Clinical trial NCT06453109: Focused Ultrasound for the Complex Patient
Official title: Towards Treatment of the Complex Patient: Investigations of Low-intensity Focused Ultrasound
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Opioid Use Disorder
Chronic Back Pain
Anxiety
Keywords: anxiety disorders
oud
opiate use disorder
opioid
back pain
chronic back pain
opioid use
opioid abuse
opioid disorder
low intensity focused ultrasound
transcranial ultrasound
Lead sponsor: Washington D.C. Veterans Affairs Medical Center
Sponsor class: FED
Collaborators: name: National Institutes of Health (NIH)
name: National Institute on Drug Abuse (NIDA)
First posted: 2024-06-11
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: within subject, randomized, double-blind, sham-controlled trial
Primary purpose: BASIC_SCIENCE

Brief summary: The goal of this clinical trial is to to inhibit the anterior insula (AI) with low intensity focused ultrasound (LIFU) to determine the causal role for the AI in pain processing, anxiety, and opiate cue-induced craving. The main question\[s\] it aims to answer are:

* the safety and tolerability of LIFU delivered bilaterally to AI compared to sham stimulation in individuals with opiate use disorder (OUD), anxiety, and chronic back pain
* the effects of LIFU vs sham on measures of pain processing, anxiety symptoms, and opiate cue-induced craving

Participants will undergo anatomical MRI, neurological assessment, clinical assessment and patient query to assess the safety and tolerability of LIFU vs sham.

Detailed description: Opioid use disorder with co-morbid chronic pain and anxiety is a clinical triad associated with the highest risk of opiate overdose deaths. Co-occurrence of these three disorders amplifies symptoms of each and results in poorer treatment outcomes. There are shared neurobiological substrates for these disorders such as reward processing and stress response. The anterior insula (AI) is a brain region involved in these processes as well as in clinical disorder of pain, addiction, and anxiety. The AI is upregulated in pain, addiction and anxiety disorders and is therefore a potential therapeutic target for neuromodulation. Low-intensity focused ultrasound (LIFU) is a noninvasive method to inhibit cortical and deep brain regions. LIFU can reach deep brain regions such as the AI with spatial specificity, unlike traditional noninvasive neuromodulation methods which lack spatial specificity and depth penetration. LIFU can selectively target the insula and its subregions and provides a potentially transformative method to reduce symptoms of pain, opiate craving, and anxiety in a complex patient population such as co-morbid chronic pain, anxiety, and opioid use disorder. In this study, the investigators will administer one session of inhibitory LIFU to the AI in individuals with opiate use disorder, chronic back pain, and anxiety disorders (generalized anxiety disorder, post-traumatic stress disorder, or social anxiety disorder)\]. The aim of this phase of the study is to establish that LIFU vs sham LIFU to AI is safe and well tolerated as measured by adverse events, clinical evaluation and repeated structural brain magnetic resonance imaging scans. The investigators will also gather preliminary data on the effect of LIFU to AI on opiate cue-induced craving and laboratory measures of central sensitization(CS) which occurs with pain chronicity such as temporal summation of pain and conditioned pain modulation. There is a need for improved treatments for complex patients such as co-morbid chronic back pain, anxiety, and opioid use disorder beyond combining treatments for each disorder. LIFU provides an ability to transiently and selectively inhibit AI to determine its causal role in co-morbid chronic back pain, anxiety, and opioid use disorder symptoms which then may lead to improved treatments for this clinical triad which is associated with poor treatment outcomes.

Eligibility criteria: Inclusion Criteria:

1. Males and females aged 18-75 years
2. Current diagnosis of Chronic Back Pain as defined by pain duration of at least three months, with back pain being an ongoing problem for at least half the days of the last six months.
3. Have evidence of central sensitization (CS) as measured by the Widespread Pain/Symptom Severity Index (WPSSI) with a score of Widespread Pain Index (WPI) ≥ 7 and Symptom Severity (SS) ≥ 5 or WPI = 3-6 and SS ≥ 9.
4. Participants must rate pain intensity at 4/10 or greater on the Brief Pain Inventory-Short Form (BPI-SF)
5. Meet the DSM-5 criteria for current opiate use disorder as diagnosed by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.
6. Be in treatment for OUD including buprenorphine or methadone.
7. Meet the DSM-5 criteria for a current anxiety disorder: generalized anxiety disorder, post-traumatic stress disorder or social anxiety disorder as diagnosed by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition(DSM-5).

Exclusion Criteria:

1. Evidence of neuropathic pain
2. Current DSM-5 substance use disorder other than OUD, tobacco use disorder
3. Current DSM-5 diagnosis of schizophrenia or schizo-affective disorder
4. Pregnant or breastfeeding
5. Daily use of benzodiazepines or opiates (other than buprenorphine or methadone)
6. History of seizures, neurologic disorders, including cerebrovascular disease, history of stroke, brain surgery, brain tumor, multiple sclerosis, or neurodegenerative diseases. They will not have history of metastasizing cancers, inflammatory disorder: rheumatoid arthritis, polymyalgia rheumatica, scleroderma, lupus or polymyositis, unintended weight loss of 20 pounds or more in the last year, or cauda equina syndrome.
7. Ferromagnetic implants or other contraindications for MRI
8. Unstable medical conditions such as congestive heart failure, unstable angina, poorly controlled arrhythmia active systemic infection end stage renal disease.

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: immediately prior to 1 session low-intensity focused ultrasound (LIFU) and within 1 hour post LIFU; immediately prior to 1 session sham and with in 1 hour post sham
Secondary outcomes:
measure: Heart rate variability
timeFrame: immediately prior to 1 session low-intensity focused ultrasound (LIFU) and within 1 hour post LIFU; immediately prior to 1 session sham and with in 1 hour post sham
measure: Pain threshold
timeFrame: immediately prior to 1 session low-intensity focused ultrasound (LIFU) and within 1 hour post LIFU; immediately prior to 1 session sham and with in 1 hour post sham
Other outcomes:
Locations:
city: Washington
country: United States
facility: Washington DC Veterans Affairs Medical Center
state: District of Columbia
Study officials:
affiliation: Washington D.C. Veterans Affairs Medical Center
name: Mary R Lee, MD
role: PRINCIPAL_INVESTIGATOR
References: