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Trial registered on ANZCTR


Registration number
ACTRN12612001142820
Ethics application status
Approved
Date submitted
24/10/2012
Date registered
29/10/2012
Date last updated
4/04/2019
Date data sharing statement initially provided
4/04/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Deep Brain Stimulation (DBS) in Treatment Refractory Obsessive-Compulsive Disorder (OCD)
Scientific title
A study on the effectiveness of Deep Brain Stimulation (DBS) in Treatment Refractory Obsessive-Compulsive Disorder (OCD)
Secondary ID [1] 281434 0
Nil
Universal Trial Number (UTN)
Trial acronym
DBS in OCD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Treatment Refractory Obsessive-Compulsive Disorder 287693 0
Condition category
Condition code
Mental Health 288030 288030 0 0
Anxiety

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The aims of this study are to determine the efficacy of Deep Brain Stimulation in treatment refractory OCD. This is in tandem with functional neuroimaging and neuropsychological assessment to evaluate the impact of DBS implantation on neuropsychological, magnetoencephalographic functioning, and intracerebral blood flow and metabolism.
There are no wash-out or break periods in between each phase of the treatment when participants do not undergo any of the treatments.

The study will consist of 3 sequential treatment phases.
i)After electrode implantation, participants will enter an open phase of 8 months during which they will be evaluated every 2 weeks for severity of symptoms and optimal stimulation parameters.
Once an initial and substantial decrease (6 points) in Y-BOCS score has been obtained, a standardized CBT program will be added.

Treatment with CBT will consist of weekly individual sessions of 60 minutes for 24 weeks.

ii)After the open phase, participants will enter a 1-month, double blind, sham-controlled phase. Participants will be randomly allocated to 2 periods of 2 weeks with the stimulators blindly turned on (active stimulation) in one period and turned off (sham stimulation) in the other period. Block randomization will be used with computer-generated random sequence, providing adequate concealment.

Participants will be assessed 3 times (refer to outcome measures below), at baseline, after a 2-week period of active or sham stimulation, and after the second 2-week period of reversed active or sham stimulation). The assessor will be blinded to stimulation conditions.

Treatment with CBT will consist of weekly individual sessions of 60 minutes for 24 weeks. The CBT sessions will focus on exposure and response prevention, as well as addressing avoidance. The CBT sessions will be undertaken by a psychiatrist skilled in CBT, which may be either one of the study psychiatrists or a treating psychiatrist. The CBT will not be manualized and will be treatment as usual CBT for severe OCD.

In terms of psychotropic medication, participants will continue with their prescribed medication for OCD without change for 2 months prior to implantation and with continuation during the first 2 phases of the study (that is for 9 months after implantation).

iii)The ensuing maintenance phase will last for 12 months, during which participants will be evaluated, utilising outcome measures below, at 3-month intervals. The stimulators will be turned on for all participants, and stimulation parameters will be adjusted if necessary.

Surgical Procedure
Implantation of the electrodes will be performed according to standard stereotactic procedures using frame-based magnetic resonance imaging for target determination. All patients will undergo bilateral implantation of 4 direct-contact electrodes (model 3389; Medtronic Inc, Minneapolis, Minnesota), with contact points 1.5-mm long and separated from adjacent contacts by 0.5 mm. The MEDTRONIC Deep brain stimulation lead Model 3389 has four platinum iridium electrodes, which are spaced 0.5 mm apart. The contacts are coded from 0 (ventral) to 3 (dorsal) and are independently programmable.

Target coordinates for the electrode tip are 7 mm lateral to the midline, 3 mm anterior to the anterior border of the anterior commissure, and 4 mm inferior to the intercommissural line. Electrodes will be implanted following the anterior limb of the internal capsule into the target nucleus, with an anterior angle of approximately 75° to the intercommissural line. Electrodes will be connected via subcutaneous extensions to stimulators (Activa, Medtronic Inc) placed bilaterally in an infraclavicular pocket under general anaesthesia. Postoperative frame-based computed tomography images or radiographs will be used to verify the position of the implanted electrodes. Electrode and therapeutic impedances of the DBS device will be measured intraoperatively.

Stimulation parameters
Stimulation parameters will follow standard parameters, which will not be exceeded, hence: to a frequency of 120-180 Hz; and a pulse width of 60 to 90 microseconds. Optimization will be limited to changes in active contact points and voltage, ranging to a maximum of 6.0 V. Stimulation will be cyclic during the 8 month open phase and twelve month maintenance phases, as tolerated in terms of obsessive-compulsive symptomatology- 30 seconds on, 2 minutes off, 30 seconds on, 2 minutes off- to maximise battery life. If cyclic stimulation is poorly tolerated in terms of obsessive-compulsive symptomatology, then continuous stimulation during the open and maintenance phases will be utilised. The cyclic or continuous active stimulation utilised at the end of the 8 month open phase will continue during the 1-month, double blind, sham-controlled phase.
Intervention code [1] 285940 0
Treatment: Devices
Comparator / control treatment
The study will consist of 3 sequential treatment phases.
i)After electrode implantation, participants will enter an open phase of 8 months during which they will be evaluated every 2 weeks for severity of symptoms and optimal stimulation parameters.

Once an initial and substantial decrease (6 points) in Y-BOCS score has been obtained, a standardized CBT program will be added. Treatment with CBT will consist of weekly individual sessions of 60 minutes for 24 weeks.

ii)After the open phase, participants will enter a 1-month, double blind, sham-controlled phase. Participants will be randomly allocated to 2 periods of 2 weeks with the stimulators blindly turned on (active stimulation) in one period and turned off (sham stimulation) in the other period. Participants will be assessed 3 times (refer to outcome measures below), at baseline, after a 2-week period of active or sham stimulation, and after the second 2-week period of reversed active or sham stimulation).
Control group
Placebo

Outcomes
Primary outcome [1] 288238 0
Obsessive-compulsive symptoms will be measured using the YBOCS, and participants will be defined as responders if they have a score decrease of at least 35% on the Y-BOCS.
Timepoint [1] 288238 0
The study will consist of 3 sequential treatment phases.
i)After electrode implantation, participants will enter an open phase of 8 months during which they will be evaluated every 2 weeks for severity of symptoms and optimal stimulation parameters.

Once an initial and substantial decrease (6 points) in Y-BOCS score has been obtained, a standardized CBT program will be added. Treatment with CBT will consist of weekly individual sessions of 60 minutes for 24 weeks.

ii)After the open phase, participants will enter a 1-month, double blind, sham-controlled phase. Participants will be randomly allocated to 2 periods of 2 weeks with the stimulators blindly turned on (active stimulation) in one period and turned off (sham stimulation) in the other period. Participants will be assessed 3 times (refer to outcome measures below), at baseline, after a 2-week period of active or sham stimulation, and after the second 2-week period of reversed active or sham stimulation).

iii)The ensuing maintenance phase will last for 12 months, during which participants will be evaluated, utilising outcome measures below, at 3-month intervals. The stimulators will be turned on for all participants, and stimulation parameters will be adjusted if necessary.
Primary outcome [2] 288247 0
Depression will be rated using the 17-item Hamilton Scale for Depression (HAM-D),14 and anxiety will be evaluated using the Hamilton Anxiety Scale (HAM-A).
Timepoint [2] 288247 0
The study will consist of 3 sequential treatment phases.
i)After electrode implantation, participants will enter an open phase of 8 months during which they will be evaluated every 2 weeks for severity of symptoms and optimal stimulation parameters.

Once an initial and substantial decrease (6 points) in Y-BOCS score has been obtained, a standardized CBT program will be added. Treatment with CBT will consist of weekly individual sessions of 60 minutes for 24 weeks.

ii)After the open phase, participants will enter a 1-month, double blind, sham-controlled phase. Participants will be randomly allocated to 2 periods of 2 weeks with the stimulators blindly turned on (active stimulation) in one period and turned off (sham stimulation) in the other period. Participants will be assessed 3 times (refer to outcome measures below), at baseline, after a 2-week period of active or sham stimulation, and after the second 2-week period of reversed active or sham stimulation).

iii)The ensuing maintenance phase will last for 12 months, during which participants will be evaluated, utilising outcome measures below, at 3-month intervals. The stimulators will be turned on for all participants, and stimulation parameters will be adjusted if necessary.
Primary outcome [3] 288248 0
The Brown Assessment of Beliefs Scale (BABS) will be used to assess delusional characteristics of obsessions.
Timepoint [3] 288248 0
The study will consist of 3 sequential treatment phases.
i)After electrode implantation, participants will enter an open phase of 8 months during which they will be evaluated every 2 weeks for severity of symptoms and optimal stimulation parameters.

Once an initial and substantial decrease (6 points) in Y-BOCS score has been obtained, a standardized CBT program will be added. Treatment with CBT will consist of weekly individual sessions of 60 minutes for 24 weeks.

ii)After the open phase, participants will enter a 1-month, double blind, sham-controlled phase. Participants will be randomly allocated to 2 periods of 2 weeks with the stimulators blindly turned on (active stimulation) in one period and turned off (sham stimulation) in the other period. Participants will be assessed 3 times (refer to outcome measures below), at baseline, after a 2-week period of active or sham stimulation, and after the second 2-week period of reversed active or sham stimulation).

iii)The ensuing maintenance phase will last for 12 months, during which participants will be evaluated, utilising outcome measures below, at 3-month intervals. The stimulators will be turned on for all participants, and stimulation parameters will be adjusted if necessary.
Secondary outcome [1] 299678 0
Cognitive Battery
1)Wechsler Test of Adult of Reading
2)Autobiographical Memory Interview
3)Benton Visuospatial Memory Test
4)California Verbal Learning Test
5)Logical Memory I & II(WMS-IV & Aust Alt Forms)
6)Verbal Paired Associates (WMS-IV)
7)Digit Span (WAIS-IV)
8)Trails
9)Digit Symbol Coding (WAIS-IV)
10)Controlled Oral Word Association Test
11)5 Point Test
12)Boston Naming Test
13)Rey Complex Figure
14)Tower of London
15)Hayling
16)Brixton
Timepoint [1] 299678 0
Participants will have neuropsychological, MEG and PET scans of the brain (performed within 2 months of DBS implantation [baseline] and at 8 months post DBS implantation).
Secondary outcome [2] 299690 0
Affective Tasks:
1)MSCEIT
2)Balloon Analogue Risk Task
Timepoint [2] 299690 0
Participants will have neuropsychological, MEG and PET scans of the brain (performed within 2 months of DBS implantation [baseline] and at 8 months post DBS implantation).
Secondary outcome [3] 299691 0
Magnetoencephalogram (MEG) assessment
1)Monetary Incentive Delay Task
2)Spatial working memory taska
Timepoint [3] 299691 0
Participants will have neuropsychological, MEG and PET scans of the brain (performed within 2 months of DBS implantation [baseline] and at 8 months post DBS implantation).
Secondary outcome [4] 299702 0
The Sheehan Disability Scale will be used to assess overall symptomatic and functional impairment.
Timepoint [4] 299702 0
The study will consist of 3 sequential treatment phases.
i)After electrode implantation, participants will enter an open phase of 8 months during which they will be evaluated every 2 weeks for severity of symptoms and optimal stimulation parameters.

Once an initial and substantial decrease (6 points) in Y-BOCS score has been obtained, a standardized CBT program will be added. Treatment with CBT will consist of weekly individual sessions of 60 minutes for 24 weeks.

ii)After the open phase, participants will enter a 1-month, double blind, sham-controlled phase. Participants will be randomly allocated to 2 periods of 2 weeks with the stimulators blindly turned on (active stimulation) in one period and turned off (sham stimulation) in the other period. Participants will be assessed 3 times (refer to outcome measures below), at baseline, after a 2-week period of active or sham stimulation, and after the second 2-week period of reversed active or sham stimulation).

iii)The ensuing maintenance phase will last for 12 months, during which participants will be evaluated, utilising outcome measures below, at 3-month intervals. The stimulators will be turned on for all participants, and stimulation parameters will be adjusted if necessary.

Eligibility
Key inclusion criteria
i) Male or female outpatients, aged 18 to 65 years, with a primary DSM-IV diagnosis OCD.
ii) Yale-Brown Obsessive Compulsive Scale (Y-BOCS) greater than or equal to 24, measured twice at least 2 weeks apart.
iii) At least a 5-year history of OCD and substantial functional impairment according to DSM-IV criterion C and a Global Assessment of Function score of <45.
iv) Refractoriness to therapy: defined as no response or insufficient response following at least 2 treatments with a selective serotonin reuptake inhibitor at maximum dosage for at least 12 weeks, plus 1 treatment with clomipramine hydrochloride at maximum dosage for at least 12 weeks, plus at least 1 augmentation trial with an atypical antipsychotic for 8 weeks in combination with an selective serotonin reuptake inhibitor, plus at least 1 Cognitive-Behavioural Therapy (CBT) trial for a minimum of 16 sessions.
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
i) Except for those with major depressive disorder and mild anxiety disorders, people with clinically significant comorbid DSM-IV diagnoses (such as schizophrenia, bipolar II disorder, alcohol or substance abuse in the last 6 months, current tic disorder, or body dysmorphic disorder) will be excluded from the study. The confirmation of the diagnosis of OCD and the exclusion of these diagnoses will require utilisation of the Structured Clinical Interview for DSM IV.
ii) People with severe personality disorders, and clinically significant and unstable neurological or medical illnesses will be excluded.

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)
There will be up to 12 participants recruited into this study. Participants will be identified by treating psychiatrists and will be deemed eligible to be involved based on the inclusion criteria listed. In addition, all participants must have an application made by A/Prof Peter Bosanac for neurosurgery for mental illness to the Mental Health Tribunal, Victoria, and subsequent approval prior to the DBS surgical procedure occurring. Participants will need to consent to their relevant medical records and previous psychological tests, blood tests and brain images to be provided to the Mental Health Tribunal. Participants will be assessed by an independent psychiatrist in regard to neurosurgery for mental illness, prior to the application to the Mental Health Tribunal..
Following surgery, the neurosurgeon must submit a report within 3 months covering the surgical procedure, post-operative progress and the handover back to psychiatric care. In addition, the treating psychiatrist must submit reports at approximately 3 and 12 months detailing the psychiatric and medical follow up during the post-operative period.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
3 sequential phases as previously described .
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
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] 286201 0
Hospital
Name [1] 286201 0
St Vincent's
Address [1] 286201 0
41 Victoria Parade, Fitzroy VIC 3065
Country [1] 286201 0
Australia
Primary sponsor type
Hospital
Name
St Vincent's
Address
41 Victoria Parade, Fitzroy VIC 3065
Country
Australia
Secondary sponsor category [1] 285010 0
None
Name [1] 285010 0
Address [1] 285010 0
Country [1] 285010 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288285 0
HREC-D St Vincent's
Ethics committee address [1] 288285 0
41 Victoria Pde Fitzroy 3065
Ethics committee country [1] 288285 0
Australia
Date submitted for ethics approval [1] 288285 0
26/11/2012
Approval date [1] 288285 0
03/04/2013
Ethics approval number [1] 288285 0

Summary
Brief summary
The aim of this study is to assess the extent to which Deep Brain Stimulation (DBS) may help people suffering with treatment refractory Obsessive-Compulsive Disorder (OCD) and to evaluate how psychological functioning and activity within the brain is affected by DBS.
There will be up to 12 participants with treatment refractory (not responding to multiple other treatments) obsessive-compulsive disorder (OCD) recruited into this study.
Participants will be participating in a cross-over study, in which each participant has different phases of treatments (see below), in turn.
The study will consist of 3 sequential treatment phases.
i) After DBS implantation by surgery, participants will enter an open phase of 8 months during which they will be evaluated every 2 weeks (each visit will take approximately 60 minutes) for severity of symptoms and optimal adjustment of the settings of the DBS device. Once an initial and substantial decrease (6 points) in Y-BOCS score (a measure of OCD severity) has been obtained, a CBT (cognitive-behavioural therapy; a psychological treatment) program will be added.
ii )After the above open phase (in which the participant knows that the DBS device is switched on), participants will enter an optional 1-month, blinded, sham-controlled phase, in which they do not know whether the DBS device is switched on or off. Participants will be randomly allocated to this phase of the study, with 2 periods of 2 weeks with the stimulators blindly turned on (active stimulation) in one period and turned off (sham stimulation) in the other period. A computer-generated random sequence, will be used to allocate active or sham treatment. Participants will be assessed 3 times (at baseline, after a 2-week period of active or sham stimulation, and after the second 2-week period of reversed active or sham stimulation), with each visit being approximately 60 minutes in duration. Treatment with CBT will be continued during this phase.
iii)The ensuing maintenance phase will continue, during which participants will be evaluated at 3-month intervals. Each visit will last approximately 60 minutes. The stimulators will be turned on for all participants, and stimulation parameters will be adjusted if necessary.
In terms of psychotropic medication, participants will continue with their prescribed medication for OCD without change for 2 months prior to implantation and with continuation during the first 2 phases of the study (that is for 9 months after implantation).
Participants will have neuropsychological, MEG and PET scans of the brain, as described , if they consent to do so. If participants do not consent to any component of these, they will still be required to continue in the open, double-blind sham-controlled and maintenance phases of study to continue in the study, as well any of the neuropsychological, MEG and PET components of the study that they consent to, without coercion or prejudice to their care.
The batteries in the DBS device will have to be changed possibly within 12 to 24 months, if a non-rechargeable neurostimulator (does not require regular recharging of the battery by participants) is used, and up to 9 years if a rechargeable neurostimulator (requires regular recharging of the battery by participants, approximately one to three times weekly) and also depending on settings,usage. The selection of a rechargeable or non-rechargeable neurostimulator is based on participant preference about monitoring and recharging the battery in the neurostimulator. Replacement of the neurostimulator requires additional surgery, under a general anaesthetic, to remove and change it in its position under the collar bone.
Trial website
None.
Trial related presentations / publications
None at present.
Public notes

Contacts
Principal investigator
Name 34869 0
A/Prof A/Prof Peter Bosanac
Address 34869 0
St Vincent's Mental Health, PO Box 2900, Fitzroy 3065, Victoria.
Country 34869 0
Australia
Phone 34869 0
+61392884329
Fax 34869 0
Email 34869 0
peter.bosanac@svha.org.au
Contact person for public queries
Name 18116 0
A/Prof A/Prof Peter Bosanac
Address 18116 0
St Vincent's Mental Health, 46 Nicholson St, Fitzroy 3065, Melbourne, Victoria.
Country 18116 0
Australia
Phone 18116 0
+61 392314329
Fax 18116 0
Email 18116 0
peter.bosanac@svha.org.au
Contact person for scientific queries
Name 9044 0
A/Prof A/Prof Peter Bosanac
Address 9044 0
St Vincent's Mental Health, 46 Nicholson St, Fitzroy 3065, Melbourne, Victoria.
Country 9044 0
Australia
Phone 9044 0
+61 392314329
Fax 9044 0
Email 9044 0
peter.bosanac@svha.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual data will be analysed as a group.
What supporting documents are/will be available?
No other documents available
Summary results
No Results