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Trial registered on ANZCTR


Registration number
ACTRN12613000412730
Ethics application status
Approved
Date submitted
26/03/2013
Date registered
15/04/2013
Date last updated
7/06/2021
Date data sharing statement initially provided
20/09/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Deep Brain Stimulation in the Treatment of Depression
Scientific title
Deep Brain Stimulation for the Treatment of Major Depressive Disorder
Secondary ID [1] 282165 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Major Depressive Disorder 288671 0
Condition category
Condition code
Mental Health 289020 289020 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Deep Brain Stimulation is a procedure that involves the surgical implantation of a small panel of closely spaced stimulation electrodes in specific highly localised brain regions. A stimulator (i.e. battery) is also implanted in the chest immediately below the clavicle, and a subcutaneous lead used to connect the electrodes to the stimulator.

Once the device has been implanted and switched on stimulation is delivered consistently to the brain. The stimulation settings are variable and can be adjusted via an external remote control which is operated by the treating physician. The ideal stimulation settings differ between patients, and there is no one "right" set of parameters that are appropriate for everyone.

Throughout the 10-weeks following onset of DBS adjustments to stimulation settings will be made fortnightly. After this period the frequency of adjustments will be made on an individual basis, and will not follow a set schedule. Patients who take part in the study will be observed and and followed up for at least two years following DBS implantation.
Intervention code [1] 286773 0
Treatment: Devices
Comparator / control treatment
Inactive Deep Brain Stimulation: following DBS implantation patients will engage in a 10-week controlled phase of the study where they will be pseudo-randomly allocated to 1 x two-week period of inactive stimulation, 2 x two-week period of low level stimulation (2 volts) and 2 x two week period of moderate level stimulation (4 volts). Following this phase simulation will continue at the most efficacious settings identified for each individual.
Control group
Placebo

Outcomes
Primary outcome [1] 289129 0
Depression severity as assessed by the Montgomery Asberg Depression Rating Scale
Timepoint [1] 289129 0
12-months post stimulation onset
Secondary outcome [1] 301897 0
Cognition as assessed by the following neuropsychologocal battery:

Autobiographical Memory Interview
Benton Visuospatial Memory Test
Rey Auditory Learning Test
Logical Memory I & II (WMS-IV)
Verbal Paired Associates (WMS-IV)
Digit Span (WAIS-IV)
Trail Making Test A & B
Digit Symbol Coding (WAIS-IV)
Controlled Oral Word Association Test
Rey Complex Figure
Tower of London
Golden Stroop
Timepoint [1] 301897 0
Two time points:
6-months post DBS implantation
12 months post DBS implantation

Eligibility
Key inclusion criteria
Patients will be included if they:

1. Have a DSM-IV diagnosis of a major depressive episode as confirmed by interview using the Structured Clinical Interview for DSM IV and review by two independent psychiatrists,

2. Age 18-70 years,

3. Have treatment resistant depression at Stage V of the Thase and Rush classification. This requires failure to respond to adequate courses of at least several different classes of antidepressants and a course of bilateral ECT. We will require patients to have failed to respond to trials of medications from all classes, ECT and cognitive behavioural therapy.

4. Have been depressed for a minimum of three years and have a Montgomery-Asberg Depression Rating Scale score of > 25 (moderate – severe depression),

5. Demonstration of capacity to give informed consent: this will be thoroughly assessed and documented by two independent psychiatrists and a neuropsychologist and via signing of the consent form.
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who:
1. Have an unstable medical condition, neurological disorder or any history of a seizure disorder or are currently pregnant or lactating,

2. Significant concurrent Axis I or II psychiatric morbidity,

3. No evidence of substantive premorbid functioning after the age of 20 and within the last 15 years, including capacity to engage in prolonged relationships and meaningful functional activities (work, study, home-care).

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
We aim to recruit and operate on 16 patients. The sample size is based on assessment of the time taken to assess potential DBS candidates and the work required in post-operative management. If a faster recruitment rate is possible this will be reassessed following 18-months of the study duration. Because of the pilot study nature of this investigation, it is difficult to calculate an accurate power analysis, especially for the initial between stage comparisons. However, the sample of 16 is similar in size to samples that have shown significant differences with stimulation at other sites. In addition, this sample will have power of 0.99 to show a 10 point pre-post improvement in the mean group average on the HAMD (SD 9.0, alpha 0.05).

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Other reasons/comments
Other reasons
With the current sample, the treatment was determined to not be efficacious.
Date of first participant enrolment
Anticipated
15/05/2013
Actual
3/05/2016
Date of last participant enrolment
Anticipated
Actual
9/05/2018
Date of last data collection
Anticipated
31/12/2020
Actual
5/08/2020
Sample size
Target
16
Accrual to date
Final
8
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 286930 0
University
Name [1] 286930 0
Monash Alfred Psychiatry Research Centre
Country [1] 286930 0
Australia
Funding source category [2] 292215 0
Government body
Name [2] 292215 0
National Health and Medical Research Council
Country [2] 292215 0
Australia
Primary sponsor type
University
Name
Monash Alfred Psychiatry Research Centre
Address
607 St Kilda Rd
Prahran, VIC
3004
Country
Australia
Secondary sponsor category [1] 285718 0
None
Name [1] 285718 0
Address [1] 285718 0
Country [1] 285718 0
Other collaborator category [1] 277325 0
Individual
Name [1] 277325 0
Prof Richard Bittar
Address [1] 277325 0
Royal Melbourne Hospital
Grattan St
Parkville VIC
3050
Country [1] 277325 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288986 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 288986 0
Level 5, 553 St Kilda Rd, Melbourne, VIC, 3004
Ethics committee country [1] 288986 0
Australia
Date submitted for ethics approval [1] 288986 0
03/04/2013
Approval date [1] 288986 0
03/07/2015
Ethics approval number [1] 288986 0
272/15

Summary
Brief summary
Major depressive disorder is a common psychiatric illness that in a small subset of patients fails to respond to multiple trials of standard treatments including medication, psychotherapy and electroconvulsive therapy. In recent years, deep brain stimulation (DBS) has begun to be investigated as a novel intervention for patients with this kind of severe treatment resistant depression. In the proposed study, we will investigate the therapeutic efficacy of DBS applied to the bed nucleus of the stria terminalis. This brain region is an important junction point in depression relevant brain circuitry. We have obtained highly promising results in our pilot study of DBS applied to this brain region. In the proposed study, 16 patients will undergo the DBS operative procedure. Stimulation will be commenced in a randomised, controlled manner, including periods of active and sham stimulation and antidepressant responses will be evaluated in a blinded manner.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 38678 0
Prof Paul Fitzgerald
Address 38678 0
Epworth Centre for Innovation in Mental Health (ECIMH), Epworth HealthCare, 888 Toorak Rd, Camberwell, Vic 3124
Country 38678 0
Australia
Phone 38678 0
+61 3 9805 4287
Fax 38678 0
Email 38678 0
[email protected]
Contact person for public queries
Name 38679 0
Sally Herring
Address 38679 0
Epworth Centre for Innovation in Mental Health (ECIMH), Epworth HealthCare, 888 Toorak Rd, Camberwell, Vic 3124
Country 38679 0
Australia
Phone 38679 0
+61 3 9805 4126
Fax 38679 0
Email 38679 0
[email protected]
Contact person for scientific queries
Name 38680 0
Paul Fitzgerald
Address 38680 0
Epworth Centre for Innovation in Mental Health (ECIMH), Epworth HealthCare, 888 Toorak Rd, Camberwell, Vic 3124
Country 38680 0
Australia
Phone 38680 0
+61 3 9805 4287
Fax 38680 0
Email 38680 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Consent not provided by participants to do this.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Embase"Nothing to Lose, Absolutely Everything to Gain": Patient and Caregiver Expectations and Subjective Outcomes of Deep Brain Stimulation for Treatment-Resistant Depression.2021https://dx.doi.org/10.3389/fnhum.2021.755276
N.B. These documents automatically identified may not have been verified by the study sponsor.