Chronic PainNCT07910396
Focused Ultrasound Neuromodulation for Chronic Pain
A study testing Focused PCM-Guided CMN LIFU in people with Chronic Pain and Sickle Cell Disease, run by University of Minnesota at 1 site in United States.
Trial summary
This study will evaluate the feasibility, tolerability, and preliminary analgesic effects of individualized Precision Confidence Mapping-guided low-intensity focused ultrasound neuromodulation in adults with chronic pain. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Pain, Sickle Cell Disease, Chronic Pelvic Pain Syndrome
- What is being tested?
- Focused PCM-Guided CMN LIFU
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Jan 2027to 29 Dec 2032
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 years or older at the time of enrollment
- Able to provide written informed consent
- Able to read and communicate verbally and in writing in English
- Able and willing to comply with all study procedures, including MRI, LIFU sessions, remote REDCap questionnaires, and daily pain diary completion
- Chronic pain of any etiology, defined as pain present for at least 3 months
- Average pain intensity of at least 3 out of 10 on the Numeric Rating Scale over the prior 4 weeks or based on participant report during screening
- Stable pain medication regimen for at least 2 weeks prior to the first LIFU session, when clinically feasible
Who cannot join
- Standard MRI contraindications, including ferromagnetic implants, pacemaker or other non-MRI-compatible implanted devices, cochlear implant, intracranial aneurysm clip, retained metallic foreign body, or other MRI-incompatible device or condition
- Inability of the participant's head to fit within the MRI head coil while wearing the MR-compatible device
- Inability to tolerate MRI scanning, including severe claustrophobia not manageable with standard non-sedating accommodations
- Implanted metallic hardware in the skull, scalp, or temporal bone that would interfere with LIFU targeting or acoustic transmission
- Sacral neuromodulation implant
- Scalp wound, dermatologic condition, or local sensitivity over the temporal window region that would interfere with safe device placement or acoustic coupling
Show all 29Show fewer
- Inability to tolerate the LIFU device setup, including headgear placement, acoustic coupling gel, or the 60-minute session duration
- Pregnancy or current breastfeeding
- Acute pain episode, vaso-occlusive crisis, injury, infection, or other acute medical event at the time of screening, MRI, or planned LIFU stimulation that requires emergency evaluation, hospitalization, or a major change in pain treatment
- Major starting, stopping, or dose escalation of pain medications or other medications likely to substantially affect pain ratings during the baseline monitoring period or immediately before planned LIFU stimulation
- Severe functional neurological deficit from prior stroke, central nervous system lesion, or other neurological condition that, in the judgment of the PI, would interfere with study participation, interpretation of study outcomes, or participant safety
- Diagnosed epilepsy or prior seizure
- History of head trauma diagnosed as concussion, if in the judgment of the PI the event or residual symptoms could increase risk, interfere with study participation, or compromise interpretation of study outcomes
- Current use of, or recent withdrawal from, medications that can increase seizure risk, if in the judgment of the PI this would increase risk from study participation
- Active central nervous system infection, active inflammatory central nervous system disease, or other unstable neurological disorder
- Unstable medical or psychiatric condition that, in the judgment of the PI, would increase risk, interfere with study participation, or compromise interpretation of study outcomes
- Current substance use disorder, other than nicotine, alcohol, or cannabis use, that in the judgment of the PI would interfere with participation or safety
- Participation in another interventional clinical trial that could interfere with study outcomes or participant safety
- Any other clinically significant condition or circumstance that, in the judgment of the PI, would create an unacceptable risk to the participant, prevent completion of required study procedures, or substantially compromise interpretation of study outcomes
- Children
- Pregnant women/persons
- Fetuses
- Neonates
- Prisoners
- Adults lacking capacity to consent or adults with diminished or fluctuating capacity to consent
- Non-English speakers
- Individuals unable to read
- Students of the researcher
- Individuals approached during a stressful situation, such as emergency care, childbirth, or another crisis setting
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Masonic Institute for the Developing Brain
Minneapolis, Minnesota, 55414
Julian Sergej Ramirez, 206-491-6130, ramirezj@umn.edu
About this study
Official title: Stimulating Somato-Cognitive Action Network With Low-Intensity Focused Ultrasound in Chronic Pain
This study will evaluate the feasibility, tolerability, and preliminary analgesic effects of individualized Precision Confidence Mapping-guided low-intensity focused ultrasound neuromodulation in adults with chronic pain.
Participants will undergo MRI and resting-state fMRI to identify an individualized SCAN-connected centromedian thalamic target. Participants will then complete two treatment arms in randomized order: focused centromedian thalamic low-intensity focused ultrasound and unfocused control low-intensity focused ultrasound. Each treatment arm includes five consecutive daily stimulation sessions, separated by a washout interval.
The primary outcome is change in daily pain intensity measured using Brief Pain Inventory pain intensity items. Secondary outcomes include pain-related symptoms, physical function, fatigue, sleep disturbance, depressive symptoms, anxiety symptoms, pain catastrophizing, pain vigilance, neuropathic pain features, feasibility, tolerability, adverse events, blinding integrity, and exploratory neuroimaging measures.
Read the detailed description
This is a single-site, double-blind, randomized, two-condition crossover feasibility trial evaluating Precision Confidence Mapping-guided low-intensity focused ultrasound neuromodulation in adults with chronic pain.
The study will enroll adults with chronic pain of any etiology, defined as pain present for at least 3 months. The study is designed to include participants across multiple chronic pain populations, including sickle cell disease and chronic pelvic, bladder, or other chronic pain conditions.
Participants will complete an initial screening and a baseline visit that includes informed consent, medical and pain history, baseline questionnaires, MRI safety screening, and 3T MRI. MRI acquisition will include structural imaging, PETRA/pseudo-CT imaging for skull and acoustic modeling, and resting-state fMRI for individualized functional network mapping. Precision Confidence Mapping will be used to identify each participant's individualized SCAN-connected centromedian thalamic target. If an individualized target cannot be identified with sufficient confidence, a probabilistic atlas-based centromedian thalamic target may be used as a fallback.
Participants will then complete two treatment arms in randomized order. In one arm, focused low-intensity focused ultrasound will be delivered to the individualized SCAN-connected centromedian thalamic target using the Attune Neurosciences ATTN201 device. In the other arm, unfocused control low-intensity focused ultrasound will be delivered using the same device placement, acoustic gel application, pulse timing, session duration, and operator interactions, but with randomized element delays designed to minimize focal pressure at the target. Each arm includes five consecutive daily 60-minute sessions.
The two treatment arms will be separated by a washout interval of at least 14 days and up to 90 days. Participants will complete daily pain diaries before, during, and after each treatment arm. The primary analysis will compare within-participant change in daily pain intensity after focused CMN LIFU versus unfocused control LIFU. Secondary and exploratory outcomes will assess pain interference, function, fatigue, sleep, mood, anxiety, pain catastrophizing, neuropathic pain features, feasibility, tolerability, adverse events, blinding integrity, and neuroimaging features associated with treatment response.
- Being tested
- Focused PCM-Guided CMN LIFU, Unfocused Control LIFU
- Keywords
- Low-intensity focused ultrasound, Chronic pain, Focused ultrasound, Neuromodulation, Brief Pain Inventory
- Medical subject headings
- Chronic Pain, Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Focused PCM-Guided CMN LIFUDevice
Also called Focused Centromedian Thalamic Low-Intensity Focused Ultrasound, ATTN201 Low-Intensity Focused Ultrasound System
Focused low-intensity focused ultrasound will be delivered using the Attune Neurosciences ATTN201 device to an individualized SCAN-connected centromedian thalamic target identified from resting-state fMRI using Precision Confidence Mapping. Stimulation will be delivered once daily for five consecutive treatment days.
Unfocused Control LIFUDevice
Also called Unfocused Control Low-Intensity Focused Ultrasound
Unfocused control low-intensity focused ultrasound will use the same device placement, acoustic gel application, pulse timing, session duration, and five-day treatment schedule as focused stimulation. Randomized element delays will be used to produce diffuse acoustic output and negligible focal pressure at the intended deep brain target.
| Study group | Role | What they receive |
|---|---|---|
| Focused CMN LIFU First, Then Unfocused Control LIFU | Experimental | Participants randomized to this sequence will receive focused PCM-guided centromedian thalamic low-intensity focused ultrasound once daily for five consecutive treatment days during Arm 1, followed by a washout interval, then unfocused control low-intensity focused ultrasound once daily for five consecutive treatment days during Arm 2. Receives: Device: Focused PCM-Guided CMN LIFU; Device: Unfocused Control LIFU |
| Unfocused Control LIFU First, Then Focused CMN LIFU | Experimental | Participants randomized to this sequence will receive unfocused control low-intensity focused ultrasound once daily for five consecutive treatment days during Arm 1, followed by a washout interval, then focused PCM-guided centromedian thalamic low-intensity focused ultrasound once daily for five consecutive treatment days during Arm 2. Receives: Device: Focused PCM-Guided CMN LIFU; Device: Unfocused Control LIFU |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Daily Pain Intensity
Daily pain intensity will be measured using the Brief Pain Inventory pain intensity items. The daily pain intensity composite will be calculated as the mean of four 0 to 10 ratings: current pain, worst pain, least pain, and average pain over the past 24 hours. The primary analysis will compare within-participant change in daily pain intensity after focused PCM-guided CMN LIFU versus unfocused control LIFU.
Measured: Pre-arm baseline through Days 6 to 7 after each 5-day treatment arm
Secondary outcomes (18)
Change in Pain Interference Measured by the Brief Pain Inventory (BPI) Pain Interference Subscale
Pain interference will be measured with the 7-item Pain Interference subscale of the Brief Pain Inventory, covering general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life over the past week. Each item is rated from 0 (does not interfere) to 10 (completely interferes). The outcome is the mean of the 7 items (range 0-10). Higher scores indicate greater pain interference. Change is calculated as Day 7 minus the pre-arm baseline for each treatment condition.
Measured: Pre-Arm 1 baseline, Day 7 of Arm 1, pre-Arm 2 baseline (after the 14 to 90 day washout), and Day 7 of Arm 2
Change in Physical Function Measured by the PROMIS Physical Function Short Form 6b T-Score
Physical function will be measured with the Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form v2.0 Physical Function 6b, 6 items each scored 1 to 5 (raw score range 6 to 30). Item responses will be converted to a standardized T-score (U.S. general population mean 50, standard deviation 10). Higher scores indicate better physical function (better outcome). Change will be calculated from the pre-arm baseline to Day 7 of the same arm (approximately 2 days after the fifth session) and compared between focused CMN LIFU and unfocused control LIFU.
Measured: Pre-Arm 1 baseline, Day 7 of Arm 1, pre-Arm 2 baseline (after the 14 to 90 day washout), and Day 7 of Arm 2
Change in Fatigue Measured by the PROMIS Fatigue Short Form 13a T-Score
Fatigue will be measured with the Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form v1.0 Fatigue 13a (FACIT-Fatigue), 13 items with a 7-day recall, each scored 1 to 5 (raw score range 13 to 65). Item responses will be converted to a standardized T-score (U.S. general population mean 50, standard deviation 10). Higher scores indicate more fatigue (worse outcome). Change will be calculated from the pre-arm baseline to Day 7 of the same arm (approximately 2 days after the fifth session) and compared between focused CMN LIFU and unfocused control LIFU.
Measured: Pre-Arm 1 baseline, Day 7 of Arm 1, pre-Arm 2 baseline (after the 14 to 90 day washout), and Day 7 of Arm 2
Change in Insomnia Severity Measured by the Insomnia Severity Index (ISI) Total Score
Insomnia severity will be measured with the 7-item Insomnia Severity Index, administered with a 7-day recall period. Each item is rated from 0 to 4, and the total score ranges from 0 to 28. Higher scores indicate more severe insomnia (worse outcome). Change will be calculated from the pre-arm baseline to Day 7 of the same arm (approximately 2 days after the fifth session) and compared between focused CMN LIFU and unfocused control LIFU.
Measured: Pre-Arm 1 baseline, Day 7 of Arm 1, pre-Arm 2 baseline (after the 14 to 90 day washout), and Day 7 of Arm 2
Change in Depressive Symptoms Measured by the Patient Health Questionnaire-8 (PHQ-8) Total Score
Depressive symptoms will be measured with the 8-item Patient Health Questionnaire- 8, which asks about the past 2 weeks. Each item is rated from 0 (not at all) to 3 (nearly every day), and the total score ranges from 0 to 24. Higher scores indicate more severe depressive symptoms (worse outcome). Change will be calculated from the pre-arm baseline to Day 7 of the same arm (approximately 2 days after the fifth session) and compared between focused CMN LIFU and unfocused control LIFU.
Measured: Pre-Arm 1 baseline, Day 7 of Arm 1, pre-Arm 2 baseline (after the 14 to 90 day washout), and Day 7 of Arm 2
Change in Anxiety Symptoms Measured by the Generalized Anxiety Disorder-7 (GAD-7) Total Score
Anxiety symptoms will be measured with the 7-item Generalized Anxiety Disorder-7 scale, which asks about the past 2 weeks. Each item is rated from 0 (not at all) to 3 (nearly every day), and the total score ranges from 0 to 21. Higher scores indicate more severe anxiety symptoms (worse outcome). Change will be calculated from the pre-arm baseline to Day 7 of the same arm (approximately 2 days after the fifth session) and compared between focused CMN LIFU and unfocused control LIFU.
Measured: Pre-Arm 1 baseline, Day 7 of Arm 1, pre-Arm 2 baseline (after the 14 to 90 day washout), and Day 7 of Arm 2
Change in Pain Catastrophizing Measured by the Pain Catastrophizing Scale (PCS) Total Score
Pain catastrophizing will be measured with the 13-item Pain Catastrophizing Scale. Each item is rated from 0 (not at all) to 4 (all the time), and the total score ranges from 0 to 52. Higher scores indicate greater pain catastrophizing (worse outcome). Change will be calculated from the pre-arm baseline to Day 7 of the same arm (approximately 2 days after the fifth session) and compared between focused CMN LIFU and unfocused control LIFU.
Measured: Pre-Arm 1 baseline, Day 7 of Arm 1, pre-Arm 2 baseline (after the 14 to 90 day washout), and Day 7 of Arm 2
Change in Pain Vigilance Measured by the Pain Vigilance and Awareness Questionnaire (PVAQ) Total Score
Attention to pain will be measured with the 16-item Pain Vigilance and Awareness Questionnaire. Each item is rated from 0 (never) to 5 (always), with 2 items reverse-scored, and the total score ranges from 0 to 80. Higher scores indicate greater vigilance and awareness of pain (worse outcome). Change will be calculated from the pre-arm baseline to Day 7 of the same arm
(approximately 2 days after the fifth session) and compared between focused CMN LIFU and unfocused control LIFU.
Measured: Pre-Arm 1 baseline, Day 7 of Arm 1, pre-Arm 2 baseline (after the 14 to 90 day washout), and Day 7 of Arm 2
Change in Neuropathic Pain Symptoms Measured by the Neuropathic Pain Symptom Inventory (NPSI) Total Intensity Score
Neuropathic pain symptoms will be measured with the Neuropathic Pain Symptom Inventory. The total intensity score is the sum of the 10 symptom descriptor items, each rated from 0 (none) to 10 (worst imaginable), giving a range of 0 to 100. The 2 items on duration and number of pain attacks are not part of the total score. Higher scores indicate more severe neuropathic pain symptoms (worse outcome). Change will be calculated from the pre-arm baseline to Day 7 of the same arm (approximately 2 days after the fifth session) and compared between focused CMN LIFU and unfocused control LIFU.
