT) controlled trial of electroconvulsive therapy (ECT). The purpose is to determine the efficacy and safety of ECT for severe agitation in patients with moderate to severe dementia including Alzheimer's Disease, Vascular dementia, Frontotemporal dementia, and Dementia with Lewy Bodies, while also examining the durability of the acute treatment effect in an exploratory maintenance naturalistic design. The investigators will study only inpatients with severe agitation and moderate to severe dementia, associated with high care costs and poor quality of life, who typically have already failed prior trials of psychotropic medications. The first aim is to compare the relative efficacy of up to 9 ECT treatments plus usual care (ECT+UC) versus Simulated ECT (S-ECT+UC) in reducing severe agitation in 200 participants with moderate to severe dementia including Alzheimer's Disease, Vascular dementia, Frontotemporal dementia, and Dementia with Lewy Bodies. The second aim is to compare the relative tolerability/safety outcomes of ECT+UC versus S-ECT+UC in the same group of participants. The exploratory aim is to understand the stability of agitation reduction (CMAI) and global functioning (Clinical Global Impression-Severity [CGI-S]) with assessments at 1,3, and 6 months following the randomized phase, and then for a fourth visit 12 months after the randomized phase. Establishing safety and efficacy of ECT for severe agitation in dementias provides an opportunity to decrease long-term care placement, decrease the risk of mortality, decrease caregiver burden, and enhance quality of life for patients and their caregivers.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized Controlled Trial of Electroconvulsive Therapy Plus Usual Care Versus Simulated-ECT Plus Usual Care for the Acute Management of Severe Agitation in Dementia
Actual Study Start Date : January 28, 2021
Estimated Primary Completion Date : March 2024
Estimated Study Completion Date : March 2024

Arm Intervention/treatment
Experimental: ECT+UC group Device: Electroconvulsive Therapy (ECT)
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.

Sham Comparator: S-ECT+UC group Other: Simulated Electroconvulsive Therapy (S-ECT)
The participant is brought to the ECT suite for the length a session would normally take (approximately 2 hours). While in the ECT suite, conducting gel will be placed on the scalp of the S-ECT subjects to parallel the ECT procedures in the ECT active group. An IV will be placed to provide PRN medication and fluids as needed. IV placement will also provide a method for study staff to assess physical interference and subject resistance to treatment. Participants will not be administered anesthesia.

Primary Outcome Measures :
  1. CMAI total score [ Time Frame: The CMAI will be collected through study completion, about 13 months ]
    The CMAI measures the efficacy of ECT+UC in reducing severe agitation in AD subjects than S-ECT. 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.

Secondary Outcome Measures :
  1. Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Scale (ADCS-CGIC) [ Time Frame: The ADCS-CGIC will be collected for one month ]
    The ADCS-CGIC gives a discrete score that ranges from 1-7 with 7 being the worst outcome.

  2. Neuropsychiatric Inventory, Clinician Version (NPI-C) [ Time Frame: The NPI-C will be collected for one month ]
    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.

  3. Pittsburgh Agitation Scale (PAS) [ Time Frame: The PAS will be collected for one month ]
    The PAS assesses four behavioral domains. Each domain has an intensity score ranging from 0-4 with 4 being the worst outcome.

Information from the National Library of Medicine

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Ages Eligible for Study:   55 Years to 89 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Diagnosis of Dementia, of the following subtypes,

    • Alzheimer's dementia, according to NIA-AA Criteria for dementia
    • Vascular dementia based on:
    • History consistent with insidious onset of illness and gradual clinical decline
    • MRI evidence of microvascular ischemic disease (microinfarcts)
    • Physical and neurological examination do not indicate current or prior stroke
    • Frontotemporal dementia
    • Dementia with Lewy Bodies
  2. MMSE ≤ 15
  3. Cohen-Mansfield Agitation Inventory Short Version (CMAI) score of ≥5 on at least one item of aggression or a physical nonaggressive item 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, intentional falling, screaming, making verbal sexual advances, and cursing or verbal aggression (items 1-11, 14, 15, 22-24).
  4. At least three failed pharmacological interventions from different drug classes (including antidepressants, antipsychotics, anticonvulsants, prazosin, and cannabinoids) at therapeutic doses (to be determined by clinical judgment) and duration of at least two weeks each to manage behavioral symptoms. These interventions may also include medications discontinued after 1 week due to tolerability concerns. Furthermore, medication trials that occur prior to admission to the hospital may count towards the three failed trials. The trials can be inpatient and/or outpatient. These trials can also be concurrent, such as using two medications from different classes for at least one week at the same time (i.e. polypharmacy).
  5. Medically stable for safe administration of ECT verified by standard physical examination, urinalysis and serum chemistries
  6. Comprehension of English language
  7. Authorized legal representative able and willing to give informed consent
  8. Age 55 - 89 years old (inclusive)

Exclusion Criteria:

  1. Current diagnosis of co-morbid delirium, measured by the Confusion Assessment Measure (CAM) and by clinical diagnosis
  2. 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
  3. Lifetime or current diagnosis of Schizophrenia, Bipolar Disorder or Schizoaffective Disorder
  4. Active substance use disorder within past 6 months
  5. Treatment with ECT or other neurostimulation therapies (e.g., TMS or vagal nerve stimulation) within the past 3 months

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03926520

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Contact: Jefferson Mattingly, BA 617-855-3168 jmattingly@mclean.harvard.edu
Contact: Maria DelPico, BS 617-855-3168 mdelpico@mclean.harvard.edu

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United States, Georgia
Emory Healthcare Recruiting
Atlanta, Georgia, United States, 30308
Contact: Valeriya Tsygankova       valeriya.tsygankova@emory.edu   
Principal Investigator: Adriana Hermida, MD         
United States, Massachusetts
McLean Hospital Recruiting
Belmont, Massachusetts, United States, 02478
Contact: Jefferson Mattingly, BA       jmattingly@mclean.harvard.edu   
Principal Investigator: Brent P Forester, MD, MSc         
United States, Michigan
Pine Rest Christian Mental Health Services Recruiting
Grand Rapids, Michigan, United States, 49548
Contact: Olivia Holzgen       Olivia.Holzgen@pinerest.org   
Principal Investigator: Louis Nykamp, MD         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Sarah Williams       Williams.Sarah2@mayo.edu   
Principal Investigator: Maria I Lapid, MD         
United States, New York
Northwell Health Recruiting
Glen Oaks, New York, United States, 11004
Contact: Heela Azizi       hazizi@northwell.edu   
Principal Investigator: Georgios Petrides, MD         
Sponsors and Collaborators
Brent Forester
Mayo Clinic
Pine Rest Christian Mental Health Services
Emory University
The Zucker Hillside Hospital
Medical University of South Carolina
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Principal Investigator: Brent P Forester, MD, MSc Mclean Hospital
Principal Investigator: George Petrides, MD Northwell Health
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Responsible Party: Brent Forester, Principal Investigator, Mclean Hospital
ClinicalTrials.gov Identifier: NCT03926520    
Other Study ID Numbers: 2020P002276
First Posted: April 24, 2019    Key Record Dates
Last Update Posted: June 15, 2022
Last Verified: June 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Keywords provided by Brent Forester, Mclean Hospital:
Additional relevant MeSH terms:
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Alzheimer Disease
Psychomotor Agitation
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Neurodegenerative Diseases
Neurologic Manifestations
Psychomotor Disorders
Neurobehavioral Manifestations