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Trial registered on ANZCTR


Registration number
ACTRN12611000054910
Ethics application status
Approved
Date submitted
22/11/2010
Date registered
17/01/2011
Date last updated
26/11/2018
Date data sharing statement initially provided
26/11/2018
Date results information initially provided
26/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating Magnetic Seizure Therapy in Major Depressive Disorder.
Scientific title
A randomised controlled trial of Magnetic Seizure Therapy for the treatment of Major Depressive Disorder
Secondary ID [1] 253134 0
Project 363/10
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Treatment Resistant Major Depression 258693 0
Condition category
Condition code
Mental Health 258837 258837 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Magnetic Seizure Therapy (MST).

MST uses magnetic stimulation to induce a seizure for therapeutic purposes. Magnetic stimulation is a non invasive technique for stimulating neural tissue. A rapid change in magnetic field induces a current in the neural tissue. If the current is of sufficient amplitude and duration it will excite nerve tissues.

All patients will undergo a dose titration procedure to establish their convulsive stimulation threshold using 10 second trains at 100Hz. Stimulation will then be provided at 120% of seizure threshold. Patients will undergo a maximum of 15 treatment sessions over approximately 5 weeks.

Stimulation is applied using the Magstim Magnetic Seziure Therapy device. Treatment duration is between 20-30 mins.
Intervention code [1] 257649 0
Treatment: Devices
Comparator / control treatment
Electroconvulsive Therapy (ECT).

ECT uses electrical stimulation to induce a therapeutic seizure.

ECT treatment will be based on seizure threshold which will be determined at the first ECT session. In the majority of subjects we will use right unilateral ECT at three times seizure threshold. Only those patients who have a history of no response to an effective course of unilateral ECT will commence with bilateral ECT at 1.5 times seizure threshold

Patients will undergo a maximum of 15 treatment sessions over approximately 5 weeks.

Stimulation is applied using the Thymatron device. Treatment duration is between 20-30 mins.
Control group
Active

Outcomes
Primary outcome [1] 259698 0
Antidepressant effect.

Montgomery Asberg Depression Rating Scale (MADRS)

Response is defined as a reduction of at least 50% from baseline.
Timepoint [1] 259698 0
MADRS will be assessed at baseline, weekly during treatment, at treatment end, and for responders at 2, 4 and 6 months following treament end.
Secondary outcome [1] 266404 0
Cognitive side effects.

A comprehensive cogntive battery will be administered. The battery will include the Autobiographical Memory Interview, Rey Verbal Auditory Learning Test , Verbal Paired Associates (WMS-R), Logical Memory (WMS-III), and the Brief Visual Spatial Memory Test. We will also include a number of assessments of information processing, i.e. Digit Span, Digit Symbol Coding, and Trail Making Test. Finally, we will look at general intellectual functioning (Wechsler Test of Adult Reading), as well as aspects of executive functioning and language (Rey Complex Figure Test, Stroop, Verbal Fluency and Boston Naming Test).

Post treatment Orientation will also be assessed. Patients will be repeatedly asked to provide their name, date of birth, age, place and day of week. Orientation will be considered to be present when the patient provides correct answers to 4 of these questions.
Timepoint [1] 266404 0
The Cognitive battery will be administered at baseline, endpoint and at 6 months follow up.

Post MST / ECT orientation will be assessed immediately following the first, fourth and ninth treatments.

Eligibility
Key inclusion criteria
Age 18-75 and a DSM-IV diagnosis of a major depressive episode (uni or bipolar depression) (diagnosis made using the standard structured clinical interview for the DSM-IV (SCID I) instrument).

Patients with psychotic symptoms as part of their mood episode will not be excluded if able to give informed consent.

Are referred for or are otherwise suitable for a course of ECT as determined by their treating psychiatrist

Hamilton Depression Rating Scale (17 item version) score of > 18 (moderate – severe depression): note – some authors have defined moderate depression on the 17 item HAMD as >14. We have selected a higher cut off to ensure all patients clearly have depression of substantial clinical severity. It is likely that most patients will have scores in the severe or extremely severe ranges.

Score greater than 23 on the Mini Mental State Examination

Have treatment resistant depression at Stage II of the Thase and Rush classification. This requires failure to respond to adequate courses of several courses of antidepressants.

Demonstrated capacity to give informed consent
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who are too unwell to undergo general anesthetic.

Patients with metallic implants in the head, cardiac pacemakers, cochlear implants or other implanted electronic devices

Treatment with ECT in the last three months

Presence of another DSM-IV Axis I psychiatric disorder (on SCID I) other than bipolar disorder

Presence of substance abuse or dependence during the last six months (on SCID I)

Current pregnancy

Past history of stroke, neurodegenerative disorder or other major neurological illness

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation concealment occurs through central randomisation by computer.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Individuals are randomized (single non stratified sequence) via a computer-generated list
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 258114 0
Government body
Name [1] 258114 0
National Health and Medical Research Council
Address [1] 258114 0
National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601
Country [1] 258114 0
Australia
Primary sponsor type
Individual
Name
Professor Paul Fitzgerald
Address
Monash Alfred Psychiatry Research Centre (MAPrc): Level 4, St Kilda Rd, Melbourne VIC 3004
Country
Australia
Secondary sponsor category [1] 257293 0
Hospital
Name [1] 257293 0
Alfred Hospital
Address [1] 257293 0
55 Commercial Road
PO Box 315 Prahran
Victoria 3181 Australia
Country [1] 257293 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 260098 0
Alfred Hospital Human Research Ethics Committee
Ethics committee address [1] 260098 0
Research & Ethics Unit
Linay Pavilion

55 Commercial Road
PO Box 315 Prahran
Victoria 3181 Australia
Ethics committee country [1] 260098 0
Australia
Date submitted for ethics approval [1] 260098 0
15/11/2010
Approval date [1] 260098 0
21/12/2010
Ethics approval number [1] 260098 0
1/10/0363

Summary
Brief summary
Electro convulsive therapy (ECT) remains the only established treatment for the large percentage of patients with depression who fail to respond to standard therapies. It is commonly used (with 10 to 15% of inpatients with depression receiving ECT) but has substantial problems including the occurrence of cognitive side effects that are often highly distressing for patients. ECT is associated with both short term and long term cognitive side effects. The short term effects include anterograde and retrograde memory loss and post treatment disorientation which can be distressing, dangerous and significantly slow treatment progress. In the longer term, ECT can affect autobiographical memory which can be very distressing to patients. The development of a new treatment with similar efficacy but which minimises these side effects would have great clinical value.

A highly promising possibility is magnetic seizure therapy (MST). MST involves replacing the electrical stimulation used in ECT with a magnetic stimulus. This appears to be able to produce similar clinical effects but without the disabling cognitive side effects related to ECT. However, substantive trials using the newest MST equipment are required. Due to the rarity of the equipment available so far, these studies are only being undertaken in a handful of places internationally and no research with MST has occurred.

Building on a pilot study conducted by the applicants, we propose to undertake a substantive head-to-head trial of MST versus ECT. There will be a total of 60 patients in the study undertaking a treatment course of between 9 and 15 treatments. Baseline and endpoint assessments will be undertaking to investigate efficacy, these will include clinical assessments, cognitive assessments and neurophysiological assessment

If MST proves to be as efficacious as ECT, but with fewer side effects, we anticipate that it could be rapidly adopted in clinical practice. All of the facilities are available for the provision of MST in every substantive mental health service in the country (in current ECT suites / facilities); all that would be required would be the replacement of the ECT machine with MST equipment for seizure induction. Fewer cognitive side effects will enhance patient outcomes and improve treatment acceptability and hence access. In addition, a reduced duration of post treatment disorientation will shorten the period of post treatment observation required enhancing capacity for convulsive therapy to be provided on an outpatient basis, lessening demand on inpatient psychiatric services.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31939 0
Prof Paul Fitzgerald
Address 31939 0
MAPrc Level 4, St Kilda Rd, Melbourne VIC 3004
Country 31939 0
Australia
Phone 31939 0
+ 61 3 9076 6552
Fax 31939 0
Email 31939 0
p.fitzgerald@alfred.org.au
Contact person for public queries
Name 15186 0
Prof Paul Fitzgerald
Address 15186 0
MAPrc Level 4, St Kilda Rd, Melbourne VIC 3004
Country 15186 0
Australia
Phone 15186 0
+ 61 3 9076 6552
Fax 15186 0
Email 15186 0
p.fitzgerald@alfred.org.au
Contact person for scientific queries
Name 6114 0
Prof Paul Fitzgerald
Address 6114 0
MAPrc Level 4, St Kilda Rd, Melbourne VIC 3004
Country 6114 0
Australia
Phone 6114 0
+ 61 3 9076 6552
Fax 6114 0
Email 6114 0
p.fitzgerald@alfred.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment
will require ethical approval
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
Yes
Journal publication details
Publication date and citation/details [1] 478 0
Fitzgerald P, Hoy KE, Elliot D, McQueen S, Wambeek L, Clinton AM, Downey G, Daskalakis ZJ. A Pilot Study of the Comparative Efficacy of 100Hz Magnetic Seizure Therapy and Electroconvulsive Therapy in Persistent Depression. Depression and Anxiety (In Press, Accepted 19/12/2017)
Attachments [1] 478 0
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary