The RAFT ECT Study (RAFT-ECT)

The Randomised Controlled Trial of Frontoparietal and Temporoparietal Electroconvulsive Therapy (ECT) for Severe Depression: The RAFT ECT Study

Severe depression is devastating for those affected and is often associated with significant risk of suicide. Electroconvulsive therapy (ECT) is a highly effective acute treatment for severe depression, but its use and acceptability are limited by cognitive side effects. Of these, retrograde memory loss is most concerning, and can be long-term. The introduction of ultrabrief right unilateral (UBRUL) ECT into clinical practice has been an important step in reducing the risk of memory impairment, but significant deficits still occur.

A new form of UBRUL ECT which utilises a Frontoparietal electrode placement represents a further development. Preliminary data suggest that Frontoparietal UBRUL has good efficacy and less cognitive side effects than UBRUL given using the conventional Temporoparietal electrode placement. Designed as a pivotal trial, this protocol will be the first RCT comparing these two forms of ECT, producing the rigorous efficacy and safety data required to change clinical practice/policy.

This is a multicentre, parallel group RCT with 1:1 allocation ratio between Frontoparietal (intervention) and Temporoparietal (comparator) forms of UBRUL ECT. Participation will involve receiving randomised acute ECT under blinded conditions during the randomised acute treatment period (typically around 4 weeks), then completion of a 24-week follow-up period which commences after the cessation of all acute ECT. The study protocol aims to provide 12 randomised acute ECT treatments, though the number of treatments (and hence the length of the randomised acute treatment period) can be adjusted by the participant's own treating/admitting psychiatrist according to their clinical judgement.

Study Overview

• Status: Recruiting
• Conditions: Major Depressive Episode
• Intervention / Treatment: Procedure: Frontoparietal Ultrabrief Right Unilateral (UBRUL-FP) electroconvulsive therapy; Procedure: Temporoparietal Ultrabrief Right Unilateral (UBRUL-TP) electroconvulsive therapy

• Study Type: Interventional
• Enrollment (Estimated): 154
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rita Barreiros; Phone Number: +61 2 9065 9107; Email: raft-ect.study@unsw.edu.au
• Study Contact Backup: Name: Louise Brettell; Email: raft-ect.study@unsw.edu.au

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2065
      • Recruiting
      • Ramsay Clinic Northside
      • Contact: Colleen Loo; Phone Number: +61 2 9433 3555; Email: researchstudies.ns@ramsayhealth.com.au
    • Warners Bay, New South Wales, Australia, 2282
      • Recruiting
      • Ramsay Clinic Lakeside
      • Contact: Shane Hansen; Phone Number: +61 2 4941 3707; Email: RAFTStudy.WBP@ramsayhealth.com.au
  • Queensland
    • Gold Coast, Queensland, Australia, 4215
      • Recruiting
      • Gold Coast University Hospital (GCUH)
      • Contact: Shanthi Sarma; Phone Number: 1300 744 284; Email: Shanthi.Sarma@health.qld.gov.au
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • Ramsay Clinic Albert Road
      • Contact: Melanie Hurley; Phone Number: +61 3 9279 3569; Email: Research.ARC@ramsayhealth.com.au
• United States
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Recruiting
      • Medical College of Georgia, Augusta University
      • Contact: Laryssa McCloud; Phone Number: 706-721-7968; Email: lmccloud@augusta.edu
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina
      • Contact: Morgan Dancy; Phone Number: 843-876-5141; Email: maddoxm@musc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• DSM-5 diagnosis* of major depressive episode (unipolar or bipolar)
• HRSD-17 score ≥ 17 at Screening
• At least 18 years old
• Able to tolerate washout of prohibited medications and restriction on benzodiazepine dosage, as determined by patient's own treating psychiatrist.
• ECT indicated for treatment of depression, as determined by own treating referring psychiatrist and confirmed by research evaluations (e.g., diagnosis of depression)
• Willing and able to participate in research and comply with study requirements
• Sufficient proficiency in spoken English to ensure validity of neuropsychological testing (e.g., worked or studied in an English-speaking context or equivalent)

Exclusion Criteria:

• History of schizophrenia, schizoaffective disorder, other [non-mood disorder] psychosis, or rapid cycling bipolar disorder (DSM-5 diagnoses*)
• Current manic episode, hypomanic episode, or major depressive episode with mixed features (DSM-5 diagnoses*)
• Alcohol or substance use disorder (other than caffeine or nicotine) present in the past month, or is likely to be present during the 24-week study period as determined by study physician evaluation
• Diagnosis of amnestic disorder, dementia, delirium, or epilepsy, as determined by study physician evaluation and medical history
• Central nervous system disease or brain injury that has resulted in significant cognitive impact, as determined by study physician evaluation and medical history
• Serious or unstable medical condition, as determined by study physician evaluation and medical history
• If female of childbearing potential: a) pregnancy as determined by pregnancy urine screen, and/or b) current breastfeeding
• Completed an acute course of ECT during the past 2 months, as determined by treatment history
• Received any ECT during the past 2 weeks
• Failed an adequate course of ECT (i.e., 8 ECT treatments ) in the current depressive episode
• Patients who are prisoners, and those who lack capacity to make medical decisions (as judged by their own treating psychiatrist)
• Currently enrolled in another interventional clinical trial

• Currently using another investigational device or product

  • DSM-5 psychiatric diagnoses will be assessed and confirmed using the Mini International Neuropsychiatric Interview (MINI; Sheehan et al., 1998) Version 7.0.2 for DSM-5, administered by research team members.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Frontoparietal ECT Group; Participants will receive ultrabrief right unilateral ECT with a frontoparietal placement of ECT electrodes.	Procedure: Frontoparietal Ultrabrief Right Unilateral (UBRUL-FP) electroconvulsive therapy; UBRUL-FP involves ultrabrief right unilateral ECT delivered using a novel frontoparietal montage, where the anterior electrode is shifted frontally to a position above the midpoint of the right eye to avoid temporal lobe stimulation (and reduce memory side effects). UBRUL-FP will be delivered using standard ECT devices.
Active Comparator: Temporoparietal ECT Group; Participants will receive ultrabrief right unilateral ECT with the conventional temporoparietal placement of ECT electrodes.	Procedure: Temporoparietal Ultrabrief Right Unilateral (UBRUL-TP) electroconvulsive therapy; UBRUL-TP is the standard form of ultrabrief right unilateral ECT, using the conventional temporoparietal (d'Elia) electrode placement, where the anterior electrode is placed over the right temporal lobe. UBRUL-TP will be delivered using standard ECT devices.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Depressive Symptoms as Assessed by Hamilton Rating Scale for Depression-17	The Hamilton Rating Scale for Depression-17 has a range of 0-52. Lower scores represent mild depression to no depression at all.	From baseline to end of randomized acute treatment (typically 4 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Depressive Symptoms as Assessed by Hamilton Rating Scale for Depression-17	The Hamilton Rating Scale for Depression-17 has a range of 0-52. Lower scores represent mild depression to no depression at all.	From end of acute ECT treatment up to 24-week follow-up
Autobiographical Memory Interview-Short Form (AMI-SF) Consistency Scores	In the Autobiographical Memory Interview-Short Form, participants are graded on the consistency of their answers between baseline and subsequent time-points. The maximum consistency score is 100 percent, with lower percentages representing increasing inconsistency in retrospective autobiographical memory function.	From Baseline to end of randomized acute treatment (typically 4 weeks)
Clinical Global Impression-Severity (CGI-S)	The Clinical Global Impression-Severity measure is a 7-point scale where a clinician rates the severity of a patient's illness in comparison to the clinician's experience with patients who have the same diagnosis. The ratings range from 1 indicating normal, not at all ill to 7 suggesting they are among the most extremely ill patients.	From baseline to end of randomized acute treatment (typically 4 weeks)
Clinical Global Impression-Improvement (CGI-I)	The Clinical Global Impression-Improvement is a measure where a clinician assesses how much the patient's illness has improved or worsened in comparison to baseline. The "improved" version being used in this trial (Kadouri, Corruble & Falissard, 2007) is a 13-point scale with ratings which range from 6 ('ideal improvement') to -6 (maximum deterioration).	Through the randomized acute ECT treatment period (typically 4 weeks)
Suicidality score	Assessed by examining scores on item 3 (suicidality) of the Hamilton Rating Scale for Depression (which range from 0 to 4, where higher scores indicate more severe and/or persistent suicidality) and scores on the suicidal ideation subscale of the Columbia	From baseline to end of randomized acute treatment (typically 4 weeks)
Post ECT reorientation time	Post ECT reorientation time is the time taken to recover orientation immediately after ECT in randomised treatment phase.	After ECT sessions 3 and 6, which typically occur at the end of week 1 and week 2 in the randomised acute treatment phase.
Change in mean neuropsychological function	Assessed by a cognitive test battery.	From baseline to end of randomized acute treatment (typically 4 weeks)
Mental Health Questionnaire-14 (MHQ-14)	The Mental Health Questionnaire-14 is a self-report quality of life instrument consisting of the mental health component of the Medical Outcomes Study questionnaire. This patient self-report measure contains 14 items in total, addressing symptoms of fatigue, anxiety and depression, and the impact of these symptoms on functioning. Scores on this measure range from 0 to 100, where higher scores indicate better quality of life.	From baseline to end of randomized acute treatment (typically 4 weeks)
Number of responders	Response is defined as a 50 percent reduction in depression severity from baseline, assessed using the Hamilton Rating Scale for Depression-17	From baseline to End of Randomized Acute Treatment (typically 4 weeks)
Number of remitters	Remission is defined as a score of ≤ 7 on the Hamilton Rating Scale for Depression-17.	From baseline to end of randomized acute treatment (typically 4 weeks)
Number of participants switched from randomized treatment to another form of acute ECT	Number of participants switched from randomized treatment to another form of acute ECT after receiving at least 8 randomized ECT.	After at least 8 randomized ECT treatments (typically after 3 weeks).
Number of randomized ECT treatments given over the Acute Study Treatment Phase (RCT)	Number of randomized acute ECT treatments received by participants during the Acute Study Treatment Phase (RCT), compared between the groups.	From baseline to End of Randomized Acute Treatment (typically 4 weeks)
Occurrence of adverse events and serious adverse events	Occurrence of adverse events (AEs) and serious adverse events (SAEs) compared between the groups, based on treating them as binary outcomes (no/yes, e.g., whether participants experienced any given side effect/adverse event at least once) and as count outcomes (number of occurrences).	From baseline and up to 24-week follow-up

Collaborators and Investigators

• Sponsor: The George Institute
• Collaborators: National Health and Medical Research Council, Australia; Medical University of South Carolina; Augusta University; Gold Coast Hospital and Health Service; The University of New South Wales; Ramsay Clinic Albert Road, Australia; Ramsay Clinic Lakeside, Australia; Ramsay Clinic Northside, Australia
• Investigators: Principal Investigator: Colleen Loo, University of New South Wales; Principal Investigator: Anthony Rodgers, The George Institute; Principal Investigator: Malcolm Hopwood, University of Melbourne; Principal Investigator: Alan Weis, Newcastle University; Principal Investigator: Shanthi Sarma, Gold Coast Hospital and Health Services; Principal Investigator: Michael Bull, Ramsay Clinic Lakeside, Warners Bay Private Hospital; Principal Investigator: Vaughn McCall, Augusta University; Principal Investigator: Mark George, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2023
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: May 5, 2022
• First Submitted That Met QC Criteria: May 30, 2022
• First Posted (Actual): June 2, 2022

Study Record Updates

• Last Update Posted (Actual): October 5, 2023
• Last Update Submitted That Met QC Criteria: October 3, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Memory; Depressive Disorder, Major; Randomised clinical trial; Electroconvulsive therapy; Depressive Disorder, Treatment-Resistant; Severe depression
• Other Study ID Numbers: X22-0018; APP1159769 (Other Grant/Funding Number: NHMRC); RG180233 (Other Identifier: UNSW project number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data will be shared upon request to the data custodian, subject to approval from the Trial Steering Committee and signing of data transfer agreements.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No