Clinical trial NCT06273904: Modulating Escape Using Focused Ultrasound
Official title: Modulating Escape in the Anxiety Disorder Spectrum: Targeting the Direct Neural Mediator Using Transcranial Focused Ultrasound
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Anxiety Disorders
Lead sponsor: Medical University of South Carolina
Sponsor class: OTHER
First posted: 2024-02-23
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: This is a study to find out if a cutting-edge technology called transcranial focused ultrasound (tFUS) can be used to treat how people with anxiety or related concerns cope with emotional situations. tFUS is a brain stimulation technology that causes temporary changes in the activity of deep brain areas without a need for any surgery or other permanent or invasive procedures.

This study is recruiting participants who recently started treatment for anxiety or a related concern to come in for 3 visits at the Medical University of South Carolina. At the first visit, participants will do interviews and surveys asking about anxiety and related concerns, and they do tasks where they respond to emotional pictures while brain activity is measured using magnetic resonance imaging (MRI). At the next two visits, participants again do a task where they see and react to emotional images, and this time the task is done once before and again once after receiving tFUS that either actively causes temporary changes (lasting for about an hour) in a targeted brain area or is not active (no changes elicited). At each tFUS visit, responses are measured with sensors worn on the hand, arms, face, and head (these visits do not involve MRI).

Each visit in this study is expected to last between 2 - 3 hours. This study is not a treatment study, but it could help improve treatment in the future. Participants in this study are paid for their time.

Detailed description: Escape and avoidance are core targets of anxiety and related disorder treatment, but such behaviors also often persist even after reduction of reported symptoms or they keep an individual from engaging in treatment at all. Novel methods to directly target motive drivers of escape/ avoidance coping early in treatment are needed to improve retention and outcome especially for the 20% of individuals who do not benefit from and 40% who do not complete treatment. Basic science identifies multiple neural mediators of real-world escape and avoidance, and it suggests these mediators may not be directly or adequately targeted by current treatment techniques. Moreover, the direct neural mediators may be primarily subcortical and thus not be accessible to therapeutic technologies like transcranial magnetic stimulation that can only stimulate cortical areas. A novel technology called transcranial focused ultrasound (tFUS), meanwhile, has demonstrated ability to non-invasively and stimulate even the deepest areas of the brain in humans, and thus may have utility in directly modulating the subcortical drivers of exaggerated escape/ avoidance coping. Given this exciting possibility, the primary goal of this research is to determine if tFUS to subcortical neural mediators can be used to cause measurable changes in the downstream escape/ avoidance dispositions. Results will then inform the potential use of noninvasive tFUS stimulation as a precursor to evidence-based therapy to reduce risk of dropout and enhance outcomes.

Eligibility criteria: Inclusion Criteria:

* 18-65 y.o.
* Meets criteria for an anxiety disorder (Generalized Anxiety Disorder, Panic Disorder, Social Anxiety Disorder, Specific Phobia), posttraumatic stress disorder, obsessive-compulsive disorder, or current adjustment disorder with anxiety
* Is currently seeking mental health treatment
* Is able to read consent document and provide informed consent.
* English is a first or primary fluent language.

Exclusion Criteria:

* Current alcohol or substance use disorder of more than mild severity (as defined by the Diagnostic and Statistical Manual (DSM)-5 and determined using standardized self-report instruments)
* Lifetime diagnosis of psychotic disorder or bipolar mania
* Presence of neurological disorder that contraindicates brain stimulation or neurophysiological recording: Seizure disorder
* Lifetime history of traumatic brain injury with loss of consciousness
* Neurodegenerative disorder (e.g., Alzheimer's Disease, Parkinson's Disease, Frontotemporal Dementia)
* Presence of other medical disorder that would make it too uncomfortable to sit or lie still for long recording periods
* Presence of standard contraindications for magnetic resonance imaging
* Metal in the body
* Currently pregnant
* Claustrophobia
* Significant sensitivity to noise
* Medical conditions or treatments that lower seizure threshold
* History of severe brain injury
* History of seizures/ epilepsy
* Currently taking anticholinergic mediation, neuroleptic medication, or sedative/ hypnotic medication

Note: selective serotonin re-uptake inhibitors (SSRIs), cholinesterase inhibitors or N-methyl-D-aspartate (NMDA) receptor antagonists are allowed if patient has been on a stable regimen of four weeks prior to enrollment

* Currently taking chronic opiate medications or substances
* Currently taking naltrexone

Primary outcomes:
measure: Change in Fear-Potentiated Startle Reflex
timeFrame: Immediately Pre-Stimulation and Immediately Post-Stimulation (Approx. 10 minutes between assessments)
Secondary outcomes:
measure: Change in speed to initiate avoidance behavior
timeFrame: Immediately Pre-Stimulation and Immediately Post-Stimulation (Approx. 10 minutes between assessments)
measure: Change in Electroencephalography (EEG)-Assessed Contingent Negative Variation During Escape/ Avoidance Preparation
timeFrame: Immediately Pre-Stimulation and Immediately Post-Stimulation (Approx. 10 minutes between assessments)
measure: Change in Electroencephalography (EEG)-Assessed N200 During Implicit Approach/ Avoid Bias Assessment
timeFrame: Immediately Pre-Stimulation and Immediately Post-Stimulation (Approx. 10 minutes between assessments)
measure: Change in Electroencephalography (EEG)-Assessed Theta-Band Power During Behavioral Tasks
timeFrame: Immediately Pre-Stimulation and Immediately Post-Stimulation (Approx. 10 minutes between assessments)
measure: Change in High-Frequency Heart Rate Variability/ Respiratory Sinus Arrhythmia
timeFrame: Immediately Pre-Stimulation and Immediately Post-Stimulation (Approx. 10 minutes between assessments)
measure: Change in Task-Based Heart Rate (Beats per Minute) Changes
timeFrame: Immediately Pre-Stimulation and Immediately Post-Stimulation (Approx. 10 minutes between assessments)
measure: Change in Task-Based Galvanic Skin Conductance
timeFrame: Immediately Pre-Stimulation and Immediately Post-Stimulation (Approx. 10 minutes between assessments)
measure: Change in State Anxiety During Session
timeFrame: Immediately Pre-Stimulation and Immediately Post-Stimulation (Approx. 10 minutes between assessments)
Other outcomes:
measure: Task-Related Regional Brain Activation
timeFrame: During Session (Approx. 45 minutes)
Locations:
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
Study officials:
affiliation: Medical University of South Carolina
name: Christopher Sege, PhD
role: PRINCIPAL_INVESTIGATOR
References: