Transcranial Pulse Stimulation for Depression

Study Overview
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Brief Summary
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Transcranial pulse stimulation (TPS) is a newly developed brain stimulation therapy from Austria & Germany with highly promising applicability in neuropsychiatric disorders. Major depressive disorder (MDD) is the world's leading cause of disability. Novel treatment approaches are urgently needed given that a significant fraction of patients does not sufficiently respond to standard antidepressant treatments. Our open-label pilot study using TPS in MDD indicates preliminary efficacy. However, experimental control is necessary to infer reliable scientific evidence for the efficacy of TPS. Here, we propose a randomized, double-blind, sham-controlled clinical trial to probe the utility of TPS as a modern antidepressant treatment.

Official Title
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A Randomized, Double-blind, Sham-controlled Clinical Trial of Transcranial Pulse Stimulation for the Treatment of Major Depression

Conditions
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Major Depression

Intervention / Treatment
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* Device: Transcranial pulse stimulation


Participation Criteria
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Eligibility Criteria
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MDD group Inclusion Criteria: Age 18 to 60; A clinical diagnosis of a MDD and a HAMD17 score ≥14; Treatment naivety or stable (≥4 weeks) psychopharmacological medication. Exclusion Criteria: Severe internal diseases including blood clotting disorders; Neurological disorders including bleeding prone micro-pathologies or a history of severe head injuries; Current psychiatric comorbidities, including addiction; Pregnancy; Common NIBS exclusion criteria, such as a history of brain surgery, cardiac pacemaker, deep brain stimulation and intracranial metallic particles.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Basic Science
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Real TPS treatment group<br>Participants with MDD will receive TPS treatment lasting for 4 weeks (3 sessions per week). A follow-up assessment will be scheduled 3 months after the last REAL treatment day. MRI measurements will be conducted before the start of treatment (within one week before treatment start), as well as after the last treatment day (within one week post-treatment) | Device: Transcranial pulse stimulation<br>* TPS will be performed in three treatment sessions per week, applying 1000 pulses per session (single ultrashort (3 μs) ultrasound pulses, 0.2-0.25 mJ mm-2,  5 Hz pulse frequency,<br>|
| Sham Comparator: Sham TPS treatment<br>Participants will receive sham TPS treatment lasting for 4 weeks (3 sessions per week, as done previously. After treatment end and completed assessments, the study will be unblinded and participants in the sham treatment arm will receive real TPS. A follow-up assessment will be scheduled 3 months after the last REAL treatment day. MRI measurements will be conducted before the start of treatment (within one week before treatment start), as well as after the last treatment day (within one week post-treatment), | Device: Transcranial pulse stimulation<br>* TPS will be performed in three treatment sessions per week, applying 1000 pulses per session (single ultrashort (3 μs) ultrasound pulses, 0.2-0.25 mJ mm-2,  5 Hz pulse frequency,<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in depressive symptoms after the treatment | Primary clinical outcome measure will be a change in Montgomery-Åsberg Depression Rating Scale (MADRS) score (range from 0-60) after six weeks of treatment. Higher scores indicative of greater depressive symptomology in MADRS | four weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in depressive symptoms in the follow-up stage | Change of Montgomery-Åsberg Depression Rating Scale (MADRS) score (range from 0-60) at 3-months follow-up. Higher scores indicative of greater depressive symptomology in MADRS. | at 3 months follow-up | 
| Change in depressive symptoms | Change of Hamilton Depression Rating Scale (HAMD17, range from 0-54) scores after four weeks of treatment and at 3-months follow-up. Higher scores indicative of greater depressive symptomology in HAMD-17 | four weeks of treatment and at 3 months follow-up | 
| Change in depressive symptoms | Change of Patient Health Questionnaire (PHQ-9, range from 0-27) scores after four weeks of treatment and at 3-months follow-up. Higher scores indicative of greater depressive symptomology in PHQ-9 | four weeks of treatment and at 3 months follow-up. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transcranial pulse stimulation, Brain stimulation, Major depression