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Enhancing the Effectiveness of Electroconvulsive Therapy in Severe Depression (EFFECT-Dep)

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ClinicalTrials.gov Identifier: NCT01907217
Recruitment Status : Completed
First Posted : July 24, 2013
Results First Posted : November 14, 2018
Last Update Posted : November 14, 2018
Sponsor:
Collaborator:
Health Research Board, Ireland
Information provided by (Responsible Party):
Prof Declan McLoughlin, St Patrick's Hospital, Ireland

Tracking Information
First Submitted Date  ICMJE June 16, 2013
First Posted Date  ICMJE July 24, 2013
Results First Submitted Date  ICMJE December 21, 2016
Results First Posted Date  ICMJE November 14, 2018
Last Update Posted Date November 14, 2018
Study Start Date  ICMJE May 2008
Actual Primary Completion Date November 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 22, 2018)
Hamilton Depression Rating Scale (HDRS) [ Time Frame: HDRS scores were obtained at baseline, end of allocated ECT treatment, and at 3 and 6 month follow-up timepoints. ]
The HDRS was originally designed to assess severity of depressive symptoms in patients with a primary depressive illness and is now the most commonly used measure of depression severity. It was first published in a 17-item format with the optional addition of 4 items making up the 21-item version. In addition to the original 21 items, the 24-item HDRS includes items on helplessness, hopelessness and worthlessness; its score range is 0-77, with higher scores reflecting greater burden of depressive symptoms.
Original Primary Outcome Measures  ICMJE
 (submitted: July 18, 2013)
Change from baseline in Hamilton Depression Rating Scale (HDRS) [ Time Frame: Change from baseline (pre randomisation) in HDRS at end of the ECT course, up to a maximum 12 ECT sessions twice weekly over 6 weeks. Mean number of sessions is 8, taking 4 weeks. Comparisons of HDRS scores at further timepoints are secondary outcomes. ]
The HDRS was originally designed to assess severity of depressive symptoms in patients with a primary depressive illness and is now the most commonly used measure of depression severity. It was first published in a 17-item format with the optional addition of 4 items making up the 21-item version. In addition to the original 21 items, the 24-item HDRS includes items on helplessness, hopelessness and worthlessness.
Change History Complete list of historical versions of study NCT01907217 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 22, 2018)
  • Columbia Autobiographical Memory Interview-Short Form (AMI-SF) [ Time Frame: end of allocated ECT course ]
    The AMI-SF is used to assess retrospective autobiographical memory function. It has six categories, which involve five questions each, about a family member, most recent travel, last New Year's Eve, last birthday, most recent employment and last visit to a doctor for a physical complaint. At baseline interviewers encourage the participant to recall as much information as they can. Responses at baseline can be scored either two points, for a recognisable real memory, or zero for no memory or too little information to constitute a proper memory. Only those questions for which a memory had been retrieved at baseline are examined at follow-up. Follow-up assessments are scored as percentage recall of baseline score, which is scored as 100% irrespective of actual performance..
  • Columbia Autobiographical Memory Interview-Short Form (AMI-SF) [ Time Frame: 3 months follow-up ]
    The AMI-SF is used to assess retrospective autobiographical memory function. It has six categories, which involve five questions each, about a family member, most recent travel, last New Year's Eve, last birthday, most recent employment and last visit to a doctor for a physical complaint. At baseline interviewers encourage the participant to recall as much information as they can. Responses at baseline can be scored either two points, for a recognisable real memory, or zero for no memory or too little information to constitute a proper memory. Only those questions for which a memory had been retrieved at baseline are examined at follow-up. Follow-up assessments are scored as percentage recall of baseline score, which is scored as 100% irrespective of actual performance..
  • Columbia Autobiographical Memory Interview-Short Form (AMI-SF) [ Time Frame: 6 months follow-up ]
    The AMI-SF is used to assess retrospective autobiographical memory function. It has six categories, which involve five questions each, about a family member, most recent travel, last New Year's Eve, last birthday, most recent employment and last visit to a doctor for a physical complaint. At baseline interviewers encourage the participant to recall as much information as they can. Responses at baseline can be scored either two points, for a recognisable real memory, or zero for no memory or too little information to constitute a proper memory. Only those questions for which a memory had been retrieved at baseline are examined at follow-up. Follow-up assessments are scored as percentage recall of baseline score, which is scored as 100% irrespective of actual performance..
