Ultrasound stimulation of the cingulate cortex to reduce fibromyalgia pain

Ultrasonic Neuromodulation of Cingulate Cortex for Fibromyalgia: A Blinded Randomized Sham-Controlled Trial

This tests a noninvasive focused ultrasound treatment to try to reduce pain in adults with fibromyalgia who have not improved with medications and therapy.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 180 (estimated)
• Ages: 22 Years and up
• Sex: All
• Sponsor: SPIRE Therapeutics Inc. (industry)
• Locations: 4 sites (Minneapolis, Minnesota and 3 other locations)
• Trial ID: NCT07226648 on ClinicalTrials.gov

What this trial studies

This interventional program delivers focused ultrasound to the cingulate cortex, a brain region involved in pain processing, as a noninvasive neuromodulation approach for fibromyalgia. Participants receive four treatment sessions over the course of one month and complete symptom and safety surveys at multiple time points across a 16-week follow-up. Eligible adults must meet the 2016 American College of Rheumatology criteria for fibromyalgia and have previously failed at least two evidence-based medications and one or more attempts at exercise- or CBT-based therapies. The trial is sponsored by SPIRE Therapeutics with data coordination support and is being conducted at three academic medical centers in the United States.

Who should consider this trial

Good fit: Ideal candidates are adults aged 22 or older who meet the 2016 ACR criteria for fibromyalgia and who have failed at least two standard medications and at least one attempt at physical or CBT-based therapies.

Not a fit: Patients whose symptoms respond well to current treatments, who do not meet the diagnostic criteria, or who cannot undergo focused ultrasound are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, this could offer a noninvasive treatment option that reduces chronic pain and improves daily function for people with fibromyalgia who have not responded to standard therapies.

How similar studies have performed: Other noninvasive neuromodulation methods, such as transcranial magnetic stimulation, have shown mixed results in fibromyalgia, while focused ultrasound targeting the cingulate cortex is a newer, less-tested approach.

Eligibility criteria

Inclusion Criteria:

1. Willing and able to provide informed consent.
2. Age ≥ 22 years.
3. Meets 2016 American College of Rheumatology criteria for fibromyalgia:

   1. Generalized pain, defined as pain in at least 4 of 5 regions, is present, AND
   2. Widespread pain index (WPI) ≥ 7 and symptom severity scale score (SSS) ≥ 5, or WPI of 4-6 and SSS score ≥ 9, AND
   3. Symptoms have been present at a similar level for at least 3 months, AND
   4. A diagnosis of fibromyalgia is valid irrespective of other diagnoses. A diagnosis of fibromyalgia does not exclude the presence of other clinically important illnesses.
4. Failure of at least two evidence-based medications (i.e., pregabalin, duloxetine, milnacipran) for the treatment of fibromyalgia.
5. Failure of one or more attempts at physical or Cognitive Behavioral Therapy (CBT) including:

   1. Aerobic exercise like walking, cycling, and swimming,
   2. Water therapy/hydrotherapy with warm water exercises,
   3. Tai Chi involving slow, controlled movements,
   4. Yoga,
   5. Resistance training,
   6. Bodyweight exercises,
   7. Pilates,
   8. Myofascial release therapy applying gentle pressure on trigger points,
   9. Massage therapy,
   10. Trigger point therapy targeting specific pain points,
   11. Joint mobilization,
   12. Postural retraining to correct body alignment,
   13. Balance and coordination exercises,
   14. Feldenkrais method for movement awareness,
   15. Alexander technique to enhance posture and movement efficiency,
   16. Transcutaneous Electrical Nerve Stimulation (TENS) for pain relief,
   17. Heat therapy using hot packs, infrared, or paraffin wax,
   18. Cold therapy with ice packs or cryotherapy,
   19. Ultrasound therapy for deep tissue relaxation,
   20. Biofeedback to control muscle tension and pain response,
   21. Gentle static stretching for prolonged duration,
   22. Active dynamic stretching for full range of motion,
   23. Proprioceptive Neuromuscular Facilitation (PNF) stretching,
   24. Hydrotherapy pool exercises,
   25. Ai Chi (water-based Tai Chi),
   26. 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.
6. Pain score of ≥ 4 on Numerical Rating Scale (NRS-11) at Screening visit.
7. Pain score of ≥ 4 on NRS-11 at Baseline visit averaged over 3 consecutive calendar days.
8. Stated willingness and ability to comply with all study procedures.
9. 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.
10. For participants who could potentially become pregnant: negative urine pregnancy test at screening; agreement to use a highly effective method of contraception (≤ 1% pregnancy rate) including tubal ligation, vasectomized partner, IUD or IUS (intrauterine device or system), or long-acting contraceptives (LARC).

Exclusion Criteria:

1. 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.
2. 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.
3. 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.
4. 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.
5. Clinically significant neurodevelopmental, neurocognitive, or personality disorder, according to DSM-5-TR criteria.
6. 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.
7. Lifetime history of a serious suicide attempt in the medical opinion of the site investigator.
8. Changes in treatment for pain in the past 2 months.
9. Treatment with electroconvulsive therapy, transcranial magnetic stimulation, ketamine, or esketamine in the past 30 days.
10. 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).
11. Cancer-related pain.
12. 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.
13. Autoimmune-related pain.
14. Inadequately managed general medical condition, in the opinion of the site investigator.
15. Lifetime history of cerebral small vessel disease.
16. Lifetime history of intracranial hemorrhage.
17. Pregnant or breast feeding.
18. Implanted medical device in the head or neck.
19. MRI contraindication or intolerance.
20. Previously enrolled in a DIADEM clinical trial. Note: a patient who screen fails is able to be rescreened at most one time.
21. Has a history of any 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.
22. 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.

Where this trial is running

Minneapolis, Minnesota and 3 other locations

• University of Minnesota Medical Center Fairview — Minneapolis, Minnesota, United States (RECRUITING)
• Northwell Health - The Feinstein Institutes of Clinical Research — Manhasset, New York, United States (RECRUITING)
• University of Utah — Salt Lake City, Utah, United States (RECRUITING)
• WVU Rockefeller Neuroscience Institute — Morgantown, West Virginia, United States (RECRUITING)

Study contacts

• Principal investigator: Akiko Okifuji, PhD — University of Utah
• Study coordinator: Akiko Okifuji, PhD

Conditions: Fibromyalgia