The RAFT ECT Study

Major Depressive Episode Clinical Trial

— RAFT-ECT  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05402657
• Other study ID #: X22-0018
• Secondary ID: APP1159769RG1802
• Status: Recruiting
• Phase: N/A
• Start date: March 22, 2023
• Est. completion date: July 2025

Study information

• Verified date: October 2023
• Source: The George Institute
• Contact: Rita Barreiros
• Phone: +61 2 9065 9107
• Email: raft-ect.study[@]unsw.edu.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 154
• Est. completion date: July 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Major Depressive Episode

Intervention

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.
• 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.

Locations

Country	Name	City	State
Australia	Gold Coast University Hospital (GCUH)	Gold Coast	Queensland
Australia	Ramsay Clinic Albert Road	Melbourne	Victoria
Australia	Ramsay Clinic Northside	Sydney	New South Wales
Australia	Ramsay Clinic Lakeside	Warners Bay	New South Wales
United States	Medical College of Georgia, Augusta University	Augusta	Georgia
United States	Medical University of South Carolina	Charleston	South Carolina

Sponsors (9)

Lead Sponsor	Collaborator
The George Institute	Augusta University, Gold Coast Hospital and Health Service, Medical University of South Carolina, National Health and Medical Research Council, Australia, Ramsay Clinic Albert Road, Australia, Ramsay Clinic Lakeside, Australia, Ramsay Clinic Northside, Australia, The University of New South Wales

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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.
Secondary	Change in mean neuropsychological function	Assessed by a cognitive test battery.	From baseline to end of randomized acute treatment (typically 4 weeks)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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).
Secondary	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)
Secondary	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