Actively Recruiting
Parsing Mechanistic Relationships Between Circuits and Negative Valence System Behaviors in Treatment-Resistant Depression With Ultrasound Neuromodulation
Led by Laureate Institute for Brain Research, Inc. · Updated on 2026-03-02
140
Participants Needed
1
Research Sites
13 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are studying treatment-resistant Major Depressive Disorder (MDD), a condition affecting about one third of people with depression who do not respond well to typical treatments and suffer from severe symptoms like anhedonia and rumination. This study aims to understand how brain circuits related to Negative Valence Systems contribute to these symptoms by using low-intensity focused ultrasound (LIFU) to modulate deep brain connections non-invasively. The goal is to better define brain targets that could lead to improved neuromodulation therapies for this population in need of new treatments. The study will involve 120 participants with treatment-resistant depression who will receive either LIFU targeting deep white matter tracts connecting the thalamus to the orbitofrontal cortex (OFC) or anterior cingulate cortex (ACC), or a sham (placebo) stimulation. Each ultrasound treatment consists of an 80-second train of 20-millisecond bursts delivered non-invasively. The targets are personalized using advanced brain imaging to match each participant's anatomy. The trial uses a randomized, triple-blind design with two experimental arms and one sham comparator. Participants will undergo brain scans including resting-state functional MRI before and up to 30 minutes after sonication or sham intervention. Behavioral assessments will measure reward processing and rumination to explore changes related to the ultrasound treatment. The main outcomes include changes in brain connectivity and behavior after sonication. The study includes monitoring of symptoms, safety, and adherence, with participation lasting through the immediate post-treatment assessment period. This research aims to clarify brain-behavior links and inform future precision neuromodulation strategies in depression.
CONDITIONS
Brief Title
Ultrasound Neuromodulation of Circuits and Negative Valence Systems in Treatment-Resistant Depression
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Persons aged 18 to 65 years
- Confirmed diagnosis of Major Depressive Disorder by DSM-5-TR and psychiatrist
- Evidence of treatment resistance with ongoing symptoms despite two or more antidepressant trials, psychotherapy, augmentation agents, or ECT considerations
- Moderate or greater symptom severity indicated by MADRS score of 20 or higher
- Stable treatments including medication and psychotherapy for at least six weeks
- Fluent in English and able to provide written consent
- Agree to allow random observations of brain pathology during imaging
You will not qualify if you...
- History of neurocognitive disorder of neurodegenerative origin
- Cognitive function score (PROMIS) of 40 or below at baseline
- Structural brain pathology such as Parkinson's disease, multiple sclerosis, or brain tumors
- Uncontrolled diabetes or hypertension at baseline
- Pregnancy or lactation
- Positive test for alcohol or drugs of abuse or substance use disorder exceeding mild severity in past 6 months
- Active suicidal thoughts or recent suicide attempt
- MRI contraindications or inability to complete MRI scans
- Moderate to severe traumatic brain injury history
- Current psychotic, eating, learning disability, or personality disorder interfering with study adherence
- Moderate or severe substance or alcohol use disorder
- Use of benzodiazepines or anticonvulsants within 7 days before screening
- Conditions limiting ability to consent, follow protocol, or complete study
- No reliable method of communication (internet or phone access)
- Use of medications outside accepted range
- Unwilling or unable to complete major study procedures
- Non-correctable vision or hearing problems
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Single sessions lasting up to 30 minutes post-sonication
Participants receive low-intensity focused ultrasound (LIFU) or sham stimulation targeting specific brain circuits to study their effects on depression-related behaviors.
Multiple visits for sonication and assessments
Trial Site Locations
Total: 1 location
1
Laureate Institute for Brain Research
Tulsa, Oklahoma, United States, 74136
Actively Recruiting
Research Team
S
Salvador M Guinjoan, MD, PhD
D
Danielle E Clark, MA
How is the study designed?
Study Type
INTERVENTIONAL
Masking
TRIPLE
Allocation
RANDOMIZED
Model
CROSSOVER
Primary Purpose
BASIC_SCIENCE
Number of Arms
3
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