Transcranial Ultrasonic Stimulation in Treatment-resistant Depression : an Open-label Pilot Trial

NCT06085950 | Recruiting DMC

• 1 other identifier: D21-P020
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Treatment Resistant Depression

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  Day 1 to Day 35 from start of intervention

• Percent change in the Montgomery-Åsberg Depression Scale (MADRS)

  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)

  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)

  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)

  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

Study Arms (4)

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).

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).

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).

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).

Device: Transcranial Ultrasonic Stimulation prototype

Interventions

Transcranial Ultrasonic Stimulation prototype DEVICE

Transcranial Ultrasonic Stimulation prototype delivers personalized low-intensity ultrasound stimulation

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)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Benefiting from a social security scheme
• Having given their consent to participate

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre Hospitalier St Anne: lead

Study Sites (1)

GHU Sainte-Anne

Paris, 75014, France

RECRUITING

Related Publications (1)

• 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.

  PMID: 40311843 RESULT

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Central Study Contacts

Marion PLAZE

CONTACT

+33 1 45 65 87 20; m.plaze@ghu-paris.fr

David ATTALI

CONTACT

d.attali@ghu-paris.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2023
• First Posted: October 17, 2023
• Study Start: May 9, 2023
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: June 22, 2026

Record last verified: 2026-06

Locations

FR (1)