Deep Brain Therapy With Low-intensity Ultrasound for Generalized Chronic Pain (DBT)

Deep Brain Therapy With Low-intensity Ultrasound for Generalized Chronic Pain: A Pilot Study of Target Engagement and Analgesic Effects

This study will evaluate a new form of non-invasive deep brain therapy for individuals with generalized chronic pain. Low-intensity transcranial focused ultrasound stimulation will first be delivered using a range of stimulation parameters during psychophysical and physiological monitoring. A well-tolerated stimulation protocol will be selected for subsequent testing in a blinded randomized sham-controlled cross-over trial. The trial will evaluate brain target engagement using magnetic resonance imaging and CVAS and PROMIS numerical rating scales of pain.

Study Overview

• Status: Completed
• Conditions: Chronic Pain; Chronic Pain Syndrome; Widespread Chronic Pain
• Intervention / Treatment: Device: Verum stimulation with Diadem prototype; Device: Sham stimulation with Diadem prototype

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18-65, any gender
2. Primary diagnosis of generalized chronic pain or widespread chronic pain.
3. Moderate-to-severe chronic pain lasting at least 2 months
4. Stated willingness to comply with all study procedures and avoid changes to current treatments (medications, physical therapy, cognitive behavioral therapy) for the duration of the study
5. For females of reproductive potential: negative pregnancy test or use of highly effective contraception for at least 1 month prior to baseline; agreement to use such a method throughout the study
6. Capacity to provide informed consent; provision of a signed and dated consent form

Exclusion Criteria:

1. History of serious brain injury or other neurologic disorder
2. Poorly managed general medical condition
3. Pregnant or breast feeding
4. Implanted device in the head or neck
5. MRI intolerance or contraindication
6. Brain stimulation (e.g., VNS, TMS) in the past month
7. Lifetime history of a serious suicide attempt (Hooley et al., 2014)
8. Clinically inappropriate for participation in the study as determined by the study team

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active stimulation; Low-intensity transcranial focused ultrasound stimulation of deep brain targets involved in pain perception Intervention: Device: Diadem prototype	Device: Verum stimulation with Diadem prototype; Diadem prototype device delivers focused low-intensity ultrasound stimulation
Sham Comparator: Sham stimulation; Low-intensity transcranial focused ultrasound stimulation using unfocused wave Intervention: Device: Diadem prototype	Device: Sham stimulation with Diadem prototype; Diadem prototype device delivers active sham, unfocused low-intensity ultrasound stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Target engagement: brain activation	MRI quantification of blood oxygenation level dependent (BOLD) activation.	1 day At MRI study visit
Target engagement: brain connectivity	Pearson's correlation of BOLD signals between the stimulated target and connected regions.	1 day At MRI study visit
Pain intensity: momentary change	Computerized Visual Analogue Scale. The scale is measured using a continuous slider. At its left boundary, the slider indicates no pain (score 0). At its right boundary, the slider indicates worst pain imaginable (score 100). A lower score indicates a better treatment outcome.	1 day At stimulation visit
Pain intensity: subjective state	PROMIS scale of pain intensity. Scores range from 1 (no pain) to 5 (severe pain). A lower score indicates a better treatment outcome.	1 day At stimulation visit
Depression scale: subjective state	PROMIS scale of depression. Scores range from 1 (not at all depressed) to 5 (severely depressed). A lower score indicates a better treatment outcome.	1 day At stimulation visit
Anxiety scale: subjective state	PROMIS scale of anxiety. Scores range from 1 (not at all anxious) to 5 (severely anxious). A lower score indicates a better treatment outcome.	1 day At stimulation visit

Collaborators and Investigators

• Sponsor: University of Utah

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2023
• Primary Completion (Actual): August 28, 2024
• Study Completion (Actual): August 28, 2024

Study Registration Dates

• First Submitted: January 3, 2023
• First Submitted That Met QC Criteria: January 4, 2023
• First Posted (Actual): January 9, 2023

Study Record Updates

• Last Update Posted (Actual): May 25, 2025
• Last Update Submitted That Met QC Criteria: May 20, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Chronic Pain
• Other Study ID Numbers: IRB_00162656

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No