Measured: Pre-Arm 1 baseline, Day 7 of Arm 1, pre-Arm 2 baseline (after the 14 to 90 day washout), and Day 7 of Arm 2
Within-Session Change in Pain Intensity Measured by a 100 mm Visual Analog Scale (VAS)
Current pain will be rated on a 100 mm Visual Analog Scale, from 0 mm (no pain) to 100 mm (worst pain imaginable), before stimulation (0 minutes) and at 20, 40 and 60 minutes of each LIFU session. Higher scores indicate more pain (worse outcome). Within-session change is the 60-minute rating minus the 0-minute rating (range -100 to 100 mm; negative values indicate pain reduction), averaged across the 5 sessions of each treatment arm and compared between focused CMN LIFU and unfocused control LIFU.
Measured: 0 (pre-stimulation), 20, 40 and 60 minutes during each LIFU session on Days 1 to 5 of Arm 1 and Days 1 to 5 of Arm 2
Rate of Enrollment (Participants Enrolled per Month)
Number of participants who sign informed consent divided by the number of months of active recruitment.
Measured: From the start of recruitment through enrollment of the final participant (target enrollment 80)
Percentage of Randomized Participants Who Complete the Study
Percentage of randomized participants who complete both treatment arms and the Day 7 assessment after Arm 2.
Measured: From randomization through Day 7 of Arm 2, an average of 4 to 6 months (up to 12 months)
Percentage of Scheduled LIFU Sessions Completed
Number of 60-minute LIFU sessions completed in full divided by the number of sessions scheduled (10 per randomized participant: 5 focused CMN LIFU and 5 unfocused control LIFU), expressed as a percentage and reported by condition.
Measured: Days 1 to 5 of Arm 1 and Days 1 to 5 of Arm 2
Number of Participants Who Complete All 10 LIFU Sessions
Number and percentage of randomized participants who complete all 5 sessions in both treatment arms.
Measured: Days 1 to 5 of Arm 1 and Days 1 to 5 of Arm 2, up to 12 months
Percentage of Expected Daily Pain Diary Entries Completed
Number of completed daily Pain Diary entries (Brief Pain Inventory pain intensity items, 4 items) divided by the number of expected daily entries for each participant, expressed as a percentage.
Measured: From the day after Visit 1 through the end of post-Arm 2 pain monitoring, an average of 4 to 6 months (up to 12 months)
Number of Participants With an Individualized PCM-Derived SCAN-Connected CMN Target
Number of participants with usable baseline MRI for whom Precision Confidence Mapping identifies an individualized SCAN-connected centromedian nucleus (CMN) target. Participants without an individualized target may receive an atlas-based fallback target. The outcome reports the number of participants for whom an individualized target was successfully identified.
Measured: Baseline, after Visit 1 MRI processing (approximately 1 to 2 weeks after Visit 1)
Adverse Events and Device Tolerability
Adverse events and tolerability will be assessed using pre-session and post-session symptom checklists, participant reports, and PI review of adverse event severity, seriousness, expectedness, and relatedness to study procedures.
Measured: From consent through final post-treatment monitoring, up to 12 months per participant
Number of Participants Who Correctly Identify Their Treatment Condition
At the end of the fifth session of each treatment arm, participants will be asked whether they believe they received focused or unfocused stimulation during that arm (focused, unfocused, or don't know). The number and percentage of participants whose guess matches their actual assignment will be reported separately for the focused CMN LIFU arm and the unfocused control LIFU arm.
Measured: Day 5 of Arm 1 and Day 5 of Arm 2 (immediately after the fifth LIFU session)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2026
- Study start4 Jan 2027 (estimated)
- Primary completion29 Dec 2032 (estimated)
- Study completion29 Dec 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic PainStudies of the same condition, open and under way.
- More trials run by University of MinnesotaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Participants will complete two treatment arms in a randomized crossover design. In one arm, participants will receive focused Precision Confidence Mapping-guided low-intensity focused ultrasound targeting the individualized SCAN-connected centromedian thalamic coordinate. In the other arm, participants will receive unfocused control low-intensity focused ultrasound. Each treatment arm includes five consecutive daily sessions, with a washout interval between arms.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Oscar Miranda Dominguez, PhD, Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07910396
- Sponsor's protocol ID
- STUDY00028828
- Status last verified
- Oct 2026
- First submitted
- 7 Oct 2026
- Last updated
- 2 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Stimulating Somato-Cognitive Action Network With Low-Intensity Focused Ultrasound in Chronic Pain
- ClinicalTrials.gov ID
- NCT07910396
- Acronym / sponsor ID
- STUDY00028828
- Keywords
- Low-intensity focused ultrasound, Chronic pain, Focused ultrasound, Neuromodulation, Brief Pain Inventory
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Study start
- 4 Jan 2027 (estimated)
- Primary completion
- 29 Dec 2032 (estimated)
- Study completion
- 29 Dec 2032 (estimated)
- First posted
- 2 Nov 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the feasibility, tolerability, and preliminary analgesic effects of individualized Precision Confidence Mapping-guided low-intensity focused ultrasound neuromodulation in adults with chronic pain.
Participants will undergo MRI and resting-state fMRI to identify an individualized SCAN-connected centromedian thalamic target. Participants will then complete two treatment arms in randomized order: focused centromedian thalamic low-intensity focused ultrasound and unfocused control low-intensity focused ultrasound. Each treatment arm includes five consecutive daily stimulation sessions, separated by a washout interval.
The primary outcome is change in daily pain intensity measured using Brief Pain Inventory pain intensity items. Secondary outcomes include pain-related symptoms, physical function, fatigue, sleep disturbance, depressive symptoms, anxiety symptoms, pain catastrophizing, pain vigilance, neuropathic pain features, feasibility, tolerability, adverse events, blinding integrity, and exploratory neuroimaging measures.
Detailed description
This is a single-site, double-blind, randomized, two-condition crossover feasibility trial evaluating Precision Confidence Mapping-guided low-intensity focused ultrasound neuromodulation in adults with chronic pain.
The study will enroll adults with chronic pain of any etiology, defined as pain present for at least 3 months. The study is designed to include participants across multiple chronic pain populations, including sickle cell disease and chronic pelvic, bladder, or other chronic pain conditions.
Participants will complete an initial screening and a baseline visit that includes informed consent, medical and pain history, baseline questionnaires, MRI safety screening, and 3T MRI. MRI acquisition will include structural imaging, PETRA/pseudo-CT imaging for skull and acoustic modeling, and resting-state fMRI for individualized functional network mapping. Precision Confidence Mapping will be used to identify each participant's individualized SCAN-connected centromedian thalamic target. If an individualized target cannot be identified with sufficient confidence, a probabilistic atlas-based centromedian thalamic target may be used as a fallback.
Participants will then complete two treatment arms in randomized order. In one arm, focused low-intensity focused ultrasound will be delivered to the individualized SCAN-connected centromedian thalamic target using the Attune Neurosciences ATTN201 device. In the other arm, unfocused control low-intensity focused ultrasound will be delivered using the same device placement, acoustic gel application, pulse timing, session duration, and operator interactions, but with randomized element delays designed to minimize focal pressure at the target. Each arm includes five consecutive daily 60-minute sessions.
The two treatment arms will be separated by a washout interval of at least 14 days and up to 90 days. Participants will complete daily pain diaries before, during, and after each treatment arm. The primary analysis will compare within-participant change in daily pain intensity after focused CMN LIFU versus unfocused control LIFU. Secondary and exploratory outcomes will assess pain interference, function, fatigue, sleep, mood, anxiety, pain catastrophizing, neuropathic pain features, feasibility, tolerability, adverse events, blinding integrity, and neuroimaging features associated with treatment response.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants will complete two treatment arms in a randomized crossover design. In one arm, participants will receive focused Precision Confidence Mapping-guided low-intensity focused ultrasound targeting the individualized SCAN-connected centromedian thalamic coordinate. In the other arm, participants will receive unfocused control low-intensity focused ultrasound. Each treatment arm includes five consecutive daily sessions, with a washout interval between arms.
| Arm | Type | Receives |
|---|---|---|
| Focused CMN LIFU First, Then Unfocused Control LIFU | Experimental | Device: Focused PCM-Guided CMN LIFU, Device: Unfocused Control LIFUParticipants randomized to this sequence will receive focused PCM-guided centromedian thalamic low-intensity focused ultrasound once daily for five consecutive treatment days during Arm 1, followed by a washout interval, then unfocused control low-intensity focused ultrasound once daily for five consecutive treatment days during Arm 2. |
| Unfocused Control LIFU First, Then Focused CMN LIFU | Experimental | Device: Focused PCM-Guided CMN LIFU, Device: Unfocused Control LIFUParticipants randomized to this sequence will receive unfocused control low-intensity focused ultrasound once daily for five consecutive treatment days during Arm 1, followed by a washout interval, then focused PCM-guided centromedian thalamic low-intensity focused ultrasound once daily for five consecutive treatment days during Arm 2. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age 18 years or older at the time of enrollment
- Able to provide written informed consent
- Able to read and communicate verbally and in writing in English
- Able and willing to comply with all study procedures, including MRI, LIFU sessions, remote REDCap questionnaires, and daily pain diary completion
- Chronic pain of any etiology, defined as pain present for at least 3 months
Key exclusion criteria (29 listed)
- Standard MRI contraindications, including ferromagnetic implants, pacemaker or other non-MRI-compatible implanted devices, cochlear implant, intracranial aneurysm clip, retained metallic foreign body, or other MRI-incompatible device or condition
- Inability of the participant's head to fit within the MRI head coil while wearing the MR-compatible device
- Inability to tolerate MRI scanning, including severe claustrophobia not manageable with standard non-sedating accommodations
- Implanted metallic hardware in the skull, scalp, or temporal bone that would interfere with LIFU targeting or acoustic transmission
- Sacral neuromodulation implant
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Focused PCM-Guided CMN LIFUAlso: Focused Centromedian Thalamic Low-Intensity Focused Ultrasound, ATTN201 Low-Intensity Focused Ultrasound SystemFocused low-intensity focused ultrasound will be delivered using the Attune Neurosciences ATTN201 device to an individualized SCAN-connected centromedian thalamic target identified from resting-state fMRI using Precision Confidence Mapping. Stimulation will be delivered once daily for five consecutive treatment days. | Device | Focused CMN LIFU First, Then Unfocused Control LIFU, Unfocused Control LIFU First, Then Focused CMN LIFU |
| Unfocused Control LIFUAlso: Unfocused Control Low-Intensity Focused UltrasoundUnfocused control low-intensity focused ultrasound will use the same device placement, acoustic gel application, pulse timing, session duration, and five-day treatment schedule as focused stimulation. Randomized element delays will be used to produce diffuse acoustic output and negligible focal pressure at the intended deep brain target. | Device | Focused CMN LIFU First, Then Unfocused Control LIFU, Unfocused Control LIFU First, Then Focused CMN LIFU |
Primary outcome
Change in Daily Pain Intensity
Time frame: Pre-arm baseline through Days 6 to 7 after each 5-day treatment arm
Daily pain intensity will be measured using the Brief Pain Inventory pain intensity items. The daily pain intensity composite will be calculated as the mean of four 0 to 10 ratings: current pain, worst pain, least pain, and average pain over the past 24 hours. The primary analysis will compare within-participant change in daily pain intensity after focused PCM-guided CMN LIFU versus unfocused control LIFU.
18 secondary outcomes
Change in Pain Interference Measured by the Brief Pain Inventory (BPI) Pain Interference Subscale
Time frame: Pre-Arm 1 baseline, Day 7 of Arm 1, pre-Arm 2 baseline (after the 14 to 90 day washout), and Day 7 of Arm 2
Change in Physical Function Measured by the PROMIS Physical Function Short Form 6b T-Score
Time frame: Pre-Arm 1 baseline, Day 7 of Arm 1, pre-Arm 2 baseline (after the 14 to 90 day washout), and Day 7 of Arm 2
Change in Fatigue Measured by the PROMIS Fatigue Short Form 13a T-Score
Time frame: Pre-Arm 1 baseline, Day 7 of Arm 1, pre-Arm 2 baseline (after the 14 to 90 day washout), and Day 7 of Arm 2
Change in Insomnia Severity Measured by the Insomnia Severity Index (ISI) Total Score
Time frame: Pre-Arm 1 baseline, Day 7 of Arm 1, pre-Arm 2 baseline (after the 14 to 90 day washout), and Day 7 of Arm 2
Change in Depressive Symptoms Measured by the Patient Health Questionnaire-8 (PHQ-8) Total Score
Time frame: Pre-Arm 1 baseline, Day 7 of Arm 1, pre-Arm 2 baseline (after the 14 to 90 day washout), and Day 7 of Arm 2
Change in Anxiety Symptoms Measured by the Generalized Anxiety Disorder-7 (GAD-7) Total Score
Time frame: Pre-Arm 1 baseline, Day 7 of Arm 1, pre-Arm 2 baseline (after the 14 to 90 day washout), and Day 7 of Arm 2
Change in Pain Catastrophizing Measured by the Pain Catastrophizing Scale (PCS) Total Score
Time frame: Pre-Arm 1 baseline, Day 7 of Arm 1, pre-Arm 2 baseline (after the 14 to 90 day washout), and Day 7 of Arm 2
Change in Pain Vigilance Measured by the Pain Vigilance and Awareness Questionnaire (PVAQ) Total Score
Time frame: Pre-Arm 1 baseline, Day 7 of Arm 1, pre-Arm 2 baseline (after the 14 to 90 day washout), and Day 7 of Arm 2
Change in Neuropathic Pain Symptoms Measured by the Neuropathic Pain Symptom Inventory (NPSI) Total Intensity Score
Time frame: Pre-Arm 1 baseline, Day 7 of Arm 1, pre-Arm 2 baseline (after the 14 to 90 day washout), and Day 7 of Arm 2
Within-Session Change in Pain Intensity Measured by a 100 mm Visual Analog Scale (VAS)
Time frame: 0 (pre-stimulation), 20, 40 and 60 minutes during each LIFU session on Days 1 to 5 of Arm 1 and Days 1 to 5 of Arm 2
Rate of Enrollment (Participants Enrolled per Month)
Time frame: From the start of recruitment through enrollment of the final participant (target enrollment 80)
Percentage of Randomized Participants Who Complete the Study
Time frame: From randomization through Day 7 of Arm 2, an average of 4 to 6 months (up to 12 months)
Percentage of Scheduled LIFU Sessions Completed
Time frame: Days 1 to 5 of Arm 1 and Days 1 to 5 of Arm 2
Number of Participants Who Complete All 10 LIFU Sessions
Time frame: Days 1 to 5 of Arm 1 and Days 1 to 5 of Arm 2, up to 12 months
Percentage of Expected Daily Pain Diary Entries Completed
Time frame: From the day after Visit 1 through the end of post-Arm 2 pain monitoring, an average of 4 to 6 months (up to 12 months)
Number of Participants With an Individualized PCM-Derived SCAN-Connected CMN Target
Time frame: Baseline, after Visit 1 MRI processing (approximately 1 to 2 weeks after Visit 1)
Adverse Events and Device Tolerability
Time frame: From consent through final post-treatment monitoring, up to 12 months per participant
Number of Participants Who Correctly Identify Their Treatment Condition
Time frame: Day 5 of Arm 1 and Day 5 of Arm 2 (immediately after the fifth LIFU session)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Oscar Miranda Dominguez, PhD principal investigator
University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Focused PCM-Guided CMN LIFU in people with Chronic Pain and Sickle Cell Disease, run by University of Minnesota at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Julian Sergej Benedikt Ramirez, PhD (206-491-6130, ramirezj@umn.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Daily Pain Intensity (time frame: Pre-arm baseline through Days 6 to 7 after each 5-day treatment arm). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2026.