Focused Ultrasound for the Complex Patient

NCT ID: NCT06453109

Last Updated: 2024-11-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-29
• Study Completion Date: 2025-09-30

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.

Conditions

Opioid Use Disorder; Chronic Back Pain; Anxiety

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

LIFU/Sham

double-blind, sham-controlled, crossover study in N=25 individuals with opiate use disorder, anxiety, and chronic back pain

Group Type: OTHER

low intensity focused ultrasound (LIFU)

Intervention Type: DEVICE

Low-intensity focused ultrasound (LIFU) provides an energy source with millimeter resolution that can be focused anywhere in the brain safely and effectively for non-invasive and transient neuromodulation. LIFU is an important advance and of great significance for brain-mapping efforts, diagnostics, and therapies in neuroscience and particularly promising for addiction therapy as it provides unprecedented non-surgical access to the brain regardless of depth.

Much lower intensities of focused ultrasound (LIFU) are used so that tissue damage does not occur, but neural activity can be modulated. LIFU utilizes acoustic energy at much lower levels to affect tissue by mechanical effects.

Sham/LIFU

double-blind, sham-controlled, crossover study in N=25 individuals with opiate use disorder, anxiety, and chronic back pain

Group Type: OTHER

low intensity focused ultrasound (LIFU)

Intervention Type: DEVICE

Low-intensity focused ultrasound (LIFU) provides an energy source with millimeter resolution that can be focused anywhere in the brain safely and effectively for non-invasive and transient neuromodulation. LIFU is an important advance and of great significance for brain-mapping efforts, diagnostics, and therapies in neuroscience and particularly promising for addiction therapy as it provides unprecedented non-surgical access to the brain regardless of depth.

Much lower intensities of focused ultrasound (LIFU) are used so that tissue damage does not occur, but neural activity can be modulated. LIFU utilizes acoustic energy at much lower levels to affect tissue by mechanical effects.

Interventions

low intensity focused ultrasound (LIFU)

Low-intensity focused ultrasound (LIFU) provides an energy source with millimeter resolution that can be focused anywhere in the brain safely and effectively for non-invasive and transient neuromodulation. LIFU is an important advance and of great significance for brain-mapping efforts, diagnostics, and therapies in neuroscience and particularly promising for addiction therapy as it provides unprecedented non-surgical access to the brain regardless of depth.

Much lower intensities of focused ultrasound (LIFU) are used so that tissue damage does not occur, but neural activity can be modulated. LIFU utilizes acoustic energy at much lower levels to affect tissue by mechanical effects.

Intervention Type: DEVICE

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

Washington D.C. Veterans Affairs Medical Center

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mary R Lee, MD

Role: PRINCIPAL_INVESTIGATOR

Washington D.C. Veterans Affairs Medical Center

Locations

Washington DC Veterans Affairs Medical Center

Washington D.C., District of Columbia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Mary R Lee, MD

Role: CONTACT

mary.lee3@va.gov

202-745-8000 ext. 58128

Krystian Burum, MS

Role: CONTACT

krystian.burum@va.gov

Facility Contacts

Mary R Lee, MD

Role: primary

mary.lee3@va.gov

(202) 745-8000 ext. 58128

Mary R Lee, MD

Role: backup

Other Identifiers

UG3DA059407

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1777666

Identifier Type: -

Identifier Source: org_study_id