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

NCT06906211 | Recruiting DMC FDA Device

• 1 other identifier: 1781312
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Back Pain; Chronic Pain (Back / Neck)

Keywords

low intensity focused ultrasound; chronic back pain; chronic pain; functional magnetic resonance imaging

Outcome Measures

Primary Outcomes (3)

• Measures of Central Sensitization - Thermal Pain Threshold

  For the first measure, the probe is placed on the skin on the ventral aspect of the forearm on the nondominant arm. The temperature is set at 32°C and the temperature is increased at a rate of 1°C/s to a maximum of 52°C. Participants will be asked to press a button when the heat reaches a painful level. The outcome is the temperature at this level. Heat PT are averaged over three trials each separated by 40 seconds. Thermal PT will be performed prior to and after LIFU. On each trial, the thermode is moved to a different site on the forearm to avoid sensitization and response suppression of cutaneous heat receptors.

  immediately prior to 1 session LIFU and within 1 hour post LIFU; immediately prior to 1 session sham and with in 1 hour post shamdays

• Measures of Central Sensitization - Temporal Summation of Pain

  The second measure refers to the perception of increasing pain in response to repeated same noxious stimuli delivered at a frequency of \> 0.33 Hz. Temporal summation of pain serves as a proxy measure of pain facilitation and CS. Individuals with enhanced temporal summation of pain have facilitated ascending nociceptive processing and reduced pain-modulatory capacities. Following the temporal summation of pain paradigm, three stimulus trains of trapezoid heat pulses of 1.5 s duration will be delivered to the dorsum of the dominant hand at an inter-pulse interval of 2.5 seconds at individual subject heat pain of 6/10 on numeric pain rating scale. A total of 5 stimuli will be delivered per train. Participants will be required to rate each stimulus (0-10). The Δ scores from 5th to 1st stimulus of each train will be averaged.

  immediately prior to 1 session LIFU and within 1 hour post LIFU; immediately prior to 1 session sham and with in 1 hour post shamdays

• Measures of Central Sensitization - Conditioned Modulation of Pain

  A type of counter-irritation paradigm that can be used as a proxy measure for descending anti-nociceptive or pain modulation activity. CPM involves presentation of a conditioning pain stimulus to a remote area of the body while a nociceptive (test) stimulus (TS) is applied to the contralateral (heterotopic) area. We will employ conditioned modulation of pain according to using a sequential conditioning-test stimulus protocol as recommended by. The test stimulus consists of a two-minute thermal stimulus applied with the thermode at a rating of 5/10 on the numeric pain rating scale. Participants will rate their perceived pain (0-10, numeric pain rating scale) every 15 seconds. This will be performed pre/post the conditioning stimulus. The conditioning stimulus will be a cold pressor test.. The non-dominant arm will be immersed in a cold-water bath (12°C) for two minutes. This method recruits inhibitory conditioned modulation of pain because it is a strong nociceptive stimulation.

  immediately prior to 1 session LIFU and within 1 hour post LIFU; immediately prior to 1 session sham and with in 1 hour post shamdays

Secondary Outcomes (2)

• Neurologic Pain Signature

  immediately prior to 1 session LIFU and within 1 hour post LIFU; immediately prior to 1 session sham and with in 1 hour post shamdays

• Tonic Pain Signature

  immediately prior to 1 session LIFU and within 1 hour post LIFU; immediately prior to 1 session sham and with in 1 hour post sham

Study Arms (2)

LIFU/Sham

OTHER

double-blind, sham-controlled, crossover study in N=66 individuals with Chronic Back Pain

Device: low intensity focused ultrasound (LIFU)

Sham/LIFU

OTHER

double-blind, sham-controlled, crossover study in N=66 individuals with Chronic Back Pain

Device: low intensity focused ultrasound (LIFU)

Interventions

low intensity focused ultrasound (LIFU) 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.

LIFU/Sham; Sham/LIFU

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington D.C. Veterans Affairs Medical Center: lead

Study Sites (1)

Washington DC Veterans Affairs Medical Center

Washington D.C., District of Columbia, 20422, United States

RECRUITING

MeSH Terms

Conditions

Chronic Pain

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Mary R Lee, MD

  Washington D.C. Veterans Affairs Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mary R Lee, MD

CONTACT

202-745-8000; mary.lee3@va.gov

Evan Evan Lindeman, MS

CONTACT

evan.lindeman@va.gov

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The Sham condition will be conducted using an interface which does not allow ultrasound energy to pass from the transducer to the target. The administration of LIFU/sham will be conducted in a double-blind fashion.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: within-subject, randomized, double-blind, sham-controlled trial

Study Record Dates

• First Submitted: February 13, 2025
• First Posted: April 2, 2025
• Study Start: January 15, 2025
• Primary Completion (Estimated): January 26, 2028
• Study Completion (Estimated): January 26, 2028
• Last Updated: April 2, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, ANALYTIC CODE
• Time Frame: data will be available after analysis of primary and secondary outcomes are completed

Locations

US (1)