Treatment Resistant DepressionTMSNCT01677078
Coupling Repetitive Transcranial Magnetic Stimulation With a Neuronavigation System in Treatment Resistant Depression
A study testing Neuronavigation system and Standard localisation method in people with Treatment Resistant Depression, run by Rennes University Hospital at 5 sites in France.
Trial summary
Repetitive Transcranial Magnetic Stimulation (rTMS) is a non invasive technique which was shown to be effective in the treatment of major depression. The dorsolateral prefrontal cortex (DLPFC) is the anatomic target in rTMS studies and the standard (manual) '5-cm method' for positioning the coil over DLPFC is the… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Treatment Resistant Depression
- What is being tested?
- Neuronavigation system and Standard localisation method
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 107 participants
- Where
- 5 sitesFrance
- Study dates
- 21 Jan 2013to 25 Mar 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients giving their consent;
- Right handed;
- Age > 18 and < 65;
- With a DSM-IV diagnosis of MDD, single episode or recurrent;
- With an antidepressant treatment unchanged in the 3 last weeks;
- With an MADRS score ≥ 21;
- Benzodiazepine treatments have to be avoided;
Who cannot join
- Major depressive episode with psychotic characteristics;
- A lifetime of the following axis 1 diagnoses: schizophrenia or substance use disorder (alcohol or other substance);
- Stade 5 of Thase and Rush classification ;
- Involuntary hospitalizations;
- Patients under guardianship;
- Outpatients in case of an increased risk of suicide as assessed by a MADRS item 10 > 3;
- Contraindication for MRI or rTMS: a personal history of a seizure disorder, presence of neurologic or neurosurgical disorder, presence of ferromagnetic material (including intraocular) or metallic medical devices (pacemakers);
- Pregnancy.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
France5 sites
Centre Santé Mentale Angevin CESAME
Angers, 49130
CHU de Brest
Brest, 29200
Etablissement Public de Santé Mentale
Quimperlé, 29300
CHGR
Rennes, 35000
EPSM Morbihan
Saint-Avé, 56890
About this study
Official title: Assessment of the Neuronavigation System Coupled With Repetitive Transcranial Magnetic Stimulation. A Randomized Double Blind Study
Repetitive Transcranial Magnetic Stimulation (rTMS) is a non invasive technique which was shown to be effective in the treatment of major depression.
The dorsolateral prefrontal cortex (DLPFC) is the anatomic target in rTMS studies and the standard (manual) '5-cm method' for positioning the coil over DLPFC is the reference. Nevertheless, it has been criticized due to poor targeting accuracies attributed to inter-subject variability.
Read more
Such an inaccuracy could have any therapeutic consequences as a decrease in rTMS efficacy.
Preliminary findings suggest that a more reproductible and accurate method, based upon a neuronavigation system could allow for a better efficacy. This finding has to be replicated with sound methodology.
Investigator's objective is to compare efficacy on mood of coil positioning based upon a neuronavigation device versus coil positioning based upon the standard method.
Read the detailed description
Background :
Repetitive Transcranial Magnetic Stimulation (rTMS) is a new tool for major depressive disorder.
rTMS is a non invasive technique allowing for a localized stimulation of cerebral tissue cortex. rTMS uses electromagnetic induction to induce weak electric currents using a rapidly changing magnetic field; this can modify activity in specific or general parts of the brain.
Meta-analyses have stated that rTMS appeared to be effective in the treatment of major depression despite any limits concerning sample sizes and methodological concerns.
Studies have shown that this technique potentiates antidepressants treatment in combination therapy.
It has received FDA approval for the management of major depressive disorder. Stimulation parameters are numerous (frequency, intensity, number of pulses) and their effects are increasingly better understood in order to predict a better balance between efficacy and tolerability.
The dorsolateral prefrontal cortex (DLPFC) is the target in repetitive transcranial magnetic stimulation and the standard (manual) '5-cm method' for positioning the transcranial magnetic stimulation coil over DLPFC is the reference. It has been criticized due to poor targeting accuracies attributed to inter-subject variability.
Such an inaccuracy could have consequences as a decrease in rTMS efficacy. Any preliminary findings suggest that a more reproductible and accurate method, based upon a neuronavigation system could allow for a better efficacy. This finding has to be replicated with sound methodology.
Objectives:
To compare efficacy on mood of coil positioning based upon a neuronavigation device versus coil positioning based upon the standard method.
Investigators hypothesized that an accurate localization and stimulation of DLPFC using neuronavigation would be more effective than the less accurate standard method.
A secondary objective is to compare the efficacy on patient's self perception, on psychomotor symptoms and the tolerability of the two methods.
- Conditions
- Treatment Resistant Depression
- Being tested
- Neuronavigation system, Standard localisation method
- Keywords
- Major depressive disorder, rTMS, Neuronavigation
- Medical subject headings
- Depressive Disorder, Treatment-Resistant, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neuronavigation systemDevice
Also called Syneika One (Syneika, France)
Neuronavigation
Standard localisation methodDevice
Manual localisation of the DLPFC using the standard localisation method (i.e. the '5-cm method')
| Study group | Role | What they receive |
|---|---|---|
| Neuronavigation system | Experimental | 10 sessions of rTMS coupled with a neuronavigation system
Description of 1 session of the rTMS protocol :
* Frequency: 20Hz
* Intensity: 110% of motor threshold
* 80 train of 2 seconds duration
* 10 seconds between two trains
* 3200 pulses
Devices :
* rTMS: System Mag Pro (Magventure, Denmark)
* Neuronavigation system: Syneika One (Syneika, France) Receives: Device: Neuronavigation system |
| Standard localisation method | Sham comparator | 10 sessions of rTMS with manual localisation of the DLPFC using the standard localisation method (i.e. the '5-cm method')
Description of 1 session of the rTMS protocol :
* Frequency: 20Hz
* Intensity: 110% of motor threshold
* 80 train of 2 seconds duration
* 10 seconds between two trains
* 3200 pulses
Devices :
- rTMS: System Mag Pro (Magventure, Denmark) Receives: Device: Standard localisation method |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response
Response defined as at least 50% reduction in the MADRS score.
Measured: Day 44
Secondary outcomes (5)
Response
Response is defined as at least 50% reduction in the MADRS score.
Measured: Day 14
Remission
Remission is defined as a MADRS score ≤ 8.
Measured: Day 14 Day 44
MADRS
Description: It is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders.
Measured: Day 0, day 14 and day 44
BDI
It is a multiple-choice self-report inventory and one of the most widely used instruments for measuring the severity of depression.
Measured: Day 0 Day 14 Day 14
ERD
It is a 14-item questionnaire which psychiatrists use to measure the intensity of motor retardation.
Measured: Day 0 Day 14 day 44
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2012 (estimated)
- Study start21 Jan 2013
- Primary completion25 Mar 2017
- Study completion25 Mar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Treatment Resistant DepressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 107 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rennes University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Bruno Millet, MD PhD, Principal investigator, Rennes University HospitalJean Michel Reymann, PhD, Study chair, Rennes University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01677078
- Sponsor's protocol ID
- 2011-A01272-39
- Acronym
- TMS
- Status last verified
- Aug 2018
- First submitted
- 29 Aug 2012
- Last updated
- 31 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Millet B, Harika-Germaneau G, Maatoug R, Naudet F, Reymann JM, Turmel V, Batail JM, Soulabaille J, Jaafari N, Drapier D. Repetitive Transcranial Magnetic Stimulation targeted with MRI based neuro-navigation in major depressive episode: a double-blind, multicenter randomized controlled trial. PLoS One. 2025 May 27;20(5):e0317597. doi: 10.1371/journal.pone.0317597. eCollection 2025.
PubMed 40424301
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of the Neuronavigation System Coupled With Repetitive Transcranial Magnetic Stimulation. A Randomized Double Blind Study
- ClinicalTrials.gov ID
- NCT01677078
- Acronym / sponsor ID
- TMS / 2011-A01272-39
- Conditions
- Treatment Resistant Depression
- Keywords
- Major depressive disorder, rTMS, Neuronavigation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 107 participants (actual)
- Lead sponsor
- Rennes University HospitalUniversity, hospital or other
- Study start
- 21 Jan 2013 (actual)
- Primary completion
- 25 Mar 2017 (actual)
- Study completion
- 25 Mar 2017 (actual)
- First posted
- 31 Aug 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Repetitive Transcranial Magnetic Stimulation (rTMS) is a non invasive technique which was shown to be effective in the treatment of major depression.
The dorsolateral prefrontal cortex (DLPFC) is the anatomic target in rTMS studies and the standard (manual) '5-cm method' for positioning the coil over DLPFC is the reference. Nevertheless, it has been criticized due to poor targeting accuracies attributed to inter-subject variability.
Such an inaccuracy could have any therapeutic consequences as a decrease in rTMS efficacy.
Preliminary findings suggest that a more reproductible and accurate method, based upon a neuronavigation system could allow for a better efficacy. This finding has to be replicated with sound methodology.
Investigator's objective is to compare efficacy on mood of coil positioning based upon a neuronavigation device versus coil positioning based upon the standard method.
Detailed description
Background :
Repetitive Transcranial Magnetic Stimulation (rTMS) is a new tool for major depressive disorder.
rTMS is a non invasive technique allowing for a localized stimulation of cerebral tissue cortex. rTMS uses electromagnetic induction to induce weak electric currents using a rapidly changing magnetic field; this can modify activity in specific or general parts of the brain.
Meta-analyses have stated that rTMS appeared to be effective in the treatment of major depression despite any limits concerning sample sizes and methodological concerns.
Studies have shown that this technique potentiates antidepressants treatment in combination therapy.
It has received FDA approval for the management of major depressive disorder. Stimulation parameters are numerous (frequency, intensity, number of pulses) and their effects are increasingly better understood in order to predict a better balance between efficacy and tolerability.
The dorsolateral prefrontal cortex (DLPFC) is the target in repetitive transcranial magnetic stimulation and the standard (manual) '5-cm method' for positioning the transcranial magnetic stimulation coil over DLPFC is the reference. It has been criticized due to poor targeting accuracies attributed to inter-subject variability.
Such an inaccuracy could have consequences as a decrease in rTMS efficacy. Any preliminary findings suggest that a more reproductible and accurate method, based upon a neuronavigation system could allow for a better efficacy. This finding has to be replicated with sound methodology.
Objectives:
To compare efficacy on mood of coil positioning based upon a neuronavigation device versus coil positioning based upon the standard method.
Investigators hypothesized that an accurate localization and stimulation of DLPFC using neuronavigation would be more effective than the less accurate standard method.
A secondary objective is to compare the efficacy on patient's self perception, on psychomotor symptoms and the tolerability of the two methods.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Neuronavigation system | Experimental | Device: Neuronavigation system10 sessions of rTMS coupled with a neuronavigation system Description of 1 session of the rTMS protocol : * Frequency: 20Hz * Intensity: 110% of motor threshold * 80 train of 2 seconds duration * 10 seconds between two trains * 3200 pulses Devices : * rTMS: System Mag Pro (Magventure, Denmark) * Neuronavigation system: Syneika One (Syneika, France) |
| Standard localisation method | Sham comparator | Device: Standard localisation method10 sessions of rTMS with manual localisation of the DLPFC using the standard localisation method (i.e. the '5-cm method') Description of 1 session of the rTMS protocol : * Frequency: 20Hz * Intensity: 110% of motor threshold * 80 train of 2 seconds duration * 10 seconds between two trains * 3200 pulses Devices : - rTMS: System Mag Pro (Magventure, Denmark) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients giving their consent;
- Right handed;
- Age > 18 and < 65;
- With a DSM-IV diagnosis of MDD, single episode or recurrent;
- With an antidepressant treatment unchanged in the 3 last weeks;
Key exclusion criteria (8 listed)
- Major depressive episode with psychotic characteristics;
- A lifetime of the following axis 1 diagnoses: schizophrenia or substance use disorder (alcohol or other substance);
- Stade 5 of Thase and Rush classification ;
- Involuntary hospitalizations;
- Patients under guardianship;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Neuronavigation systemAlso: Syneika One (Syneika, France)Neuronavigation | Device | Neuronavigation system |
| Standard localisation methodManual localisation of the DLPFC using the standard localisation method (i.e. the '5-cm method') | Device | Standard localisation method |
Primary outcome
Response
Time frame: Day 44
Response defined as at least 50% reduction in the MADRS score.
5 secondary outcomes
Response
Time frame: Day 14
Remission
Time frame: Day 14 Day 44
MADRS
Time frame: Day 0, day 14 and day 44
BDI
Time frame: Day 0 Day 14 Day 14
ERD
Time frame: Day 0 Day 14 day 44
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2018.
- Derived from this study: PubMed 40424301Millet B, Harika-Germaneau G, Maatoug R, Naudet F, Reymann JM, Turmel V, Batail JM, Soulabaille J, Jaafari N, Drapier D. Repetitive Transcranial Magnetic Stimulation targeted with MRI based neuro-navigation in major depressive episode: a double-blind, multicenter randomized controlled trial. PLoS One. 2025 May 27;20(5):e0317597. doi: 10.1371/journal.pone.0317597. eCollection 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bruno Millet, MD PhD principal investigator
Rennes University Hospital
Jean Michel Reymann, PhD study chair
Rennes University Hospital
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Neuronavigation system and Standard localisation method in people with Treatment Resistant Depression, run by Rennes University Hospital at 5 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response (time frame: Day 44). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01677078, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2018.