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

Study Overview
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Brief Summary
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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.

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

Conditions
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Treatment Resistant Depression

Intervention / Treatment
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* Device: Transcranial Ultrasonic Stimulation prototype


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transcranial Ultrasonic Stimulation with Personalized Acoustic Lens<br>Low-intensity transcranial focused ultrasound stimulation of deep brain target, using a personalized acoustic lens to correct the aberrations induced by the skull | Device: Transcranial Ultrasonic Stimulation prototype<br>* Transcranial Ultrasonic Stimulation prototype delivers personalized low-intensity ultrasound stimulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | 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. | 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. | 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. | 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. | 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 | Pre-treatment and Day 7 from start of intervention |