Clinical trial NCT05402657: The RAFT ECT Study
Official title: The Randomised Controlled Trial of Frontoparietal and Temporoparietal Electroconvulsive Therapy (ECT) for Severe Depression: The RAFT ECT Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Major Depressive Episode
Keywords: Severe depression
Depressive Disorder, Treatment-Resistant
Depressive Disorder, Major
Memory
Electroconvulsive therapy
Randomised clinical trial
Lead sponsor: The George Institute
Sponsor class: OTHER
Collaborators: name: National Health and Medical Research Council, Australia
name: Ramsay Clinic Albert Road, Australia
name: Ramsay Clinic Lakeside, Australia
name: Ramsay Clinic Northside, Australia
name: Gold Coast Hospital and Health Service
name: Augusta University
name: Medical University of South Carolina
name: The University of New South Wales
name: Emory University
First posted: 2022-06-02
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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)
* 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
* 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.

Primary outcomes:
measure: Change in Depressive Symptoms as Assessed by Hamilton Rating Scale for Depression-17
timeFrame: From baseline to end of randomized acute treatment (typically 4 weeks)
Secondary outcomes:
measure: Change in Depressive Symptoms as Assessed by Hamilton Rating Scale for Depression-17
timeFrame: From end of acute ECT treatment up to 24-week follow-up
measure: Autobiographical Memory Interview-Short Form (AMI-SF) Consistency Scores
timeFrame: From Baseline to end of randomized acute treatment (typically 4 weeks)
measure: Clinical Global Impression-Severity (CGI-S)
timeFrame: From baseline to end of randomized acute treatment (typically 4 weeks)
measure: Clinical Global Impression-Improvement (CGI-I)
timeFrame: Through the randomized acute ECT treatment period (typically 4 weeks)
measure: Suicidality score
timeFrame: From baseline to end of randomized acute treatment (typically 4 weeks)
measure: Post ECT reorientation time
timeFrame: After ECT sessions 3 and 6, which typically occur at the end of week 1 and week 2 in the randomised acute treatment phase.
measure: Change in mean neuropsychological function
timeFrame: From baseline to end of randomized acute treatment (typically 4 weeks)
measure: Mental Health Questionnaire-14 (MHQ-14)
timeFrame: From baseline to end of randomized acute treatment (typically 4 weeks)
measure: Number of responders
timeFrame: From baseline to End of Randomized Acute Treatment (typically 4 weeks)
measure: Number of remitters
timeFrame: From baseline to end of randomized acute treatment (typically 4 weeks)
measure: Number of participants switched from randomized treatment to another form of acute ECT
timeFrame: After at least 8 randomized ECT treatments (typically after 3 weeks).
measure: Number of randomized ECT treatments given over the Acute Study Treatment Phase (RCT)
timeFrame: From baseline to End of Randomized Acute Treatment (typically 4 weeks)
measure: Occurrence of adverse events and serious adverse events
timeFrame: From baseline and up to 24-week follow-up
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Augusta
country: United States
facility: Medical College of Georgia, Augusta University
state: Georgia
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Sydney
country: Australia
facility: Ramsay Clinic Northside
state: New South Wales
city: Warners Bay
country: Australia
facility: Ramsay Clinic Lakeside
state: New South Wales
city: Gold Coast
country: Australia
facility: Gold Coast University Hospital (GCUH)
state: Queensland
city: Melbourne
country: Australia
facility: Ramsay Clinic Albert Road
state: Victoria
Study officials:
affiliation: University of New South Wales
name: Colleen Loo
role: PRINCIPAL_INVESTIGATOR
affiliation: The George Institute
name: Anthony Rodgers
role: STUDY_DIRECTOR
References: