Clinical trial NCT06820138: Focused Ultrasound for PTSD in Veterans
Official title: Low Intensity Focused Ultrasound for Posttraumatic Stress Disorder
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Posttraumatic Stress Disorder
Keywords: Low intensity focused ultrasound
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2025-02-11
Enrollment: 60
Sex: ALL
Minimum age (years): 22
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind delivery of low intensity focused ultrasound (i.e., active low intensity focused ultrasound versus a sham (placebo) administration of low intensity focused ultrasound). Sessions are approximately three times a week for four weeks.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: PTSD Checklist for DSM5
timeFrame: Up to 3 months
Secondary outcomes:
measure: Sheehan Disability Scale
timeFrame: Up to 3 months
measure: Social and Occupational Function Scale
timeFrame: Up to 3 months
measure: Inventory of Depressive Symptoms Self Report
timeFrame: Up to 3 months
measure: Clinician Administered PTSD Scale
timeFrame: Up to 3 months
measure: Clinician Global Impression
timeFrame: Up to 3 months
Other outcomes:
measure: Visual Analog Scale
timeFrame: Three times per week for up to five weeks
measure: Arterial Spin Labeling/fMRI
timeFrame: Five weeks
Locations:
city: Providence
country: United States
facility: Providence VA Medical Center, Providence, RI
state: Rhode Island
Study officials:
affiliation: Providence VA Medical Center, Providence, RI
name: Noah S. Philip, MD
role: PRINCIPAL_INVESTIGATOR
References: