Key Points
- SPIRE’s DIADEM device uses focused ultrasound neuromodulation to stimulate the areas of the brain affected by chronic pain and depression.
- The company recently published clinical trial results that have added further evidence for using DIADEM in patients with these conditions.
Chronic pain and depression research studies led by Brian J. Mickey, MD, PhD, Jan Kubanek, PhD, Akiko Okifuji, PhD, and their colleagues at the University of Utah have recently been published.
These clinical trial results have allowed SPIRE, a focused ultrasound neuromodulation company, to continue building clinical evidence to support the safety and efficacy of its DIADEM device.
Chronic Pain
This pilot study (NCT05674903) enrolled 20 participants with generalized chronic pain. Several baseline and post-treatment measures of chronic pain, depression, and anxiety were used to analyze efficacy. MRI registration allowed the team to locate the anterior cingulate cortex (ACC) as the treatment target. With a double-blind, randomized control study design, the DIADEM device was then used to administer noninvasive, deep brain, low-intensify focused ultrasound (LIFU) to one cohort while another group of participants received the sham treatment. The treatment and sham sessions each lasted 40 minutes. When receiving active stimulations, the average participant pain reduced by 60.0% immediately following treatment, and the average pain levels remained 43.0% lower than baseline on day 1 and 33.0% on day 7. A total of 55% and 30% of subjects reported a reduction greater than 50% on day 1 and day 7, respectively. The stimulation was well tolerated with temporary, mild side effects and no adverse events. In the sham group, 15% of the participants experienced a clinically meaningful reduction of pain on day 1, and 20% of the sham group had reduced pain on day 7. The authors concluded that the direct LIFU stimulation of the ACC led to “rapid, clinically meaningful, and durable improvements in pain severity.”
Dr. Kubanek commented, “The rapid onset of the pain symptom improvements, as well as their sustained nature, are intriguing and open doors for applying these noninvasive treatments to the many patients who are resistant to current treatments.”
See “Noninvasive targeted modulation of pain circuits with focused ultrasonic waves,” in Pain. (Open Source)
Depression
In this randomized, double-blind, sham-controlled pilot clinical trial (NCT05301036), 22 participants with treatment-resistant depression were enrolled for LIFU targeting the subcallosal cingulate (SCC). Forty minutes of bilateral ultrasonic stimulation was delivered to the SCC outside the MRI after participants underwent functional MRI (fMRI) to quantify target engagement. Mood state was measured before and after treatment while depression severity was measured before treatment, 24 hours after treatment, and 7 days after treatment. The stimulation was well tolerated. Target-specific fMRI changes in SCC activity during stimulation were measured in 16 participants. Additionally, the fMRI blood oxygenation level–dependent (BOLD) group analysis showed a statistically significant decrease in fMRI BOLD activity at the target area, suggesting inhibition of this brain region due to ultrasound stimulation. Significant improvements were measured in the mood and depression scores for the treatment group, leading the authors to conclude that ultrasonic stimulation could modulate SCC activity and rapidly reduce depressive symptoms.
“In the depression clinical trial, a single, 40-minute stimulation session produced immediate improvements in symptoms,” said Dr. Riis. The framework for pivotal trials for both indications is now being established.
See “Noninvasive modulation of subcallosal cingulate and depression with focused ultrasonic waves” in Biological Psychiatry.
The Company and its Technology
SPIRE’s long-term goal is obtaining regulatory approval for these and other indications, as current treatments for mood disorders, anxiety disorders, and addiction are often ineffective. The research team is seeking to create new options with specific, precise neuromodulation of circuits deep in the brain.
As a spin out from the University of Utah Department of Biomedical Engineering, SPIRE’s DIADEM neuromodulation device delivers LIFU to selectively and controllably modulate the deep brain circuits involved in these disorders. The DIADEM device directly measures and compensates for the attenuation of ultrasound by the human head and hair, which has been the key barrier for transcranial ultrasound. See the April 2024 company profile.
See the University of Utah Press Release about the Chronic Pain Study and media coverage in SciTech Daily: One Treatment, Lasting Relief: Groundbreaking Ultrasound Device Successfully Treats Chronic Pain in Clinical Trials
See media coverage in Psychology Today: Can Sound Waves Treat Depression?