Treatment Resistant DepressionOLDEP-TBSNCT07188753
Randomized Controlled Trial Testing the Efficacy of Transcranial Magnetic Stimulation by Accelerated & High-dose Theta-burst, Functional Imaging Guided, in the Treatment of Depression in Elderly Subjects With Cognitive Impairment
A study testing transcranial magnetic stimulation by accelerated & high-dose theta-burst, functional imaging guided, i in people with Treatment Resistant Depression and Elderly Depression (≥65y.o.), run by Rennes University Hospital.
Trial summary
This trial aims at testing a new intensive, personalized functional targeting, transcranial magnetic stimulation technique for elderly patients (aged ≥ 65 years) suffering from a current treatment resistant depressive episode to at least one antidepressant, and suffering from significant secondary cognitive… Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Treatment Resistant Depression, Elderly Depression (≥65y.o.)
- What is being tested?
- transcranial magnetic stimulation by accelerated & high-dose theta-burst, functional imaging guided, i
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 186 participants
- Where
- No sites listed yet
- Study dates
- 15 Dec 2025to 15 Dec 2031
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Male or female, of ages ≥ 65 years at the time of screening
- Currently diagnosed with either Major Depressive Disorder (MDD) and meets criteria for a current Major Depressive Episode (MDE) according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5).
- Patients that don't meet the treatment response criteria according to antidepressant treatment history form (ATHF) for whom a switch to another ATD is required.
- rTMS/iTBS naïve.
- Access to ongoing psychiatric care before and after completion of the study.
- Access to clinical rTMS after completion of the study.
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- In good general health, as evidenced by medical history (i.e. any ongoing serious and vital medical condition).
- Having signed a free, informed and written consent
- Patients that have a valid health insurance and are affiliated to or beneficiary of a social security system.
- Montgomery and Asberg Depression Rating Scale (MADRS) score of ≥ 20 at screening.
- MoCA total score ≤ 26.
- Comply with eligibility criteria checklist (Appendix 3)
Who cannot join
- Major cognitive disorder according to DSM-5 criteria.
- The presence or diagnosis of prominent (primary) anxiety disorder, personality disorder, or dysthymia.
- Bipolar Affective Disorder I \& II and primary psychotic disorders.
- Autism Spectrum disorder or Intellectual Disability.
- A diagnosis of obsessive-compulsive disorder (OCD).
- Current moderate or severe substance use disorder (according to DSM-5 criteria) or demonstrating signs of acute substance withdrawal.
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- Any history of ECT (greater than 8 sessions) without meeting response criteria.
- No recent (during the current depressive episode) or concurrent use of a rapid acting antidepressant agent (i.e., ketamine or a course of ECT).
- History of significant neurologic disease, including Parkinson's or Huntington's disease, brain tumor, unexpected seizure/epilepsy disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma (having caused a coma and/or requiring specific hospital care, and/or with abnormal brain imaging).
- Untreated or insufficiently treated dysthyroidism (TSH range 0.4-4mUI/l).
- Treatment with another investigational drug or other intervention within the study period.
- Any other condition deemed by the PI to interfere with the study or increase risk to the participant.
- Contraindications to receiving rTMS (e.g., metal in head, history of seizure, known brain lesion).
- Contraindications to Magnetic Resonance Imaging (MRI) (ferromagnetic metal in their body).
- Participants taking certain psychoactive medications will be assessed for safety by the PI, due to potential for increase of seizure risk (e.g., clozapine) and change in cortical excitability (e.g. anticonvulsant, benzodiazepines). A maximum daily dose of 2mg lorazepam equivalent will be accepted.
- Persons referred in articles L.1121-5 to L.1121-8 and L.1122-2 of the Public Health Code: Pregnant women, women in labour and breastfeeding mothers Person deprived of liberty for judicial or administrative decision, adult person under legal protection (any form of public guardianship).
- Mini Mental Status Examination (MMSE) score < 21.
- Current severe insomnia (must sleep a minimum of 5 hours each night before stimulation).
- Current mania or psychosis.
- Endorses clinically significant explicit suicidal cognitions (score ≥ 6 on the Beck Suicide Scale [BSS] self-report).
- Any current substance abuse that is clinically elicited or based on urine/breathalyzer screening deemed by the PI to be critical from a safety standpoint.
- Depth-adjusted aiTBS treatment dose > 65% maximum stimulator output (MSO).
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: OLDEP-TBS - Randomized Controlled Trial Testing the Efficacy of Transcranial Magnetic Stimulation by Accelerated & High-dose Theta-burst, Functional Imaging Guided, in the Treatment of Depression in Elderly Subjects With Cognitive Impairment
This trial aims at testing a new intensive, personalized functional targeting, transcranial magnetic stimulation technique for elderly patients (aged ≥ 65 years) suffering from a current treatment resistant depressive episode to at least one antidepressant, and suffering from significant secondary cognitive impairment.
The intervention will be based on an accelerated neuromodulation technique using intermittent theta bursts (aiTBS) guided by a personalised funcitonal target within the left dorsolateral prefrontal cortex (DLPFC), using the SAINT® technology, which was recently cleared by the FDA.
Read the detailed description
Depression in older adults is often associated with cognitive impairment. Executive dysfunction exposes patients to poor response to antidepressants, increased risk of relapse and suicide, and greater disability. Depression doubles the risk of developing dementia in later life.
Late-onset depression is considered more difficult to treat due to low tolerance to standard antidepressant treatments, which prevents dose optimisation. Late-onset depression is considered more difficult to treat due to poor tolerance to standard antidepressant treatments, which prevents dose optimisation.
Furthermore, antidepressants are not optimal for improving cognitive function. Thus, antidepressant therapies are limited in terms of efficacy or tolerance, leading to persistent depressive symptoms and cognitive deficits that impact daily functioning, quality of life, and even independence.
Transcranial magnetic stimulation, a focused non-pharmacological antidepressant therapy, is a promising alternative. Several meta-analyses have demonstrated its efficacy as an antidepressant treatment and its potential for treating mild cognitive impairment. However, these studies have encountered certain limitations, such as small sample sizes and heterogeneity. Recently, a randomised controlled trial testing an accelerated form of intermittent theta burst stimulation (aiTBS) in adults with treatment-resistant depression demonstrated a high remission rate of approximately 80% (with effect sizes ranging from [1.4-1.8]). This technique has a good tolerance profile.
Overall, aiTBS treatment has several potentially beneficial aspects for depression in older adults: efficacy, rapid onset of action, and good tolerability. Such a technique could prevent the negative impact of depression and cognitive impairment on the quality of life and independence of older adults with depression.
In this randomised controlled trial (RCT), the investigators aim to test the efficacy of aiTBS treatment guided by functional connectivity at rest in elderly patients suffering from major depressive disorder (MDD) in a major depressive episode (MDE) and cognitive impairment. The investigators hypothesise that active aiTBS treatment will be superior to placebo aiTBS treatment in improving depressive and cognitive symptoms.
- Being tested
- transcranial magnetic stimulation by accelerated & high-dose theta-burst, functional imaging guided, i
- Keywords
- transcranial magentic stimulation, personalized targeting, depression, elderly, old-age depression, treatment resistant, accelerated TMS, iTBS, theta birst stimulation
- Medical subject headings
- Depressive Disorder, Treatment-Resistant, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
transcranial magnetic stimulation by accelerated & high-dose theta-burst, functional imaging guided, iOther
Participants will then be treated with 1,800 pulses of iTBS (3-pulse 50-Hz bursts at 5-Hz for 2-second trains, with trains every 10 seconds) per session at 90% resting motor threshold and depth-adjustment to the personalized functional target. Each session will last 10 min followed by a 50-minute intersession interval. Ten sessions will be applied per day (18,000 pulses/day) for 5 consecutive days (90,000 total pulses).
| Study group | Role | What they receive |
|---|---|---|
| Interventional Group | Experimental | active transcranial magnetic stimulation using accelerated (aiTBS) Receives: Other: transcranial magnetic stimulation by accelerated & high-dose theta-burst, functional imaging guided, i |
| Control group | Placebo comparator | Placebo transcranial magnetic stimulation (Sham stimulation) Receives: Other: transcranial magnetic stimulation by accelerated & high-dose theta-burst, functional imaging guided, i |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the effect of aiTBS, as compared to sham stimulation, on depressive symptoms at one-month visit (35+/-3 days after the last day of treatment).
Montgomery and Asberg Depression Rating Scale (MADRS) (min:0 / max:60)
Measured: at one-month visit (35+/-3 days after the last day of treatment)
Secondary outcomes (5)
To determine the effect of aiTBS, as compared to sham stimulation on depressive symptoms at two-month post-intervention
Montgomery and Asberg Depression Rating Scale (MADRS) (min:0 / max:60)
Measured: at two-month post-intervention (F+65D (+/-3D) after the last day of treatment).
To determine the effect of aiTBS, as compared to sham stimulation
Montgomery and Asberg Depression Rating Scale (MADRS) (min:0 / max:60)
Measured: at six-month post-intervention (F+180D(+/-6D) after the last day of treatment)
To determine the effect of aiTBS, as compared to sham stimulation
MATTIS (global cognitive functioning) score
Measured: at one month post-intervention (+35D (+/-3D) after the last day of treatment).
To determine the effect of aiTBS, as compared to sham stimulation
MATTIS (global cognitive functioning) score
Measured: at two-month post-intervention (F+65D (+/-3D) after the last day of treatment)
To determine the effect of aiTBS, as compared to sham stimulation on global cognitive functioning, at six-month post-intervention visit.
MATTIS (global cognitive functioning) score
Measured: at six-month post-intervention(F+180D(+/-6D) after the last day of treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2025
- Study start15 Dec 2025 (estimated)
- Primary completion15 Jun 2031 (estimated)
- Study completion15 Dec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Treatment Resistant DepressionStudies of the same condition, open and under way.
- More trials run by Rennes University HospitalThe sponsor's other registered studies.
- 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 186 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rennes University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jean-Marie BATAIL, M.D.,Ph.D., Principal investigator, C. H. GUILLAUME REGNIER RENNESBruno MILLET, PH-PD, Principal investigator, APHP- LA PITIEGhina HARIKA GERMANEAU, MD, Principal investigator, Centre Hospitalier Henri LaboritMaud ROTHARMEL, MD, Principal investigator, CHS DU ROUVRAY SOTTEVILLE-LES-ROUENSamuel BULTEAU, MD, Principal investigator, Nantes University HospitalNoomane BOUAZIZ, MD, Principal investigator, EPS VILLE EVRARDMoussa CHALAH, MD, Principal investigator, GHU PARISDavid SZEKELY, MD, Principal investigator, Centre Hospitalier Princesse Grace
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07188753
- Sponsor's protocol ID
- 35RC22_9819_OLDEP-TBS
- Acronym
- OLDEP-TBS
- Status last verified
- Sep 2025
- First submitted
- 16 Sep 2025
- Last updated
- 23 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- OLDEP-TBS - Randomized Controlled Trial Testing the Efficacy of Transcranial Magnetic Stimulation by Accelerated & High-dose Theta-burst, Functional Imaging Guided, in the Treatment of Depression in Elderly Subjects With Cognitive Impairment
- ClinicalTrials.gov ID
- NCT07188753
- Acronym / sponsor ID
- OLDEP-TBS / 35RC22_9819_OLDEP-TBS
- Keywords
- transcranial magentic stimulation, personalized targeting, depression, elderly, old-age depression, treatment resistant, accelerated TMS, iTBS
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 186 participants (estimated)
- Lead sponsor
- Rennes University HospitalUniversity, hospital or other
- Study start
- 15 Dec 2025 (estimated)
- Primary completion
- 15 Jun 2031 (estimated)
- Study completion
- 15 Dec 2031 (estimated)
- First posted
- 23 Sep 2025 (actual)
- 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.
This trial aims at testing a new intensive, personalized functional targeting, transcranial magnetic stimulation technique for elderly patients (aged ≥ 65 years) suffering from a current treatment resistant depressive episode to at least one antidepressant, and suffering from significant secondary cognitive impairment.
The intervention will be based on an accelerated neuromodulation technique using intermittent theta bursts (aiTBS) guided by a personalised funcitonal target within the left dorsolateral prefrontal cortex (DLPFC), using the SAINT® technology, which was recently cleared by the FDA.
Detailed description
Depression in older adults is often associated with cognitive impairment. Executive dysfunction exposes patients to poor response to antidepressants, increased risk of relapse and suicide, and greater disability. Depression doubles the risk of developing dementia in later life.
Late-onset depression is considered more difficult to treat due to low tolerance to standard antidepressant treatments, which prevents dose optimisation. Late-onset depression is considered more difficult to treat due to poor tolerance to standard antidepressant treatments, which prevents dose optimisation.
Furthermore, antidepressants are not optimal for improving cognitive function. Thus, antidepressant therapies are limited in terms of efficacy or tolerance, leading to persistent depressive symptoms and cognitive deficits that impact daily functioning, quality of life, and even independence.
Transcranial magnetic stimulation, a focused non-pharmacological antidepressant therapy, is a promising alternative. Several meta-analyses have demonstrated its efficacy as an antidepressant treatment and its potential for treating mild cognitive impairment. However, these studies have encountered certain limitations, such as small sample sizes and heterogeneity. Recently, a randomised controlled trial testing an accelerated form of intermittent theta burst stimulation (aiTBS) in adults with treatment-resistant depression demonstrated a high remission rate of approximately 80% (with effect sizes ranging from [1.4-1.8]). This technique has a good tolerance profile.
Overall, aiTBS treatment has several potentially beneficial aspects for depression in older adults: efficacy, rapid onset of action, and good tolerability. Such a technique could prevent the negative impact of depression and cognitive impairment on the quality of life and independence of older adults with depression.
In this randomised controlled trial (RCT), the investigators aim to test the efficacy of aiTBS treatment guided by functional connectivity at rest in elderly patients suffering from major depressive disorder (MDD) in a major depressive episode (MDE) and cognitive impairment. The investigators hypothesise that active aiTBS treatment will be superior to placebo aiTBS treatment in improving depressive and cognitive symptoms.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Interventional Group | Experimental | Other: transcranial magnetic stimulation by accelerated & high-dose theta-burst, functional imaging guided, iactive transcranial magnetic stimulation using accelerated (aiTBS) |
| Control group | Placebo comparator | Other: transcranial magnetic stimulation by accelerated & high-dose theta-burst, functional imaging guided, iPlacebo transcranial magnetic stimulation (Sham stimulation) |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (12 listed)
- Male or female, of ages ≥ 65 years at the time of screening
- Currently diagnosed with either Major Depressive Disorder (MDD) and meets criteria for a current Major Depressive Episode (MDE) according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5).
- Patients that don't meet the treatment response criteria according to antidepressant treatment history form (ATHF) for whom a switch to another ATD is required.
- rTMS/iTBS naïve.
- Access to ongoing psychiatric care before and after completion of the study.
Key exclusion criteria (22 listed)
- Major cognitive disorder according to DSM-5 criteria.
- The presence or diagnosis of prominent (primary) anxiety disorder, personality disorder, or dysthymia.
- Bipolar Affective Disorder I \& II and primary psychotic disorders.
- Autism Spectrum disorder or Intellectual Disability.
- A diagnosis of obsessive-compulsive disorder (OCD).
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 |
|---|---|---|
| transcranial magnetic stimulation by accelerated & high-dose theta-burst, functional imaging guided, iParticipants will then be treated with 1,800 pulses of iTBS (3-pulse 50-Hz bursts at 5-Hz for 2-second trains, with trains every 10 seconds) per session at 90% resting motor threshold and depth-adjustment to the personalized functional target. Each session will last 10 min followed by a 50-minute intersession interval. Ten sessions will be applied per day (18,000 pulses/day) for 5 consecutive days (90,000 total pulses). | Other | Control group, Interventional Group |
Primary outcome
To determine the effect of aiTBS, as compared to sham stimulation, on depressive symptoms at one-month visit (35+/-3 days after the last day of treatment).
Time frame: at one-month visit (35+/-3 days after the last day of treatment)
Montgomery and Asberg Depression Rating Scale (MADRS) (min:0 / max:60)
5 secondary outcomes
To determine the effect of aiTBS, as compared to sham stimulation on depressive symptoms at two-month post-intervention
Time frame: at two-month post-intervention (F+65D (+/-3D) after the last day of treatment).
To determine the effect of aiTBS, as compared to sham stimulation
Time frame: at six-month post-intervention (F+180D(+/-6D) after the last day of treatment)
To determine the effect of aiTBS, as compared to sham stimulation
Time frame: at one month post-intervention (+35D (+/-3D) after the last day of treatment).
To determine the effect of aiTBS, as compared to sham stimulation
Time frame: at two-month post-intervention (F+65D (+/-3D) after the last day of treatment)
To determine the effect of aiTBS, as compared to sham stimulation on global cognitive functioning, at six-month post-intervention visit.
Time frame: at six-month post-intervention(F+180D(+/-6D) after the last day of treatment)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 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.
Jean-Marie BATAIL, M.D.,Ph.D. principal investigator
C. H. GUILLAUME REGNIER RENNES
Bruno MILLET, PH-PD principal investigator
APHP- LA PITIE
Ghina HARIKA GERMANEAU, MD principal investigator
Centre Hospitalier Henri Laborit
Questions about this trial
What is this clinical trial studying?
A study testing transcranial magnetic stimulation by accelerated & high-dose theta-burst, functional imaging guided, i in people with Treatment Resistant Depression and Elderly Depression (≥65y.o.), run by Rennes University Hospital.
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 12 inclusion and 22 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: opening soon, as of the sponsor's last update on 23 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jean-Marie BATAIL, M.D.,Ph.D. (0299333937, jm.batail@ch-guillaumeregnier.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the effect of aiTBS, as compared to sham stimulation, on depressive symptoms at one-month visit (35+/-3 days after the last day of treatment). (time frame: at one-month visit (35+/-3 days after the last day of treatment)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Sep 2025.