Focused Ultrasound for PTSD in Veterans

Phase 2

Not yet recruiting

• Conditions: Posttraumatic Stress Disorder

• Registration Number: NCT06820138
• Lead Sponsor: VA Office of Research and Development

Brief Summary

The goal of this study is to develop a new, non-invasive brain stimulation modality called low intensity focused ultrasound (FUS) as a psychiatric rehabilitation treatment for posttraumatic stress disorder (PTSD). FUS delivers energy comparable to that involved in diagnostic ultrasound but in a millimeter-sized envelope. Unlike currently available methods, the maximal FUS energy is delivered at a distance from a transducer on the scalp. Therefore, its promise is that it can deliver focal and reversible modulation to deeper brain regions involved in PTSD. The investigator team has previously conducted first-in-human research in FUS, and this study builds upon that work to conduct a phase II, dose-finding study. This study will pursue two Aims; the first is whether FUS to the amygdala can improve symptoms, and the second will evaluate whether FUS improves function by reduced disability, over a 1-month period. Short and longer-term effects of FUS will be measured and all FUS parameters are within FDA-defined safety thresholds for diagnostic ultrasound.

Detailed Description

PTSD is highly prevalent in Veterans and is associated with significant psychiatric and medical comorbidity and healthcare utilization. Most importantly, PTSD prevents Veterans from reintegrating into society and is associated with significant disability and psychosocial dysfunction. Despite its prevalence and devastating impact, even the most efficacious treatments have modest success in improving either symptoms or functioning in Veterans with PTSD. One reason for this limited efficacy is the inability for current treatments to directly target and engage deep brain regions which are directly involved in PTSD psychopathology. However, recent advances in the areas of neuroscience, psychiatry and technology allow, for the first time, development of new technologies that can non-invasively and reversibly modulate deep brain structures through the use of low intensity focused ultrasound (FUS). This application is targeting the amygdala, which is a core region involved in PTSD and many other psychiatric disorders.

To date, cleared uses of focused ultrasound are high-intensity sonication to irreversibly ablate tissue, therapeutically for movement disorders and cancer-related pain. Effects are highly focal (i.e., millimeter-scale), and occur without adjacent tissue damage. In contrast, FUS as it is proposed here uses acoustic energy at the same precision but within safety limits for diagnostic ultrasound. Although therapeutic use of FUS remains largely unexplored, several groups demonstrated that FUS can safely modulates neural activity in mice, rabbit, swine, and non-human primates. Even more recent data indicates FUS can safely modulate human cortical activity, including that of somatosensory and motor cortex as well as the thalamus in healthy individuals.

Our group has been leading the effort to evaluate the use of FUS, by delivering a single dose of FUS inside the bore of an MRI scanner to a group of depressed Veterans. However, FUS has not yet been developed for PTSD, and before rigorous clinical trials of FUS for PTSD can be initiated, several key questions remain and are the focus of this study.

Using a phase II-style proof of concept/dose-finding study, investigators will characterize the effects of sham-controlled FUS administrations. Veterans with chronic PTSD first receive an MRI scan to facilitate high-precision targeting using out-of-scanner stereotactic neuronavigation. After targeting, Veterans are randomized to receive sham FUS, or one, two, or three FUS administrations per week over a month, and then Veterans will be followed for up to three months to evaluate longer-term effects. Neuroimaging MRI will be obtained prior to and following completion of FUS to explore neural effects. Thus, this study will evaluate the short-term durability of any effects on symptoms and function, and the design will provide important insight into the potential use for repeated administrations over time. The significance of this project lies in the potential to develop non-invasive deep brain stimulation for PTSD, with lessons learned that will be applicable for broader implementation; this goal can be realized through this careful and programmatic phase II study.

Study Timeline

• Study First Submitted: 2025-01-27
• Status Verified: 2025-02
• Study First Submitted QC: 2025-02-05
• Study First Posted: 2025-02-11
• Last Update Submitted: 2025-02-13
• Last Update Posted: 2025-02-18
• Study Start: 2026-02-02
• Primary Completion: 2029-06-29
• Study Completion: 2029-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

-Veterans ages 22-70 (inclusive) who meet DSM-5 criteria for chronic PTSD using the Clinician Administered PTSD Scale for DSM-5 (CAPS-5) and currently symptomatic. If applicable, Veterans will be required to be on stable psychiatric treatment(s) prior to baseline assessments

Exclusion Criteria

• contraindications to focused ultrasound and/or neuroimaging:

  • i) history of seizure disorder or serious neurologic illness including dementia or serious cognitive impairment,
  • ii) structural or neurologic abnormalities present or in close proximity to sonication site ,
  • iii) prior brain surgery,
  • iv) pacemaker or implanted central nervous system device,
  • v) greater than mild traumatic brain injury, or any head injury within sixty days of ultrasound,
  • vi) greater than moderate alcohol or substance use disorders or active use or withdrawal from alcohol or substances,
  • vii) metal in the head,
  • viii) physical impediment likely to interfere with assessments, or
  • ix) unable to follow protocols.
  • x) Veterans with significant white matter findings or those with findings in the beam of the ultrasound may also be excluded at discretion of study staff.

• Veterans with acute suicidality are also excluded.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
PTSD Checklist for DSM5	Up to 3 months	The PTSD Checklist for Diagnostic and Statistical Manual-5 (PCL-5) is a gold standard self reported scale of PTSD symptoms. Scores range from 0-80, where higher scores indicate greater symptom severity. The Week 5 visit value is the primary outcome measure of the study.

Secondary Outcome Measures

Name	Time	Method
Sheehan Disability Scale	Up to 3 months	The Sheehan Disability Scale (SDS) is a self report tool used to assess functional impairment in work, social and family life. Scores range from 0-30, where higher scores indicate greater impairment.
Social and Occupational Function Scale	Up to 3 months	The Social and Occupational Function Scale (SOFAS) assesses social and occupational function, and is scored from 0-100, where higher scores indicate superior (better) social and occupational function.
Inventory of Depressive Symptoms Self Report	Up to 3 months	The Inventory of Depressive Symptoms, Self-Report (IDSSR) is a rating scale that measures self-reported depressive symptoms. Scores range from 0-84, where higher scores indicate more severe depressive symptom severity.
Clinician Administered PTSD Scale	Up to 3 months	The Clinician Administered Posttraumatic Stress Disorder Scale for Diagnostic and Statistical Manual-5 (CAPS-5) is structured clinical interview for posttraumatic stress disorder symptoms. Scores range from 0-80, where higher symptoms indicate more severe symptom severity.
Clinician Global Impression	Up to 3 months	The Clinician Global Impression scale assesses a clinician's general impression of severity. Scores typically range from 1 (not at all ill) to 7 (very ill); Improvement scores range from 1 (very much improved) to 7 (very much worse).

Trial Locations

Locations (1)

Providence VA Medical Center, Providence, RI; 🇺🇸 Providence, Rhode Island, United States