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Electroconvulsive Therapy (ECT) for Agitation in Alzheimer's Dementia (AD) (ECT-AD)

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ClinicalTrials.gov Identifier: NCT03926520
Recruitment Status : Recruiting
First Posted : April 24, 2019
Last Update Posted : April 1, 2021
Sponsor:
Collaborators:
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

Tracking Information
First Submitted Date  ICMJE April 19, 2019
First Posted Date  ICMJE April 24, 2019
Last Update Posted Date April 1, 2021
Actual Study Start Date  ICMJE January 28, 2021
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 23, 2019)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 29, 2021)
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 23, 2019)
  • Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Scale (ADCS-CGIC) [ Time Frame: The ADCS-CGIC will be collected through study completion, about 13 months ]
    The ADCS-CGIC gives a discrete score that ranges from 1-7 with 7 being the worst outcome.
  • Neuropsychiatric Inventory (NPI) [ Time Frame: The NPI will be collected for one month ]
    The NPI is composed of several domains in which subscores on frequency and severity will be derived. The higher the frequency and/or severity within each domain, the worse the condition of the patient.
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Electroconvulsive Therapy (ECT) for Agitation in Alzheimer's Dementia (AD)
Official Title  ICMJE A Randomized Controlled Trial of Electroconvulsive Therapy Plus Usual Care Versus Simulated-ECT Plus Usual Care for the Acute Management of Severe Agitation in Alzheimer's Dementia
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 Alzheimer's Disease. The study will also determine the tolerability/safety outcomes of ECT+UC relative to S-ECT+UC.
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 moderate to severe stage Alzheimer's Disease (AD), 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 AD. 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 AD 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Alzheimer Dementia
  • Agitation,Psychomotor
Intervention  ICMJE
  • 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.
  • 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.
Study Arms  ICMJE
  • Experimental: ECT+UC group
    Intervention: Device: Electroconvulsive Therapy (ECT)
  • Sham Comparator: S-ECT+UC group
    Intervention: Other: Simulated Electroconvulsive Therapy (S-ECT)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 23, 2019)
200
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2023
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Diagnosis of Alzheimer's Dementia according to NIA-AA Criteria for dementia
  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 Non-AD Dementia
  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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 55 Years to 89 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Hannah L Heintz, BA 617-855-3225 hheintz@mclean.harvard.edu
Contact: Aniqa T Rahman, BA 617-855-3257 arahman@mclean.harvard.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03926520
Other Study ID Numbers  ICMJE 2020P002276
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Brent Forester, Mclean Hospital
Study Sponsor  ICMJE Brent Forester
Collaborators  ICMJE
  • Mayo Clinic
  • Pine Rest Christian Mental Health Services
  • Emory University
  • The Zucker Hillside Hospital
  • Medical University of South Carolina
Investigators  ICMJE
Principal Investigator: Brent P Forester, MD, MSc Mclean Hospital
Principal Investigator: George Petrides, MD Northwell Health
PRS Account Mclean Hospital
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP