FibromyalgiaNCT07226648
Ultrasonic Neuromodulation of Cingulate Cortex for Fibromyalgia
A study testing Focused Ultrasound in people with Fibromyalgia, run by SPIRE Therapeutics Inc. at 8 sites in United States.
Trial summary
The goal of this clinical trial is to evaluate a new noninvasive brain stimulation intervention for fibromyalgia and to determine its effectiveness in reducing pain. Participants will receive four treatments over the course of one month and will complete surveys at multiple time points throughout the 16-week study. Read more about this study
- Who is it for?
- Ages 22 years and older
- Conditions the study is for
- Fibromyalgia
- What is being tested?
- Focused Ultrasound
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 180 participants
- Where
- 8 sitesUnited States
- Study dates
- 11 Dec 2025to Dec 2026
- 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 22 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willing and able to provide informed consent.
- Age ≥ 22 years.
- Meets 2016 American College of Rheumatology criteria for fibromyalgia:
- Generalized pain, defined as pain in at least 4 of 5 regions, is present, AND
- Widespread pain index (WPI) ≥ 7 and symptom severity scale score (SSS) ≥ 5, or WPI of 4-6 and SSS score ≥ 9, AND
- Symptoms have been present at a similar level for at least 3 months, AND
Show all 40Show fewer
- A diagnosis of fibromyalgia is valid irrespective of other diagnoses. A diagnosis of fibromyalgia does not exclude the presence of other clinically important illnesses.
- Failure of at least two evidence-based medications or medications that are commonly used in clinical practice to treat fibromyalgia (e.g., pregabalin, duloxetine, milnacipran, sublingual cyclobenzaprine hydrochloride, tricyclics (e.g., amitriptyline, nortriptyline, desipramine),gabapentin, gabapentinoids, NSAIDS (including Cox-2 inhibitors), acetaminophen, SSRIs, SSNIs, muscle relaxants, non-sublingual forms of cyclobenzaprine hydrochloride, opioids, benzodiazepines), at least 1 of which is FDA-approved for the treatment of fibromyalgia (e.g., pregabalin, duloxetine, milnacipran, and sublingual cyclobenzaprine hydrochloride).
- Failure of one or more attempts at physical or Cognitive Behavioral Therapy (CBT) including:
- Aerobic exercise like walking, cycling, and swimming,
- Water therapy/hydrotherapy with warm water exercises,
- Tai Chi involving slow, controlled movements,
- Yoga,
- Resistance training,
- Bodyweight exercises,
- Pilates,
- Myofascial release therapy applying gentle pressure on trigger points,
- Massage therapy,
- Trigger point therapy targeting specific pain points,
- Joint mobilization,
- Postural retraining to correct body alignment,
- Balance and coordination exercises,
- Feldenkrais method for movement awareness,
- Alexander technique to enhance posture and movement efficiency,
- Transcutaneous Electrical Nerve Stimulation (TENS) for pain relief,
- Heat therapy using hot packs, infrared, or paraffin wax,
- Cold therapy with ice packs or cryotherapy,
- Ultrasound therapy for deep tissue relaxation,
- Biofeedback to control muscle tension and pain response,
- Gentle static stretching for prolonged duration,
- Active dynamic stretching for full range of motion,
- Proprioceptive Neuromuscular Facilitation (PNF) stretching,
- Hydrotherapy pool exercises,
- Ai Chi (water-based Tai Chi),
- Underwater treadmill therapy, aa) Graded motor imagery (GMI), bb) Mirror therapy to retrain brain-body connections, cc) Mindfulness-based stress reduction (MBSR) combining meditation and movement, dd) Balance exercises to improve stability, ee)Gaze stabilization techniques for dizziness and disorientation, ff) CBT.
- Pain score of ≥ 4 on Numerical Rating Scale (NRS-11) at Screening visit.
- Pain score of ≥ 4 on NRS-11 at Baseline visit averaged over 3 consecutive calendar days.
- Stated willingness and ability to comply with all study procedures.
- Has remained on the same psychiatric treatment regimen (e.g., medication, psychotherapy) for at least one (1) month prior to screening, and has stated willingness to remain on the same regimen for the duration of the study unless a change in treatment is recommended or agreed upon by the site investigator.
- For participants who could potentially become pregnant: negative urine pregnancy test at screening; agreement to either abstain from heterosexual intercourse or use an acceptable contraceptive method during study participation. Acceptable contraceptive methods include hormonal contraception, including oral contraceptive pills, tubal ligation, vasectomized partner, IUD or IUS (intrauterine device or system), or long-acting reversible contraceptives (LARC).
Who cannot join
- Any previous diagnosis of bipolar disorder or schizophrenia-spectrum disorder during the participant's lifetime, according to Diagnostic and Statistical Manual of Mental Disorders, version 5 (DSM-5-TR) criteria.
- New or existing diagnosis of moderate or severe alcohol or other substance use disorder in the past 6 months, according to DSM-5-TR criteria.
- New or existing diagnosis of obsessive-compulsive disorder and/or posttraumatic stress disorder in the past 30 days, according to DSM-5-TR criteria, and which is unstable in the clinical judgment of the investigator.
- New or existing primary diagnosis of anorexia nervosa, bulimia nervosa, or binge eating disorder in the past 3 months, according to DSM-5-TR criteria.
- Clinically significant neurodevelopmental, neurocognitive, or personality disorder, according to DSM-5-TR criteria.
- Moderate-High Risk of Suicide, according to the Columbia-Suicide Severity Rating Scale (C-SSRS) Screen Version - Recent (i.e., answers YES to Question 3 and NO to Question 6 (Moderate Risk), or YES to Question 4, 5, or 6 (High Risk)), or in the clinical judgement of the site investigator.
Show all 22Show fewer
- Lifetime history of a serious suicide attempt in the medical opinion of the site investigator.
- Changes in prescribed treatments for pain in the past 2 months that could confound study outcome assessments, in the opinion of the site investigator.
- Treatment with electroconvulsive therapy, transcranial magnetic stimulation, ketamine, or esketamine in the past 30 days.
- Currently diagnosed progressive neurological disease such as multiple sclerosis, chronic inflammatory demyelinating polyneuropathy, rapid progressive arachnoiditis, brain or spinal cord tumor, or severe/critical spinal stenosis (stenosis).
- Cancer-related pain.
- Diagnosis of malignancy other than basal cell carcinoma, or carcinoma in situ of the cervix within the past five years, to include life expectancy less than one year due to advanced malignancy.
- Autoimmune conditions that are known to cause pain.
- Inadequately managed general medical condition, in the opinion of the site investigator.
- Lifetime history of cerebral small vessel disease.
- Lifetime history of intracranial hemorrhage.
- Pregnant or breast feeding.
- MRI contraindication or electrically sensitive implants such as pacemakers, implanted cardioverter defibrillators, or neurostimulators. Routine dental hardware is not exclusionary.
- MRI intolerance.
- Previously enrolled in a DIADEM clinical trial. Note: a patient who screen fails is able to be rescreened at most one time.
- Has a history of a medical or psychiatric disorder, disease, condition, injury, symptoms, or circumstance that, in the opinion of the site investigator, may (1) reduce the participant's ability to fulfill the study requirements as per protocol; (2) adversely impact the integrity of the data or the validity of the study results; or (3) pose an increased risk to the participant during study participation.
- Participants with braids, dreadlocks, or other hairstyles that prevent access to the side of the head and who are unwilling to temporarily adjust their hairstyle to allow such access.
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
8 sites in 1 country
United States8 sites, 8 recruiting
- Recruiting
University of Michigan
Ann Arbor, Michigan, 48109
Katherine Scott, RN, BSN, 734-998-7022, jrsj@med.umich.edu
Daniel Clauw, MD
- Recruiting
Northwell Health - The Feinstein Institutes of Clinical Research
Manhasset, New York, 10030
Clinical Research Team, 516-253-7753, Neuroscienceresearch@northwell.edu
Ashesh Mehta, MD
- Recruiting
University of Minnesota Medical Center Fairview
Minneapolis, Minnesota, 55455
Eric Williamson, 612-626-6183, will0188@umn.edu
Alik Widge, MD, PhD
- Recruiting
WVU Rockefeller Neuroscience Institute
Morgantown, West Virginia, 26505
Tami Deal, CCRC, 304-293-0930, tldeal@hsc.wvu.edu
Manish Ranjan, MD
- Recruiting
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Maya Campbell, 646-596-3943, maya.campbell@mssm.edu
Bridget Mueller, MD, PhD
- Recruiting
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Sean McKenzie, 215-746-8041, sean.mckenzie@pennmedicine.upenn.edu
Quinn Tate, MD, MS
- Recruiting
University of Utah
Salt Lake City, Utah, 84108
Rachel Douglas, BS, CCRC, 801-587-2811, UltraSound_for_Fibromyalgia_Study@utah.edu
Rana Jawish, MD
- Recruiting
Washington University in St. Louis
St Louis, Missouri, 63110
Cristina Bowman, RN, 314-273-8257, bowmanc@wustl.edu
Simon Haroutounian, PhD, MSc.Pharm
About this study
Official title: Ultrasonic Neuromodulation of Cingulate Cortex for Fibromyalgia: A Blinded Randomized Sham-Controlled Trial
The goal of this clinical trial is to evaluate a new noninvasive brain stimulation intervention for fibromyalgia and to determine its effectiveness in reducing pain. Participants will receive four treatments over the course of one month and will complete surveys at multiple time points throughout the 16-week study.
- Conditions
- Fibromyalgia
- Being tested
- Focused Ultrasound
- Medical subject headings
- Fibromyalgia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Focused UltrasoundDevice
DIADEM device
| Study group | Role | What they receive |
|---|---|---|
| Focused Ultrasound | Active comparator | Not described Receives: Device: Focused Ultrasound |
| Sham Ultrasound | Sham comparator | Not described Receives: Device: Focused Ultrasound |
What is being measured
The primary outcome is the main question the study is designed to answer.
Numerical Rating Scale - 11 (NRS-11) pain score
The NRS-11 is a scale from 0-10 with higher values representing higher levels of pain.
Measured: 28 days following initial treatment
Secondary outcomes (7)
Fibromyalgia Impact Questionnaire Revised (FIQR)
The FIQR is a scale ranging from 0 to 100 that evaluates function, overall impact, and symptoms of fibromyalgia over the past 7 days. Higher scores represent more severe impact to the patient.
Measured: 28 days following initial treatment
Numerical Rating Scale - 11 (NRS-11) pain score response rate
≥ 30% reduction from baseline in NRS-11 score (the NRS-11 is a scale from 0-10 with higher values representing higher levels of pain).
Measured: 28 days following initial treatment
Patient-Reported Outcomes Measurement Information System (PROMIS-29) - Pain Interference Subscale
The PROMIS-29 is a 29 question survey assessing physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social roles and activities, pain interference, and pain intensity. The Pain Interference Subscale is scored on a 5 point scale and asks how much pain interfered with different activities (1 - Not at all; 2 - A little bit; 3 - Somewhat; 4 - Quite a bit; 5 - Very much). Scores are calculated as T-scores with a mean of 50 and a standard deviation of 10. Higher scores represent more pain interference.
Measured: 28 days following initial treatment
Numerical Rating Scale - 11 (NRS-11) pain score response rate
≥ 30% reduction from baseline in NRS-11 score (the NRS-11 is a scale from 0-10 with higher values representing higher levels of pain).
Measured: 7 days following initial treatment
Patient Global Impression of Improvement (PGI-I)
The PGI-I is a scale from 1-7 indicating how the patient has felt overall since beginning treatment. 1 - Very Much Improved; 2 - Much Improved; 3 - Minimally Improved; 4 - No Change; 5 - Minimally Worse; 6 - Much Worse; 7 - Very Much Worse.
Measured: 28 days following initial treatment
Patient Health Questionnaire-9 (PHQ-9)
The PHQ-9 is a 9-question survey asking "Over the last 2 weeks, how often have you been bothered by any of the following problems?" Each question is scored as:
0: Not at all;
- Several days;
- More than half the days;
- Nearly every day. The 9 scores are added together, and the total score ranges from 0 to 27, with higher numbers representing more bothersome problems.
Measured: 28 days following initial treatment
Numerical Rating Scale - 11 (NRS-11) pain score
The NRS-11 is a scale from 0-10 with higher values representing higher levels of pain.
Measured: 16 weeks following initial treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2025
- Study start11 Dec 2025
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for FibromyalgiaStudies of the same condition, open and under way.
- 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
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 180 participants (estimated)
Sponsor and investigators
- Lead sponsor
- SPIRE Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- University of Utah Data Coordinating Center
- Responsible party
- Sponsor
- Investigators
- Akiko Okifuji, PhD, Principal investigator, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07226648
- Sponsor's protocol ID
- SPIRE1002025
- Status last verified
- Aug 2026
- First submitted
- 7 Nov 2025
- Last updated
- 20 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided
Publications
Riis TS, Losser AJ, Kassavetis P, Moretti P, Kubanek J. Noninvasive modulation of essential tremor with focused ultrasonic waves. J Neural Eng. 2024 Feb 27;21(1). doi: 10.1088/1741-2552/ad27ef.
PubMed 38335553Riis TS, Feldman DA, Losser AJ, Okifuji A, Kubanek J. Noninvasive targeted modulation of pain circuits with focused ultrasonic waves. Pain. 2024 Dec 1;165(12):2829-2839. doi: 10.1097/j.pain.0000000000003322. Epub 2024 Jul 30.
PubMed 39073370Riis TS, Feldman DA, Kwon SS, Vonesh LC, Koppelmans V, Brown JR, Solzbacher D, Kubanek J, Mickey BJ. Noninvasive Modulation of the Subcallosal Cingulate and Depression With Focused Ultrasonic Waves. Biol Psychiatry. 2025 Apr 15;97(8):825-834. doi: 10.1016/j.biopsych.2024.09.029. Epub 2024 Oct 11.
PubMed 39396736
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ultrasonic Neuromodulation of Cingulate Cortex for Fibromyalgia: A Blinded Randomized Sham-Controlled Trial
- ClinicalTrials.gov ID
- NCT07226648
- Acronym / sponsor ID
- SPIRE1002025
- Conditions
- Fibromyalgia
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- SPIRE Therapeutics Inc.Industry (pharma, biotech, devices)
- Collaborators
- University of Utah Data Coordinating Center
- Study start
- 11 Dec 2025 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 10 Nov 2025 (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.
The goal of this clinical trial is to evaluate a new noninvasive brain stimulation intervention for fibromyalgia and to determine its effectiveness in reducing pain. Participants will receive four treatments over the course of one month and will complete surveys at multiple time points throughout the 16-week study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Focused Ultrasound | Active comparator | Device: Focused Ultrasound |
| Sham Ultrasound | Sham comparator | Device: Focused Ultrasound |
Who may qualify
- Ages
- 22 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (40 listed)
- Willing and able to provide informed consent.
- Age ≥ 22 years.
- Meets 2016 American College of Rheumatology criteria for fibromyalgia:
- Failure of at least two evidence-based medications or medications that are commonly used in clinical practice to treat fibromyalgia (e.g., pregabalin, duloxetine, milnacipran, sublingual cyclobenzaprine hydrochloride, tricyclics (e.g., amitriptyline, nortriptyline, desipramine),gabapentin, gabapentinoids, NSAIDS (including Cox-2 inhibitors), acetaminophen, SSRIs, SSNIs, muscle relaxants, non-sublingual forms of cyclobenzaprine hydrochloride, opioids, benzodiazepines), at least 1 of which is FDA-approved for the treatment of fibromyalgia (e.g., pregabalin, duloxetine, milnacipran, and sublingual cyclobenzaprine hydrochloride).
- Failure of one or more attempts at physical or Cognitive Behavioral Therapy (CBT) including:
Key exclusion criteria (22 listed)
- Any previous diagnosis of bipolar disorder or schizophrenia-spectrum disorder during the participant's lifetime, according to Diagnostic and Statistical Manual of Mental Disorders, version 5 (DSM-5-TR) criteria.
- New or existing diagnosis of moderate or severe alcohol or other substance use disorder in the past 6 months, according to DSM-5-TR criteria.
- New or existing diagnosis of obsessive-compulsive disorder and/or posttraumatic stress disorder in the past 30 days, according to DSM-5-TR criteria, and which is unstable in the clinical judgment of the investigator.
- New or existing primary diagnosis of anorexia nervosa, bulimia nervosa, or binge eating disorder in the past 3 months, according to DSM-5-TR criteria.
- Clinically significant neurodevelopmental, neurocognitive, or personality disorder, according to DSM-5-TR criteria.
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 UltrasoundDIADEM device | Device | Focused Ultrasound, Sham Ultrasound |
Primary outcome
Numerical Rating Scale - 11 (NRS-11) pain score
Time frame: 28 days following initial treatment
The NRS-11 is a scale from 0-10 with higher values representing higher levels of pain.
7 secondary outcomes
Fibromyalgia Impact Questionnaire Revised (FIQR)
Time frame: 28 days following initial treatment
Numerical Rating Scale - 11 (NRS-11) pain score response rate
Time frame: 28 days following initial treatment
Patient-Reported Outcomes Measurement Information System (PROMIS-29) - Pain Interference Subscale
Time frame: 28 days following initial treatment
Numerical Rating Scale - 11 (NRS-11) pain score response rate
Time frame: 7 days following initial treatment
Patient Global Impression of Improvement (PGI-I)
Time frame: 28 days following initial treatment
Patient Health Questionnaire-9 (PHQ-9)
Time frame: 28 days following initial treatment
Numerical Rating Scale - 11 (NRS-11) pain score
Time frame: 16 weeks following initial treatment
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 20 Aug 2026.
- Background: PubMed 38335553Riis TS, Losser AJ, Kassavetis P, Moretti P, Kubanek J. Noninvasive modulation of essential tremor with focused ultrasonic waves. J Neural Eng. 2024 Feb 27;21(1). doi: 10.1088/1741-2552/ad27ef.
- Background: PubMed 39073370Riis TS, Feldman DA, Losser AJ, Okifuji A, Kubanek J. Noninvasive targeted modulation of pain circuits with focused ultrasonic waves. Pain. 2024 Dec 1;165(12):2829-2839. doi: 10.1097/j.pain.0000000000003322. Epub 2024 Jul 30.
- Background: PubMed 39396736Riis TS, Feldman DA, Kwon SS, Vonesh LC, Koppelmans V, Brown JR, Solzbacher D, Kubanek J, Mickey BJ. Noninvasive Modulation of the Subcallosal Cingulate and Depression With Focused Ultrasonic Waves. Biol Psychiatry. 2025 Apr 15;97(8):825-834. doi: 10.1016/j.biopsych.2024.09.029. Epub 2024 Oct 11.
- Individual participant dataSharing planned: Undecided
Related trials for Fibromyalgia
Active, not recruiting
Objective Measurement of Pain Regulation in Individuals Who Have Received Internet-delivered Exposure-based Cognitive Behavior Therapy
Fibromyalgia
Enrolling by invitationPhase 3
Open-Label Safety Study of AXS-14 in Subjects With Fibromyalgia
Fibromyalgia
Recruiting
Exercise Interventions and Dietary Advice in Fibromyalgia and IBS
Fibromyalgia, Irritable Bowel Syndrome
Recruiting
Whole-body Cryotherapy in Those With Chronic Fatigue: A Feasibility Study
ME/CFS, Fibromyalgia (FM)
Recruiting
Auricular Acupuncture for Autonomic Balance and Pain in Fibromyalgia
Fibromyalgia Syndrome
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.
Akiko Okifuji, PhD principal investigator
University of Utah
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Focused Ultrasound in people with Fibromyalgia, run by SPIRE Therapeutics Inc. at 8 sites 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 40 inclusion and 22 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: looking for participants now, as of the sponsor's last update on 20 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites 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. Some participants in this study may receive a placebo. 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 Akiko Okifuji, PhD (801-585-7690, Akiko.Okifuji@hsc.utah.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Numerical Rating Scale - 11 (NRS-11) pain score (time frame: 28 days following initial treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07226648, which also lists 3 linked publications.
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 20 Aug 2026.