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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00402220




Registration number
NCT00402220
Ethics application status
Date submitted
18/11/2006
Date registered
22/11/2006
Date last updated
31/10/2007

Titles & IDs
Public title
A Double-Blind Sham Controlled Trial of rTMS in Treatment Resistant Major Depression
Scientific title
A Double-Blind Sham Controlled Trial of rTMS in Treatment Resistant Major Depression
Secondary ID [1] 0 0
fitzgeraldp
Universal Trial Number (UTN)
Trial acronym
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - TMS
Treatment: Devices - Sham TMS

Active Comparator: 1 - active TMS

Placebo Comparator: 2 - Sham TMS


Treatment: Drugs: TMS
Active Transcranial Magnetic Stimulation

Treatment: Devices: Sham TMS
Sham Transcranial Magnetic Stimulation

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Devices
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The 17- item Hamilton Rating Scale for Depression (HAM-D)
Timepoint [1] 0 0
every 3 weeks

Eligibility
Key inclusion criteria
Patients will be included if they:

1. Have a DSM-IV diagnosis of a major depressive episode (SCID 11).

2. Aged 18-85.

3. Have treatment resistant depression at Stage II of the Thase and Rush classification
[31]; .e. have failed to achieve a clinical response, or did not tolerate, at least
two separate antidepressant trials of sufficient dose for at least 6 weeks.

4. Have a Hamilton Depression Rating Scale Score of > 20 (moderate - severe depression).
Including only a severely ill group of subjects limits the placebo response rate [32].
Moreover, this will allow us to address the application of rTMS methods in the most
clinically relevant subgroup of patients (in addition helping to constrain group
heterogeneity, a major issue in depression research).

5. 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
85 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients who have an unstable medical condition, neurological disorder or any history
of a seizure disorder or are currently pregnant or lactating.

2. In the opinion of the investigator, are a sufficient suicidal risk to require
immediate electro-convulsive therapy.

3. 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.

Please note: several of these criteria (e.g. inclusion criteria 1 & 2, exclusion criteria
3) have been selected to explicitly constrain the heterogeneity of the sample to increase
the likely power of the study to detect differences between the groups given the
potentially subtle difference between the treatment methods.

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
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
Not Applicable
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Unknown status
Data analysis
Reason for early stopping/withdrawal
Other reasons
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
Recruitment hospital [1] 0 0
Alfred Psychiatry Research Centre - Prahran
Recruitment postcode(s) [1] 0 0
3181 - Prahran

Funding & Sponsors
Primary sponsor type
Other
Name
Bayside Health
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
National Health and Medical Research Council, Australia
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The main treatment option for Treatment Resistant Depression is electroconvulsive therapy
(ECT) which is often effective but complicated by cognitive side effects, need for
anaesthesia and considerable stigma.

In recent years considerable efforts have been made to increase public awareness about
depression and increase access to services. However, the increasing number of patients
accessing treatment for depression in clinical services is also likely to be accompanied by a
sizeable increase in the number of patients with TRD. Despite the demand, relatively few
treatment options are available to such patients. One of the only substantially new
treatments developed for TRD in recent years has been the advent of repetitive transcranial
magnetic stimulation (rTMS). Repetitive TMS has been evaluated in over 20 trials conducted
over the last 10 years. Previous research indicates that rTMS has antidepressant activity;
however, the proportion of patients who respond to rTMS and the degree of treatment response
demonstrated in trials to date is limited. The limitations of these studies include
relatively small samples and limited duration of treatment (i.e., 2 weeks) as well as a lack
of long term follow-up. As rTMS is gradually entering use in routine clinical practice (for
example, recent regulation of its use in Canada), research is urgently required to establish
ways to enhance treatment response both in regards to the extent of response within
individuals and the proportion of individuals in whom rTMS has effects.

Stimulation site is another important treatment factor; thus far almost all of the trials of
rTMS in TRD conducted have evaluated the utility of high frequency left prefrontal cortex
(PFC) rTMS (HFL-TMS). In addition, several studies have evaluated the treatment efficacy of
low frequency rTMS to right PFC (LFR-TMS). In a previously published study we have
demonstrated that these two approaches have similar therapeutic benefit and both were
superior to sham stimulation.

A promising new approach to enhance efficacy involves combining LFR-TMS and HFL-TMS in a
sequential manner. We describe this as sequential bilateral rTMS (SB-rTMS). We have recently
published the results of the first substantial evaluation of SB-rTMS showing not only a
superiority to placebo in TRD but also a therapeutic response that is substantially superior
to response rates in most of the published studies of unilateral rTMS (>50% of patients
achieving standard criteria for clinical response compared to usually <30% in most studies).
In this proposed research study, we will directly test the hypothesis that SB-rTMS produces a
greater therapeutic response than HFL-TMS and compare both of these forms of stimulation to
placebo (i.e., sham) stimulation.
Trial website
https://clinicaltrials.gov/show/NCT00402220
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Paul B Fitzgerald, MBBS, MPM, PhD, FRANZCP
Address 0 0
Alfred Psychiatry Research Centre
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Paul B Fitzgerald, MBBS, MPM, PhD, FRANZCP
Address 0 0
Country 0 0
Phone 0 0
9276 6564
Fax 0 0
Email 0 0
p.fitzgerald@alfred.com.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT00402220