RAFT-ECT: The RAFT ECT Study
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Study Design
Arms and Interventions
| 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.
|
Outcome Measures
Primary Outcome Measures
- Change in Depressive Symptoms as Assessed by Hamilton Rating Scale for Depression-17 [From baseline to end of randomized acute treatment (typically 4 weeks)]
The Hamilton Rating Scale for Depression-17 has a range of 0-52. Lower scores represent mild depression to no depression at all.
Secondary Outcome Measures
- Change in Depressive Symptoms as Assessed by Hamilton Rating Scale for Depression-17 [From end of acute ECT treatment up to 24-week follow-up]
The Hamilton Rating Scale for Depression-17 has a range of 0-52. Lower scores represent mild depression to no depression at all.
- Autobiographical Memory Interview-Short Form (AMI-SF) Consistency Scores [From Baseline to end of randomized acute treatment (typically 4 weeks)]
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.
- Clinical Global Impression-Severity (CGI-S) [From baseline to end of randomized acute treatment (typically 4 weeks)]
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.
- Clinical Global Impression-Improvement (CGI-I) [Through the randomised acute ECT treatment period (typically 4 weeks)]
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).
- Suicidality score [From baseline to end of randomized acute treatment (typically 4 weeks)]
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
- Post ECT reorientation time [After ECT sessions 3 and 6, which typically occur at the end of week 1 and week 2 in the randomised acute treatment phase.]
Post ECT reorientation time is the time taken to recover orientation immediately after ECT in randomised treatment phase.
- Change in mean neuropsychological function [From baseline to end of randomized acute treatment (typically 4 weeks)]
Assessed by a cognitive test battery.
- Mental Health Questionnaire-14 (MHQ-14) [From baseline to end of randomized acute treatment (typically 4 weeks)]
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.
- Number of responders [From baseline to End of Randomized Acute Treatment (typically 4 weeks)]
Response is defined as a 50 percent reduction in depression severity from baseline, assessed using the Hamilton Rating Scale for Depression-17
- Number of remitters [From baseline to end of randomized acute treatment (typically 4 weeks)]
Remission is defined as a score of ≤ 7 on the Hamilton Rating Scale for Depression-17.
- Number of participants switched from randomised treatment to another form of acute ECT [After at least 8 randomised ECT treatments (typically after 3 weeks).]
Number of participants switched from randomised treatment to another form of acute ECT after receiving at least 8 randomised ECT.
- Occurrence of adverse events and serious adverse events [From baseline and up to 24-week follow-up]
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).
Eligibility Criteria
Criteria
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)
-
Montreal Cognitive Assessment Battery (MoCA) score of at least 23
-
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) in the past 6 months, 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 or is currently active, 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
-
Received ECT during the past 3 months, as determined by treatment history
-
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Medical College of Georgia, Augusta University | Augusta | Georgia | United States | 30912 |
| 2 | Medical University of South Carolina | Charleston | South Carolina | United States | 29425 |
| 3 | Ramsay Clinic Northside | Sydney | New South Wales | Australia | 2065 |
| 4 | Ramsay Clinic Lakeside | Warners Bay | New South Wales | Australia | 2282 |
| 5 | Gold Coast University Hospital (GCUH) | Gold Coast | Queensland | Australia | 4215 |
| 6 | Ramsay Clinic Albert Road | Melbourne | Victoria | Australia | 3004 |
Sponsors and Collaborators
- The George Institute
- National Health and Medical Research Council, Australia
- Ramsay Clinic Albert Road, Australia
- Ramsay Clinic Lakeside, Australia
- Ramsay Clinic Northside, Australia
- Gold Coast Hospital and Health Service
- Augusta University
- Medical University of South Carolina
- The University of New South Wales
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 Documents (Full-Text)
None provided.More Information
Publications
None provided.- X22-0018
- APP1159769
- RG180233