RELIEV-CM Pilot Study Data Further Supports ShiraTronics’ Neuromodulation Device to Treat Chronic Migraine

ShiraTronics announced new 12-month data from its RELIEV-CM pilot study, with results showing that treatment with the company’s neuromodulation device led to sustained reductions in migraine frequency and improvement in quality of life among patients with chronic migraine (CM). The company remains active in enrolling participants for its RELIEV-CM2 pivotal trial, a larger, double-blind study further testing the device’s therapeutic potential.¹

In this prospective, multicenter study, patients underwent a 28-day screening period to then received the investigational neuromodulation device, which comprised bilateral, subcutaneous implantation of pulse generators and leads targeting the ON and SON nerve pathways. Over a 12-month follow-up, results revealed a 9.6 average reduction in monthly headache days and a 9.6 average reduction in monthly migraine days (MMDs) relative to baseline. Above all, the neuromodulation device was considered safe, with no unanticipated adverse events (AEs) reported.

In the data update, ShiraTronics noted that patients on the investigational device had sustained improvements in migraine-specific quality of life measures across multiple domains, as well as saw reductions in rescue medication use and headache severity. When culminating the new 12-month findings, the data further builds on previously reported 12-week data, where patients experienced a mean 11.3-day reduction in monthly headache days.

"The long-term results from this pilot study are particularly encouraging and reinforce the potential of this therapy to deliver meaningful, sustained relief for people living with chronic migraine," Samer Narouze, MD, PhD, division chief of pain medicine at University Hospitals, and Brian Grosberg, MD, PhD, director of the Hartford Healthcare Headache Center in Connecticut, said in a statement.¹

READ MORE: Patient-Reported Study Identifies Common Symptoms and Timing During Migraine Prodrome

The study investigators added, "As National Co-Principal Investigators of the RELIEV-CM2 study, we're optimistic about what this investigational neuromodulation system could represent for patients who have exhausted conventional treatment options. These findings offer real hope for a population that has long needed better solutions."

The ShiraTronics system differs than other approved or investigational products by being an implantable and dual-target device with continuous stimulation. Mechanistically, it is closer to classic occipital/peripheral nerve stimulation approaches than to the trigeminal-only, vagus, remote electrical nerve, or single-pulse transcranial magnetic stimulation (sTMS).

Previously reported data showed that responder rates, considered a 50% reduction in MHD or MMD, were 56% at 4 weeks and 100% at 12 weeks for both MHD and MMD. Additional data showed significant reductions in headache severity at week 4 and 12, with improvements seen in secondary outcomes such as MSQ and Migraine Disability Assessment scores. At the 12-week mark, investigators recorded reductions of 14.4 and 13.5 days/month in monthly headache days and MMDs, respectively.²

The ongoing RELIV-CM2 trial, launched in December 2024, looks to build on RELIEV-CM. RELIEV-CM2 includes patients aged 22 years and older who’ve had migraine for at least 12 months, experienced at least 15 or more MHDs, and have episodes lasting more than 4 hours. Patients with any previous history of treatment with a neurostimulator or who’ve received onabotulinumtoxinA injections for purposes other than managing migraine, are excluded from the study.³

REFERENCES
1. ShiraTronics Announces Positive 12-Month Follow-Up Results from RELIEV-CM Pilot Study, Demonstrating Sustained Clinical Benefit with Investigational Implantable Neuromodulation Therapy for Chronic Migraine. News release. ShiraTronics. September 16, 2025. https://www.prnewswire.com/news-releases/shiratronics-announces-positive-12-month-follow-up-results-from-reliev-cm-pilot-study-demonstrating-sustained-clinical-benefit-with-investigational-implantable-neuromodulation-therapy-for-chronic-migraine-302555416.html
2. Grosberg B, Goadsby PJ, Green M, et al. A prospective study assessing initial safety and performance of an implantable novel migraine therapy system in RELIEVing, interrupting, and preventing chronic migraine (RELIEV-CM). Presented at: American Headache Society conference.
3. ShiraTronics Initiates IDE Pivotal Study of Implantable Neuromodulation Therapy for Chronic Migraine. News release. ShiraTronics. December 3, 2024. Accessed September 17, 2025. https://www.prnewswire.com/news-releases/shiratronics-initiates-ide-pivotal-study-of-implantable-neuromodulation-therapy-for-chronic-migraine-302320417.html