Low Intensity Focused Ultrasound for Chronic Pain: High Resolution Targeting of The Human Insula

NCT ID: NCT06906211

Last Updated: 2025-04-02

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-15
• Study Completion Date: 2028-01-26

Brief Summary

In this study, the research team will use low-intensity focused ultrasound (LIFU) to temporarily change brain activity in a brain region that is known to be involved in chronic pain. Through this, the research team hopes to learn about how the brain area works in response to pain. There are main questions this study aims to answer:

• The effect of LIFU to inhibit the posterior region of the insula (PI) compared to sham stimulation in individuals with chronic back pain (CBP) and widespread pain symptoms.
• The effect of LIFU to PI compared to sham stimulation to reduce pain intensity and magnitude of the Neurologic Pain Signature (NPS) in response to evoked thermal pain.
• The effect of LIFU to PI compared to sham stimulation to reduce pain intensity and magnitude of Tonic Pain Signature in response to tonic pain.

Detailed Description

Chronic pain is a major public health problem. An estimated 100 million Americans have experienced chronic pain producing significant economic and social burden. The estimated annual cost of chronic pain is as high as $635 billion. Pharmacological treatments frequently require the use of opioids resulting in a major epidemic of abuse in the United States. New, non-addicting treatments for pain are critically needed. Neuromodulation with low-intensity focused ultrasound (LIFU) could represent a non-pharmacological treatment for chronic pain. The millimeter spatial specificity of LIFU makes it a powerful alternative to both invasive neurosurgical procedures and other noninvasive brain stimulation techniques. One promising target to treat chronic pain is the insular cortex. The insula as a key brain area involved in both sensory and affective components of chronic pain, including central sensitization processes which occur with pain chronicity. The insula is inaccessible using conventional noninvasive neuromodulatory techniques like transcranial magnetic stimulation. In contrast, LIFU can be focused deeply and provides the spatial resolution to resolve individual sub-regions of the insula. This is relevant to pain as the posterior subregion of the insula (PI) receives nociceptive input from spinothalamic tracts, relays it to the anterior insula which integrates expectation, awareness, and emotion to form the overall experience of pain. Therefore, using LIFU can address a gap in knowledge regarding the causal role of insular subregions in modulating pain response and CS processes. The preliminary data indicate that LIFU to PI reduces laboratory measures of central sensitization and evoked pain in healthy controls but there was no such effect of LIFU to anterior insula. Building on these results, the overall objective of this proposal is to examine the effect of LIFU to PI on the central sensitization processes that are a key feature of chronic pain syndromes and on neural response to evoked and tonic pain/pain intensity. The investigators will employ well validated laboratory measures of central sensitization and multivariate measures of neural response to evoked (Neurologic Pain Signature, NPS) and tonic (Tonic Pain Signature) pain. The chronic pain condition that the investigators will focus on in this study will be chronic back pain (CBP) with widespread pain widespread pain as the back is the most common site of chronic pain, is significantly more likely to be severe in the veteran population, and it commonly occurs with features of central sensitization. Eligible participants will have CBP with symptoms of widespread pain.

Conditions

Chronic Back Pain; Chronic Pain (Back / Neck)

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=66 individuals with 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=66 individuals with 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

• Veterans aged 21 to 75 with Chronic Back Pain (CBP).
• CBP duration daily for last 3 months or half of days for last 6 months
• Endorse pain rating of 4/10 BPI-SF
• Evidence of widespread pain symptoms as determined by report of CBP and pain in a contralateral limb (pain in the upper, lower, left or right side of the body) in fewer than 11 sites. Upper body sites include hand, wrist, elbow or shoulder. Lower sites include hip, knee, ankle or foot.

Exclusion Criteria

• Surgery recommended as primary treatment intervention for CBP
• Current diagnosis of fibromyalgia
• Current substance use disorder other than nicotine.
• Psychiatric disorder and not on a stable pharmacologic regimen for ≥ 4 weeks prior to screening
• Opiate use daily
• Currently pregnant or breast feeding.
• Unable to understand the consent form.
• History of head injury with loss of consciousness for more than 5 minutes, seizures, history of stroke, brain surgery, brain tumor, multiple sclerosis.
• History of metastatic cancer, rheumatoid arthritis, polymyalgia rheumatica, scleroderma, lupus, or polymyositis
• Unintended weight loss of 20 pounds or more in the last year
• Cauda equina syndrome
• Ferromagnetic implants or other contraindications for MRI
• Uncompensated congestive heart failure, unstable angina, poorly controlled arrhythmia, active systemic infection end stage renal disease.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

Evan Evan Lindeman, MS

Role: CONTACT

evan.lindeman@va.gov

Facility Contacts

Mary R Lee, MD

Role: primary

mary.lee3@va.gov

202-745-8000 ext. 58128

Evan Lindeman, MS

Role: backup

evan.lindeman@va.gov

Other Identifiers

1781312

Identifier Type: -

Identifier Source: org_study_id