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Trial registered on ANZCTR


Registration number
ACTRN12615000416594
Ethics application status
Approved
Date submitted
16/04/2015
Date registered
1/05/2015
Date last updated
1/05/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
Neurobiological correlates of improvements in depression with repetitive transcranial magnetic stimulation
Scientific title
Sleep-wake cycle, neuropsychological and neurochemical correlates of improvements in depression in young people with repetitive transcranial magnetic stimulation treatment
Secondary ID [1] 286542 0
NIL
Universal Trial Number (UTN)
U1111-1169-3503
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Depression 294779 0
Condition category
Condition code
Mental Health 295062 295062 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive procedure which has been approved by the TGA to treat depression in adults who have failed to respond to at least 2 adequate trials of an antidepressant medication. Our rTMS protocol involves 20 sessions of 20 minutes over 4 weeks. rTMS sessions will be administered for 5 days in a row with a 2 days break in between (i.e. rTMS from Monday through to Friday and no rTMS on Saturday and Sunday) and can commence on either weekday or weekend depending on nursing staff timetabling. rTMS will be administered using a MagPro R30 (MagVenture). A single pulse to the motor cortex will measure motor threshold (MT) before commencement of treatment. High-frequency (20 Hz) stimulation at 120% of MT will be applied to the left dorsolateral prefrontal cortex left for 45 trains of 4 seconds with 26 seconds between trains (i.e. 1800 pulses per day). Site of stimulation will be determined using the Acsension MINIBIRD tracker in combination with MRIcro/MRIreg software packages and a 3D structural T1-weighted MRI scan, according to a standard technique.
Intervention code [1] 291646 0
Treatment: Devices
Comparator / control treatment
NIL
Control group
Uncontrolled

Outcomes
Primary outcome [1] 294828 0
Sleep-wake cycle is the primary outcome and will be measured by actigraphy, an effective method for objectively determining sleep-wake pattern. This involves wearing an actigraph, that is, a ‘wrist watch’ which measures and records the movements of a person. The participant will be required to wear the actigraph during day and night (except when the participant will be in contact with water or a magnetic field) in order for their sleep-wake cycle (i.e. activity-rest pattern) can be assessed. After at least 10 days, a study investigator will collect the actigraph and download the data onto a designated computer. Actigraphy data will be stored on select designated computers in password protected electronic files which will only be accessible to study investigators.
Timepoint [1] 294828 0
pre-treatment and post-treatment time points (i.e. within 2 weeks prior and 2 weeks after treatment).
Primary outcome [2] 294912 0
The Quick Inventory of Depressive Symptomatology clinician rating (QIDS-C) will measure change in depressive symptoms with rTMS treatment.
Timepoint [2] 294912 0
pre- and post-treatment time points (i.e. within 2 weeks prior and 2 weeks after treatment).
Secondary outcome [1] 314172 0
Cognitive functions will be assessed as a secondary outcome. A standardised battery of neuropsychological tests (traditional and computer based) currently used in a larger research program at our institute will be administered. The traditional neuropsychological tests to be used are: Wechsler Test of Adult Reading, Controlled Oral Word Association Test, Logical Memory (WMS-III), Rey Auditory Verbal Learning Test, Trail Making Test and Rey Complex Figure Test. Computer based tests are Reading the Mind in the Eyes Test and Movie Stills (both to assess social cognition) and a Cambridge Neuropsychological Test Automated Battery (CANTAB) with the tests Motor Screening, Spatial Span, Reaction Time, Rapid Visual Information Processing, Intra/Extradimensional Shift, Paired Associates Learning and Affective Go/NoGo.
Timepoint [1] 314172 0
pre- and post-treatment time points (i.e. within 2 weeks prior and 2 weeks after treatment).
Secondary outcome [2] 314173 0
In vivo gamma-aminobutyric acid (GABA) concentrations in the posterior brain will be measured as a secondary outcome using proton magnetic resonance spectroscopy conducted on a 3Tesla GE Discovery MR750 Magnetic Resonance Imaging scanner and in vivo GABA will be resolved using MEGAPRESS.
Timepoint [2] 314173 0
pre- and post-treatment time points (i.e. within 2 weeks prior and 2 weeks after treatment).
Secondary outcome [3] 314326 0
The Quick Inventory of Depressive Symptomatology clinician rating (QIDS-C) will measure change in depressive symptoms with rTMS treatment.
Timepoint [3] 314326 0
pre- and post-treatment time points (i.e. within 2 weeks prior and 2 weeks after treatment).

Eligibility
Key inclusion criteria
aged 18-30 years old with stable moderate to severe depressive symptoms and who have not responded to at least two adequate trials of antidepressant medications.
Minimum age
18 Years
Maximum age
30 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Current diagnosis of epilepsy; mania, psychosis, high suicidal risk, and severe restrictive eating disorders; major developmental disorders; current alcohol and other substance use disorders; major medical illness; intellectual disability or inability to provide informed consent; poor English speaking; history of sustained head injury (loss of consciousness > 30 minutes); pregnancy; contraindication to MRI scanning.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
There will only be one group in the study. All participants would have been prescribed rTMS by their treating psychiatrist. We will measure sleep-wake cycle, cognitive functioning and in vivo brain chemical concentrations before and after the treatment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Data will be analysed using multiple regression analyses to examine whether changes in neurobiological measures will be predictive of improvements in depression. Having accounted for a 20% attrition rate, a priori power analysis showed that a sample of 125 would be sufficient for a regression with three predictor variables to detect a relationship between the predictors (phase delay, in vivo GABA concentration and a cognitive measure) and the dependent variable (reduction in depressive symptoms) with a small to medium effect size (f2 =0.09) with 89% power at an alpha of 0.05.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/05/2015
Actual
Date of last participant enrolment
Anticipated
1/08/2018
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
160
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 3712 0
St Vincent's Private Hospital (Darlinghurst) - Darlinghurst
Recruitment postcode(s) [1] 9537 0
2010 - Darlinghurst

Funding & Sponsors
Funding source category [1] 291109 0
Charities/Societies/Foundations
Name [1] 291109 0
The Ritchie Foundation
Country [1] 291109 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
The University of Sydney, NSW 2006
Country
Australia
Secondary sponsor category [1] 289785 0
None
Name [1] 289785 0
Address [1] 289785 0
Country [1] 289785 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292687 0
St Vincent's Hospital
Ethics committee address [1] 292687 0
Level 6, de Lacy Building
St Vincent’s Hospital
390 Victoria Street
Darlinghurst NSW 2010
Ethics committee country [1] 292687 0
Australia
Date submitted for ethics approval [1] 292687 0
Approval date [1] 292687 0
26/11/2014
Ethics approval number [1] 292687 0
Ethics committee name [2] 292688 0
University of Sydney
Ethics committee address [2] 292688 0
Human Ethics Office
Margaret Telfer Building (K07)
University of Sydney
NSW 2006
Ethics committee country [2] 292688 0
Australia
Date submitted for ethics approval [2] 292688 0
Approval date [2] 292688 0
03/03/2015
Ethics approval number [2] 292688 0

Summary
Brief summary
Repetitive transcranial magnetic stimulation has been shown to be efficacious for treating depression and has been approved by the TGA for the treatment of depression in adults who have not responded to at least 2 trials of antidepressant medications. However, some people do not respond to the treatment. Sleep-wake cycle disruption, reduced cognitive functioning and changes in brain chemistry are prominent features of depression. It is unclear how rTMS affects these features and whether they are associated with response to rTMS treatment. We seek to investigate whether these features of patients are associated with rTMS treatment response.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 56582 0
Prof Ian Hickie
Address 56582 0
The Brain and Mind Research Institute, 94 Mallett Street, Camperdown, NSW 2050
Country 56582 0
Australia
Phone 56582 0
+61293510810
Fax 56582 0
Email 56582 0
[email protected]
Contact person for public queries
Name 56583 0
Manreena Kaur
Address 56583 0
The Brain and Mind Research Institute, 94 Mallett Street, Camperdown, NSW 2050
Country 56583 0
Australia
Phone 56583 0
+61293510932
Fax 56583 0
Email 56583 0
[email protected]
Contact person for scientific queries
Name 56584 0
Manreena Kaur
Address 56584 0
The Brain and Mind Research Institute, 94 Mallett Street, Camperdown, NSW 2050
Country 56584 0
Australia
Phone 56584 0
+61293510932
Fax 56584 0
Email 56584 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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