Original Secondary Outcome Measures  ICMJE
 (submitted: July 18, 2013)
  • Change from baseline in Hamilton Depression Rating Scale (HDRS) [ Time Frame: Change from baseline (pre randomisation) in HDRS at 3 months after completion of allocated ECT course. ]
    The HDRS was originally designed to assess severity of depressive symptoms in patients with a primary depressive illness and is now the most commonly used measure of depression severity. It was first published in a 17-item format with the optional addition of 4 items making up the 21-item version. In addition to the original 21 items, the 24-item HDRS includes items on helplessness, hopelessness and worthlessness.
  • Change from baseline in Hamilton Depression Rating Scale (HDRS) [ Time Frame: Change from baseline (pre randomisation) in HDRS at 6 months after completion of allocated ECT course. ]
    The HDRS was originally designed to assess severity of depressive symptoms in patients with a primary depressive illness and is now the most commonly used measure of depression severity. It was first published in a 17-item format with the optional addition of 4 items making up the 21-item version. In addition to the original 21 items, the 24-item HDRS includes items on helplessness, hopelessness and worthlessness.
  • Change from baseline in Hamilton Depression Rating Scale (HDRS) [ Time Frame: Change from baseline (pre randomisation) in HDRS at 9 months after completion of allocated ECT course. ]
    The HDRS was originally designed to assess severity of depressive symptoms in patients with a primary depressive illness and is now the most commonly used measure of depression severity. It was first published in a 17-item format with the optional addition of 4 items making up the 21-item version. In addition to the original 21 items, the 24-item HDRS includes items on helplessness, hopelessness and worthlessness.
  • Change from baseline in Hamilton Depression Rating Scale (HDRS) [ Time Frame: Change from baseline (pre randomisation) in HDRS at 12 months after completion of allocated ECT course. ]
    The HDRS was originally designed to assess severity of depressive symptoms in patients with a primary depressive illness and is now the most commonly used measure of depression severity. It was first published in a 17-item format with the optional addition of 4 items making up the 21-item version. In addition to the original 21 items, the 24-item HDRS includes items on helplessness, hopelessness and worthlessness.
  • Columbia Autobiographical Memory Interview-Short Form (AMI-SF) [ Time Frame: Baseline (pre randomisation); end of allocated ECT course; 3 months; 6 months; 9 months; and 12 months after end of allocated ECT course. ]
    The AMI-SF is used to assess retrospective autobiographical memory function. It has six categories, which involve five questions each, about a family member, most recent travel, last New Year's Eve, last birthday, most recent employment and last visit to a doctor for a physical complaint. At baseline interviewers encourage the participant to recall as much information as they can. Responses at baseline can be scored either two points, for a recognisable real memory, or zero for no memory or too little information to constitute a proper memory. Only those questions for which a memory had been retrieved at baseline are examined at follow-up. Follow-up assessments are scored as percentage recall of baseline score.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: July 18, 2013)
other neuropsychology tests [ Time Frame: Baseline (pre randomisation); end of allocated ECT course; 3 months; 6 months; 9 months; and 12 months after end of allocated ECT course. ]
General cognition will be assessed using the Addenbrooke's Cognitive Examination-revised version(ACE-R).
  • recovery of orientation after ECT sessions
  • retrograde amnesia for impersonal memory will be assessed, using a 60-item multiple choice Public Events Questionnaire
  • Forward and Backward Digit Spans: immediate short-term memory plus attention and working memory
  • Trail Making Test (Part A): motor and psychomotor speed
  • Grooved Pegboard Test: speeded fine eye-hand coordination
  • Trail Making Test (Part B) plus letter and category verbal fluencies: frontal/executive function
  • Anterograde verbal and visual memory will be tested, respectively, using the Free and Cued Selective Reminding Test (immediate and delayed recall) and Complex Figures Test (immediate and delayed recall; different figures for repeat testing).
Where possible, parallel versions will be used when appropriate to reduce practice effects.
 
Descriptive Information
Brief Title  ICMJE Enhancing the Effectiveness of Electroconvulsive Therapy in Severe Depression
Official Title  ICMJE A Randomised Controlled Trial of Standard Bilateral Electroconvulsive Therapy Versus High-dose Unilateral Electroconvulsive Therapy for Severe Depression
Brief Summary

Electroconvulsive therapy (ECT) is the most powerful antidepressant treatment available and is often life-saving. There are concerns, however, that standard bitemporal ECT (the most commonly used form of ECT worldwide) causes persisting retrograde amnesia. However, clinical trials have indicated that high-dose unilateral ECT may be as effective as bitemporal ECT but have much less cognitive side-effects.

The trial aims to test the primary experimental hypothesis: High-dose (6 x ST) right unilateral ECT is as effective as (i.e. not inferior to) standard (1.5 x ST) bitemporal ECT for severe depression in terms of Hamilton Depression Rating Score (HDRS) at the end of the treatment course.

Detailed Description

The study is a two-group parallel design randomised controlled non-inferiority trial and has been registered (ISRCTN23577151). Consented patients with major depressive disorder (DSM-IV) will be randomly allocated to a course of bitemporal (BT) ECT (1.5 x ST) or high-dose right unilateral (RUL) ECT (6.0 x ST). To facilitate generalizability of results, the trial takes place under "real world" conditions and so both groups continue usual care and medications during the treatment phase and thereafter. Patients are followed-up for 12 months after completing their allocated course of ECT. Completion of the primary outcome depression-rating measure (i.e. HDRS) and the secondary outcome of most interest (autobiographical memory, using the AMI-SF) will be prioritised in the data collection.

Patients, their treating clinicians and raters are blind to treatment; clinicians administering ECT are not involved in post randomisation assessments or formal data analysis. Success of blinding for patients and raters will be assessed after the second and final treatments. The trial statistician is also blinded to allocation status.

Sample size: In a large series (n = 253) of depressed patients, Petrides et al. (2001) found a mean (SD) reduction in 24-item HDRS of 25.6 (9.4) after treatment with bitemporalT ECT (1.5 x ST). We therefore estimate that 69 patients will be required per treatment group to have 80% power to demonstrate, using a one-sided equivalence t-test at 5% level, that mean reduction in 24-item HDRS achieved using high-dose RUL ECT is no more than 4 points (i.e. equivalent to 3 points on 17-item HDRS) less than that achieved using standard BT ECT, assuming a common within-group SD of change scores of 9.4 and equal expected group mean change scores.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Depression
Intervention  ICMJE
  • Device: ECT Mecta 5000M
    ECT is administered twice weekly with hand-held electrodes using the Mecta 5000M device following a standard stimulus dosing protocol. Seizure duration is measured by EEG monitoring. Methohexitone (0.75-1.0 mg/kg) is used for anaesthesia with suxamethonium (0.5-1.0 mg/kg) as muscle relaxant. Seizure threshold (ST) is established by a method of limits at the first session and subsequent treatments will be given at 1.5 x ST for BT ECT and 6.0 x ST for RUL ECT. To reflect routine clinical practice, number of ECT treatments is determined by referring physicians who will be blind to randomisation. The treatment period varies between patients to allow up to 12 administrations of ECT, i.e. up to 6 weeks.
    Other Name: electroconvulsive therapy Mecta 500M device
  • Drug: Methohexitone
    Methohexitone (0.75-1.0 mg/kg) is used for anaesthesia along with suxamethonium (0.5-1.0 mg/kg)for muscle relaxation. Anesthesia is the same for both arms of the trial.
    Other Names:
    • methohexital
    • Brevimytal (Hikma, Germany)
  • Drug: Suxamethonium
    Suxamethonium (0.5-1.0 mg/kg)is used for muscle relaxation along with Methohexitone (0.75-1.0 mg/kg) for anaesthesia. Anesthesia is the same for both arms of the trial.
    Other Names:
    • Succinylcholine
    • Anectine (GlaxoSmithKline, UK)
Study Arms  ICMJE
  • Active Comparator: Bilateral ECT Mecta 5000M
    Modified bilateral ECT (bitemporal electrode positions) twice weekly at 1.5 times the seizure threshold. Methohexitone (0.75-1.0 mg/kg) is used for anaesthesia with suxamethonium (0.5-1.0mg/kg) for muscle relaxation.
    Interventions:
    • Device: ECT Mecta 5000M
    • Drug: Methohexitone
    • Drug: Suxamethonium
  • Experimental: High-dose unilateral ECT Mecta 5000M
    High-dose right modified unilateral ECT twice weekly at 6 times the seizure threshold. Methohexitone (0.75-1.0 mg/kg) is used for anaesthesia with suxamethonium (0.5-1.0mg/kg) for muscle relaxation.
    Interventions:
    • Device: ECT Mecta 5000M
    • Drug: Methohexitone
    • Drug: Suxamethonium
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 Completed
Actual Enrollment  ICMJE
 (submitted: July 18, 2013)
138
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE April 2015
Actual Primary Completion Date November 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients ≥18 years diagnosed with major depressive episode (DSM-IV) and referred for ECT

Exclusion Criteria:

  • Any condition rendering patients medically unfit for general anaesthesia or ECT; treatment with ECT in previous six months; dementia or other Axis 1 diagnosis; alcohol/other substance abuse in previous six months; inability/refusal to consent.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Ireland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01907217
Other Study ID Numbers  ICMJE TRA/2007/5
ISRCTN23577151 ( Registry Identifier: Current Controlled Trials )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description: We are continuing to analyze trial data for secondary analyses. Requests for IPD will be considered where appropriate.
Responsible Party Prof Declan McLoughlin, St Patrick's Hospital, Ireland
Study Sponsor  ICMJE St Patrick's Hospital, Ireland
Collaborators  ICMJE Health Research Board, Ireland
Investigators  ICMJE
Principal Investigator: Declan M McLoughlin, PhD St Patrick's University Hospital
PRS Account St Patrick's Hospital, Ireland
Verification Date April 2018

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