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.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

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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.

Marion PLAZE contact

+33 1 45 65 87 20

m.plaze@ghu-paris.fr

David ATTALI contact

d.attali@ghu-paris.fr

France1 site, 1 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
Recruiting

Other trials in France

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 groups in NCT06085950
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.

9 May 2023Jun 2028

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)

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

Interested in taking part?

Marion PLAZE

+33 1 45 65 87 20

m.plaze@ghu-paris.fr

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See sites and contacts

RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
RecruitingPhase 2
ACP-211 Monotherapy for Major Depressive Disorder With Inadequate Antidepressant Response
Major Depressive Disorder (MDD), Depressive Disorder, Treatment-Resistant
Active, not recruiting
CET- REM (Correlating ECT Response to EEG Markers)
ECT, Treatment Resistant Depression
Active, not recruiting
rTMS to Target Neural Connectivity and Rumination in Treatment-Resistant Depression
Depression, Treatment Resistant
Recruiting
A Prospective, Multi-center, Randomized Controlled Blinded Trial Demonstrating the Safety and Effectiveness of VNS Therapy® System as Adjunctive Therapy Versus a No Stimulation Control in Subjects With Treatment-Resistant Depression
Treatment Resistant Depression

All Treatment Resistant Depression trials

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.

Related trials for Treatment Resistant Depression

RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
RecruitingPhase 2
ACP-211 Monotherapy for Major Depressive Disorder With Inadequate Antidepressant Response
Major Depressive Disorder (MDD), Depressive Disorder, Treatment-Resistant
Active, not recruiting
CET- REM (Correlating ECT Response to EEG Markers)
ECT, Treatment Resistant Depression
Active, not recruiting
rTMS to Target Neural Connectivity and Rumination in Treatment-Resistant Depression
Depression, Treatment Resistant
Recruiting
A Prospective, Multi-center, Randomized Controlled Blinded Trial Demonstrating the Safety and Effectiveness of VNS Therapy® System as Adjunctive Therapy Versus a No Stimulation Control in Subjects With Treatment-Resistant Depression
Treatment Resistant Depression

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.

Marion PLAZE contact

+33 1 45 65 87 20

m.plaze@ghu-paris.fr

David ATTALI contact

d.attali@ghu-paris.fr

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.