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Trial registered on ANZCTR


Registration number
ACTRN12610001071011
Ethics application status
Approved
Date submitted
22/11/2010
Date registered
6/12/2010
Date last updated
29/06/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating predictors of response to Transcranial Magnetic Stimulation for the treatment of depression
Scientific title
Investigating predictors of the antidepressant efficacy of Transcranial Magnetic Stimulation
Secondary ID [1] 253135 0
Project 303/10
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Treatment resistant depression 258694 0
Condition category
Condition code
Mental Health 258838 258838 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Transcranial Magentic Stimulation (TMS).

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.

Patients will receive left sided high frequncy TMS intially, if they do not respond after three weeks they will be randomised to either; continue left sided high frequnecy treatment, crossover over to right sided low frequency TMS or sequential bilateral TMS (i.e. right sided low frequency followed by left sided high frequency).

Daily treatment (Mon-Fri) at 110% of motor threshold, for between 5 and 8 weeks.
Intervention code [1] 257650 0
Treatment: Devices
Comparator / control treatment
There will be a group of healthy controls who will undergo the predictor measures at baseline for comparison.
Control group
Active

Outcomes
Primary outcome [1] 259699 0
Antidepressant effects.

Montgomery Asberg Depression Rating Scale (MADRS)

A reduction of at least 50% on this rating scale indicates response.
Timepoint [1] 259699 0
The MADRS will be administered at baseline, weeks 1, 4, 7 and 10.
Secondary outcome [1] 266405 0
Predictors of Response to TMS.

Specifically, we will test the potential predictive capacity of several electrophysiological techniques:

1. Resting and task related frontal alpha electroencephalography (EEG) activity: Extensive research has demonstrated a relationship between resting frontal alpha activity in depression. More recent research has indicated a substantive functional role of alpha in tasks such as cognitive inhibition. This active alpha activity may provide a more functionally useful measure of alpha as it could potentially relate to response to treatment.

2. TMS-EEG measures of cortical inhibition: We have recently pioneered a technique combining single and paired pulse TMS stimulation with EEG to measure the activity of inhibitory GABAergic activity in cortical regions such as the dorsolateral prefrontal cortex (DLPFC). GABA activity has previously been shown to be reduced in patients with depression and to increase with successful treatment although no methods have been available to evaluate functional GABA activity and its relationship to treatment response before now.
3. Near infrared spectroscopy (NIRS) is a technique for non invasively measuring cortical blood flow by assaying changes in absorption and diffraction of near infrared light produced by changes in oxygenated and deoxygenated haemoglobin. We have successfully recorded blood flow changes with NIRS during prefrontal TMS and will explore whether the immediate reduction in oxygenated haemoglobin seen in local cortical regions during TMS treatment is associated with treatment response.
Timepoint [1] 266405 0
The predictors will be measured at baseline weeks, 1, 4 and 7 weeks.

Eligibility
Key inclusion criteria
Have a DSM-IV diagnosis of a Major Depressive Episode (SCID II).

Are aged 18-75.

Have treatment resistant depression at Stage III of the Thase and Rush classification (27).

Have a Hamilton Depression Rating Scale (HAMD) score of > 20 (moderate to severe depression).

Have had no increase or initiation of new antidepressant (or other psychoactive) therapy in the 4 weeks prior to screening
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Have an unstable medical condition, neurological disorder, any history of a seizure disorder, or are currently pregnant or lactating.

In the opinion of the investigator, are at sufficient risk of suicide to require immediate electroconvulsive therapy.

Have a current DSM-IV diagnosis of Substance Abuse or Dependence disorder, a diagnosis of a personality disorder (SCID II) or another Axis 1 disorder.

Control participants will have no history of neurological or psychiatric illness and be taking no medications.

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)
Patients will receive left sided high frequncy TMS intially, if they do not respond after three weeks they will be randomised to either; continue left sided high frequnecy treatment, crossover over to right sided low frequency TMS or sequential bilateral TMS (i.e. right sided low frequency followed by left sided high frequency). Allocation was concealed via central randomisation by phone/fax/computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomization will occur via the generation of a single computer number sequence.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint(s)
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] 258115 0
Self funded/Unfunded
Name [1] 258115 0
Address [1] 258115 0
Country [1] 258115 0
Primary sponsor type
Individual
Name
Professor Paul Fitzgerald
Address
Monash Alfred Psychiatry Research Centre
Level One Old Baker Bld
Alfred Hospital
Commerical Rd
Prahran
VIC 3181
Country
Australia
Secondary sponsor category [1] 257294 0
Hospital
Name [1] 257294 0
Alfred Hospital
Address [1] 257294 0
55 Commercial Road
PO Box 315 Prahran
Victoria 3181 Australia
Country [1] 257294 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 260099 0
Alfred Hospital Human Research Ethics Committee
Ethics committee address [1] 260099 0
Research & Ethics Unit
Linay Pavilion
The Alfred
55 Commercial Road
PO Box 315 Prahran
Victoria 3181 Australia
Ethics committee country [1] 260099 0
Australia
Date submitted for ethics approval [1] 260099 0
Approval date [1] 260099 0
22/10/2010
Ethics approval number [1] 260099 0
1/10/0303

Summary
Brief summary
Major depressive disorder (MDD) is common, associated with considerable disability and high morbidity and often resistant to treatment with standard approaches (~30% of patients meet standard definitions for treatment resistant depression (TRD)). There is currently an overwhelming need in the community for the development of better and novel treatments for depression. Despite the demand, there are relatively few treatment options available to patients with TRD. One of the only substantially new treatments developed in recent years has been repetitive transcranial magnetic stimulation (rTMS). Despite the considerable bulk of evidence demonstrating that rTMS can be effective in the treatment of depression, a major issue that limits its wider use is that only between 40-50% of patients respond to rTMS treatment. While this is a good response rate in a group of patients with significant depression who have failed to respond to other treatments, participation in rTMS treatment involves a considerable commitment of time and resources (stimulation is usually provided five days per week to outpatients who attend for up to six weeks). It is therefore essential to be able to identify patients who are more or less likely to respond to treatment. This research aims to provide a practical and clinically useful approach to predicting antidepressant response to rTMS treatment. In addition, by providing greater information about the underlying causes of depression and how these interact with treatments, this research may ultimately assist in developing more effective therapies for TRD. This would have a significant impact on the considerable numbers of Australians with depression who have tried standard therapies and yet remain significantly unwell. Therefore the current project aims to use both novel and more established neuroscience methodologies (namely electroencephalogy (EEG), TMS and near infra-red spectroscopy (NIRS)) to investigate whether such techniques can be used to predict response to rTMS treatment in depression.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31940 0
Prof Paul Fitzgerald
Address 31940 0
MAPrc
Level 4, 607 St Kilda Road,
Melbourne, Victoria
3004
Country 31940 0
Australia
Phone 31940 0
+61 3 9076 6552
Fax 31940 0
Email 31940 0
paul.fitzgerald@monash.edu
Contact person for public queries
Name 15187 0
Prof Paul Fitzgerald
Address 15187 0
MAPrc
Level 4, 607 St Kilda Road,
Melbourne, Victoria
3004
Country 15187 0
Australia
Phone 15187 0
+61 3 9076 6552
Fax 15187 0
Email 15187 0
paul.fitzgerald@monash.edu
Contact person for scientific queries
Name 6115 0
Prof Paul Fitzgerald
Address 6115 0
MAPrc
Level 4, 607 St Kilda Road,
Melbourne, Victoria
3004
Country 6115 0
Australia
Phone 6115 0
+61 3 9076 6552
Fax 6115 0
Email 6115 0
paul.fitzgerald@monash.edu

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary