Treatment Resistant DepressionStimulUSNCT06085950
Transcranial Ultrasonic Stimulation in Treatment-resistant Depression : an Open-label Pilot Trial
A study testing Transcranial Ultrasonic Stimulation prototype in people with Treatment Resistant Depression, run by Centre Hospitalier St Anne at 1 site in France.
Trial summary
The primary objective of this study is to optimize the protocol for the TUS administration in patients with TRD while gaining an initial impression of treatment efficacy. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Treatment Resistant Depression
- What is being tested?
- Transcranial Ultrasonic Stimulation prototype
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteFrance
- Study dates
- 9 May 2023to Jun 2028
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age between 18 and 75 years,
- Diagnosis of major depressive episode (MDE) as part of major depressive disorder as defined by DSM-5 criteria
- Severe MDE (HDRS-17> 20)
- Drug resistance to at least two well-conducted antidepressant treatment lines
- With stable antidepressant treatment for at least 4 weeks before inclusion
- Benefiting from a social security scheme
- Having given their consent to participate
Who cannot join
- Psychiatric history other than a mood disorder
- Neurological history, including epilepsy and intracerebral calcifications
- History of substance use disorder other than tobacco
- Contraindication to brain MRI (pacemaker, neurostimulator, injury from metallic shine, …)
- Compulsory psychiatric care
- Protected adults, people under legal safeguard
- Pregnant or breastfeeding woman
- Women of childbearing age who do not have a negative pregnancy test and are not using contraception
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
David ATTALI contact
France1 site, 1 recruiting
- Recruiting
GHU Sainte-Anne
Paris, 75014
Marion Plaze, MD, PHD, 0145658720, m.plaze@ghu-paris.fr
David ATTALI, MD, PHD, d.attali@ghu-paris.fr
About this study
Official title: Transcranial Ultrasonic Stimulation in Treatment-resistant Depression: an Open-label Pilot Trial
The primary objective of this study is to optimize the protocol for the TUS administration in patients with TRD while gaining an initial impression of treatment efficacy.
- Conditions
- Treatment Resistant Depression
- Being tested
- Transcranial Ultrasonic Stimulation prototype
- Medical subject headings
- Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial Ultrasonic Stimulation prototypeDevice
Transcranial Ultrasonic Stimulation prototype delivers personalized low-intensity ultrasound stimulation
| Study group | Role | What they receive |
|---|---|---|
| TUS - 5 min sessions, 5% duty cycle, 5 sessions/day (n=5) | Experimental | Low-intensity transcranial focused ultrasound stimulation of deep brain target, using a personalized acoustic lens to correct the aberrations induced by the skull. Sessions of 5 minutes at a 5% duty cycle, delivered 5 times per day for 5 days (25 sessions total). Receives: Device: Transcranial Ultrasonic Stimulation prototype |
| TUS - 40 min sessions, 5% duty cycle, 2 sessions/day (n=7) | Experimental | Low-intensity transcranial focused ultrasound stimulation of deep brain target, using a personalized acoustic lens to correct the aberrations induced by the skull. Sessions of 40 minutes at a 5% duty cycle, delivered 2 times per day for 5 days (10 sessions total). Receives: Device: Transcranial Ultrasonic Stimulation prototype |
| TUS - 40 min sessions, 1% duty cycle, increased acoustic power, 2 sessions/day (n=10) | Experimental | Low-intensity transcranial focused ultrasound stimulation of deep brain target, using a personalized acoustic lens to correct the aberrations induced by the skull. Sessions of 40 minutes at a 1% duty cycle with increased acoustic power, delivered 2 times per day for 5 days (10 sessions total). Receives: Device: Transcranial Ultrasonic Stimulation prototype |
| TUS - 40 min sessions, 5% duty cycle, increased acoustic power, 2 sessions/day (n=10) | Experimental | Low-intensity transcranial focused ultrasound stimulation of deep brain target, using a personalized acoustic lens to correct the aberrations induced by the skull. Sessions of 40 minutes at a 5% duty cycle with increased acoustic power, delivered 2 times per day for 5 days (10 sessions total). Receives: Device: Transcranial Ultrasonic Stimulation prototype |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent change in the Montgomery-Åsberg Depression Scale (MADRS) score from baseline to primary endpoint
MADRS is a ten item diagnostic questionnaire used to measure the severity of depressive symptoms in patients with mood disorders. Scale range - 0 to 60 with higher score indicative of greater depressive symptomology.
Measured: Pre-treatment and Day 5 from start of intervention
Secondary outcomes (7)
Incidence of serious adverse reactions according to the Common Terminology Criteria for Adverse Events (CTCAE) scale
CTCAE are a set of criteria for the standardized classification of adverse effects
Measured: Day 1 to Day 35 from start of intervention
Percent change in the Montgomery-Åsberg Depression Scale (MADRS)
MADRS is a ten item diagnostic questionnaire used to measure the severity of depressive symptoms in patients with mood disorders. Scale range - 0 to 60 with higher score indicative of greater depressive symptomology.
Measured: Pre-treatment and Day 1, Day 2, Day 3, Day 4, Day 5, Day 12 ± 2, Day 19 ± 2, Day 26 ± 2, Day 33 ± 2 from start of intervention
Percent change in the Hamilton Rating Scale for Depression (HDRS-17)
HDRS-17 is a 17 item questionnaire used to score the severity of depression. Scale range - 0 to 52 with higher score indicative of greater depressive symptomology.
Measured: Pre-treatment and Day 1, Day 2, Day 3, Day 4, Day 5, Day 12 ± 2, Day 19 ± 2, Day 26 ± 2, Day 33 ± 2 from start of intervention
Percent change in the Hamilton Rating Scale for Depression (HDRS-6)
HDRS-6 is a 6 item questionnaire used to score the severity of depression. Scale range - 0 to 22 with higher score indicative of greater depressive symptomology.
Measured: Pre-treatment and Day 1, Day 2, Day 3, Day 4, Day 5, Day 12 ± 2, Day 19 ± 2, Day 26 ± 2, Day 33 ± 2 from start of intervention
Percent change in the Inventory of Depressive Symptomatology (IDC-C)
IDS-C is a 30 item questionnaire used to score the severity of depression. Scale range - 0 to 90 with higher score indicative of greater depressive symptomology.
Measured: Pre-treatment and Day 1, Day 2, Day 3, Day 4, Day 5, Day 12 ± 2, Day 19 ± 2, Day 26 ± 2, Day 33 ± 2 from start of intervention
Percent change in the Quick Inventory of Depressive Symptomatology (QIDS-SR)
QIDS-SR is a 16 item self-administered questionnaire used to score the severity of depression. Scale range - 0 to 27 with higher score indicative of greater depressive symptomology.
Measured: Pre-treatment and Day 1, Day 2, Day 3, Day 4, Day 5, Day 12 ± 2, Day 19 ± 2, Day 26 ± 2, Day 33 ± 2 from start of intervention
Assess the changes in functional connectivity of sgACC after TUS
Comparison of functional connectivity of subgenual cingulate cortex through resting state imaging analysis before / after intervention
Measured: Pre-treatment and Day 7 from start of intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2023
- Study start9 May 2023
- Primary completionMay 2028 (estimated)
- Study completionJun 2028 (estimated)
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.
- More trials run by Centre Hospitalier St AnneThe 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
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier St Anne
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06085950
- Sponsor's protocol ID
- D21-P020
- Acronym
- StimulUS
- Status last verified
- Jun 2026
- First submitted
- 12 Sep 2023
- Last updated
- 22 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Attali D, Tiennot T, Manuel TJ, Daniel M, Houdouin A, Annic P, Dizeux A, Haroche A, Dadi G, Henensal A, Moyal M, Le Berre A, Paolillo C, Charron S, Debacker C, Lui M, Lekcir S, Mancusi R, Gallarda T, Sharshar T, Sylla K, Oppenheim C, Cachia A, Tanter M, Aubry JF, Plaze M. Deep transcranial ultrasound stimulation using personalized acoustic metamaterials improves treatment-resistant depression in humans. Brain Stimul. 2025 May-Jun;18(3):1004-1014. doi: 10.1016/j.brs.2025.04.018. Epub 2025 Apr 29.
PubMed 40311843
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transcranial Ultrasonic Stimulation in Treatment-resistant Depression: an Open-label Pilot Trial
- ClinicalTrials.gov ID
- NCT06085950
- Acronym / sponsor ID
- StimulUS / D21-P020
- Conditions
- Treatment Resistant Depression
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- Centre Hospitalier St AnneUniversity, hospital or other
- Study start
- 9 May 2023 (actual)
- Primary completion
- May 2028 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 17 Oct 2023 (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.
The primary objective of this study is to optimize the protocol for the TUS administration in patients with TRD while gaining an initial impression of treatment efficacy.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| TUS - 5 min sessions, 5% duty cycle, 5 sessions/day (n=5) | Experimental | Device: Transcranial Ultrasonic Stimulation prototypeLow-intensity transcranial focused ultrasound stimulation of deep brain target, using a personalized acoustic lens to correct the aberrations induced by the skull. Sessions of 5 minutes at a 5% duty cycle, delivered 5 times per day for 5 days (25 sessions total). |
| TUS - 40 min sessions, 5% duty cycle, 2 sessions/day (n=7) | Experimental | Device: Transcranial Ultrasonic Stimulation prototypeLow-intensity transcranial focused ultrasound stimulation of deep brain target, using a personalized acoustic lens to correct the aberrations induced by the skull. Sessions of 40 minutes at a 5% duty cycle, delivered 2 times per day for 5 days (10 sessions total). |
| TUS - 40 min sessions, 1% duty cycle, increased acoustic power, 2 sessions/day (n=10) | Experimental | Device: Transcranial Ultrasonic Stimulation prototypeLow-intensity transcranial focused ultrasound stimulation of deep brain target, using a personalized acoustic lens to correct the aberrations induced by the skull. Sessions of 40 minutes at a 1% duty cycle with increased acoustic power, delivered 2 times per day for 5 days (10 sessions total). |
| TUS - 40 min sessions, 5% duty cycle, increased acoustic power, 2 sessions/day (n=10) | Experimental | Device: Transcranial Ultrasonic Stimulation prototypeLow-intensity transcranial focused ultrasound stimulation of deep brain target, using a personalized acoustic lens to correct the aberrations induced by the skull. Sessions of 40 minutes at a 5% duty cycle with increased acoustic power, delivered 2 times per day for 5 days (10 sessions total). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age between 18 and 75 years,
- Diagnosis of major depressive episode (MDE) as part of major depressive disorder as defined by DSM-5 criteria
- Severe MDE (HDRS-17> 20)
- Drug resistance to at least two well-conducted antidepressant treatment lines
- With stable antidepressant treatment for at least 4 weeks before inclusion
Key exclusion criteria (8 listed)
- Psychiatric history other than a mood disorder
- Neurological history, including epilepsy and intracerebral calcifications
- History of substance use disorder other than tobacco
- Contraindication to brain MRI (pacemaker, neurostimulator, injury from metallic shine, …)
- Compulsory psychiatric care
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 Ultrasonic Stimulation prototypeTranscranial Ultrasonic Stimulation prototype delivers personalized low-intensity ultrasound stimulation | Device | TUS - 40 min sessions, 1% duty cycle, increased acoustic power, 2 sessions/day (n=10), TUS - 40 min sessions, 5% duty cycle, 2 sessions/day (n=7), TUS - 40 min sessions, 5% duty cycle, increased acoustic power, 2 sessions/day (n=10), TUS - 5 min sessions, 5% duty cycle, 5 sessions/day (n=5) |
Primary outcome
Percent change in the Montgomery-Åsberg Depression Scale (MADRS) score from baseline to primary endpoint
Time frame: Pre-treatment and Day 5 from start of intervention
MADRS is a ten item diagnostic questionnaire used to measure the severity of depressive symptoms in patients with mood disorders. Scale range - 0 to 60 with higher score indicative of greater depressive symptomology.
7 secondary outcomes
Incidence of serious adverse reactions according to the Common Terminology Criteria for Adverse Events (CTCAE) scale
Time frame: Day 1 to Day 35 from start of intervention
Percent change in the Montgomery-Åsberg Depression Scale (MADRS)
Time frame: Pre-treatment and Day 1, Day 2, Day 3, Day 4, Day 5, Day 12 ± 2, Day 19 ± 2, Day 26 ± 2, Day 33 ± 2 from start of intervention
Percent change in the Hamilton Rating Scale for Depression (HDRS-17)
Time frame: Pre-treatment and Day 1, Day 2, Day 3, Day 4, Day 5, Day 12 ± 2, Day 19 ± 2, Day 26 ± 2, Day 33 ± 2 from start of intervention
Percent change in the Hamilton Rating Scale for Depression (HDRS-6)
Time frame: Pre-treatment and Day 1, Day 2, Day 3, Day 4, Day 5, Day 12 ± 2, Day 19 ± 2, Day 26 ± 2, Day 33 ± 2 from start of intervention
Percent change in the Inventory of Depressive Symptomatology (IDC-C)
Time frame: Pre-treatment and Day 1, Day 2, Day 3, Day 4, Day 5, Day 12 ± 2, Day 19 ± 2, Day 26 ± 2, Day 33 ± 2 from start of intervention
Percent change in the Quick Inventory of Depressive Symptomatology (QIDS-SR)
Time frame: Pre-treatment and Day 1, Day 2, Day 3, Day 4, Day 5, Day 12 ± 2, Day 19 ± 2, Day 26 ± 2, Day 33 ± 2 from start of intervention
Assess the changes in functional connectivity of sgACC after TUS
Time frame: Pre-treatment and Day 7 from start of intervention
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 22 Jun 2026.
- Results publication: PubMed 40311843Attali D, Tiennot T, Manuel TJ, Daniel M, Houdouin A, Annic P, Dizeux A, Haroche A, Dadi G, Henensal A, Moyal M, Le Berre A, Paolillo C, Charron S, Debacker C, Lui M, Lekcir S, Mancusi R, Gallarda T, Sharshar T, Sylla K, Oppenheim C, Cachia A, Tanter M, Aubry JF, Plaze M. Deep transcranial ultrasound stimulation using personalized acoustic metamaterials improves treatment-resistant depression in humans. Brain Stimul. 2025 May-Jun;18(3):1004-1014. doi: 10.1016/j.brs.2025.04.018. Epub 2025 Apr 29.
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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.
David ATTALI contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial Ultrasonic Stimulation prototype in people with Treatment Resistant Depression, run by Centre Hospitalier St Anne at 1 site 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: looking for participants now, as of the sponsor's last update on 22 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. 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 Marion PLAZE (+33 1 45 65 87 20, m.plaze@ghu-paris.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent change in the Montgomery-Åsberg Depression Scale (MADRS) score from baseline to primary endpoint (time frame: Pre-treatment and Day 5 from start of intervention). 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 NCT06085950, 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 22 Jun 2026; AzTrials last refreshed its copy on 7 Nov 2026.