Quell TENS Device to be Used in NMOSD Study

The use of Quell technology will be implemented in an upcoming study conducted by NeuroMetrix to determine the effectiveness of the device’s transcutaneous electrical nerve stimulation (TENS) in treating patients with Neuromyelitis Optica Spectrum disorder (NMOSD). Having previously been evaluated for relief in other forms of neuropathic pain, the study will provide additional research into whether TENS is an appropriate method for pain relief in patients with NMOSD.¹

A modified Quell device, compatible with Bluetooth low energy technology, will pair with mobile applications during the study, creating an alternative electrode placement and stimulation pattern. A National Institutes of Health-funded study of the use of TENS for fibromyalgia has employed the same method.

“We are pleased to support Dr. [Michael] Levy and his colleagues in this clinical trial. NMOSD is a disabling disease without safe and effective treatment options,” Shai N. Gozani, MD, PhD, president and CEO, NeuroMetrix, said in a statement.1 “This rigorous randomized controlled trial will add to the growing body of clinical data on the utility of Quell technology in chronic pain conditions with a neuropathic pain component. There are significant unmet clinical needs in the treatment of neuropathic pain that Quell may be able to eventually address.” 

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The randomized control trial (RCT) will include 46 patients with NMOSD, with participants designated to active or sham Quell devices. Patients will be fitted and trained to use the TENS devices at home and self-administer for a 1-hour period each day. Following treatment over a period of 4 weeks, patients will then move to an open-label phase for another 4 consecutive weeks. Pain will be scored on the numerical rating score (NRS), assessing changes in pain intensity at the completion of the experimental phase, 4 weeks from the baseline.  

Previously, the Quell TENS device has been assessed for its ability to provide pain freedom from knee pain and chronic pain, as well as to evaluate its impact on sleep in patients with chronic pain. In a real-world study presented at the 11th Biennial Congress of the European Pain Federation (EFIC), September 4-7, 2019, in Valencia, Spain, those who had sleep impairment related to chronic pain experienced improved sleep (increased Total Sleep Time and sleep efficiency) and a reduction in pain intensity and pain interference with sleep during a period of fixed site-TENS device use.²

The need for more treatment options, including symptomatic therapies, for patients with NMOSD is critical, though a small number have been added to the clinical toolbox in recent years. As well, a better understanding of the underlying pathology and biology of the disease is of utmost importance. Additional research, published earlier this year in Multiple Sclerosis Journal, explored age of onset (AO) of NMOSD and its correlation with vision loss, concluding that patients with an AO of under 21 years of age were more likely to have severe residual vision loss (SRVL), as well as blindness (P = .004), binocular optic neuritis (ON; P = .009), and recurrent optic neuritis when compared to patients with an AO greater than or equal to 21 years. The odds of SRVL were 4.68 times greater in patients with an AO less than 21 years (95% CI, 1.53-14.34; P = .007) after adjusting for race, sex, and disease disruption.³

Other treatments have been recently explored in the care of this patient population, namely eculizumab and inebilizumab, 2 of the aforementioned recently approved agents for NMOSD. Research presented at the Muscular Dystrophy Association’s 2021 Clinical and Scientific Conference in March 2021 concluded that eculizumab (Soliris; Alexion) demonstrated safety and showed no increase in infection rates among patients with NMOSD or generalized myasthenia gravis (gMG). In PREVENT and its OLE, 137 patients with NMOSD were exposed to eculizumab and 47 patients were exposed to placebo for 276.6 PY and 51.5 PY, respectively. The serious infection rate was 9.4, 10.4, and 15.5 across eculizumab (PREVENT), eculizumab in the OLE, and placebo groups, respectively.⁴

Results from another RCT and OLE for inebilizumab, published in Annals of Neurology, showed patients with NMOSD experience similar rates of being attack-free, extending as far as 4 years, and suggesting an enduring effect of the treatment. In total, 216 of the 230 participants initially randomized and dosed opted to enter the OLE where they received inebilizumab 300 mg every 28 weeks for at least 2 years. In both the RCT and the OLE, 87.7% of patients receiving inebilizumab remained attack-free; however, those in the OLE remained attack-free for up to 4 years.⁵

REFERENCES
1. NeuroMetrix reports that Quell® technology is to be evaluated for Neuromyelitis Optica Spectrum Disorder (NMOSD) in a randomized control trial. News release. BioSpace. June 15, 2021. Accessed July 1, 2021. https://www.biospace.com/article/releases/neurometrix-reports-that-quell-technology-is-to-be-evaluated-for-neuromyelitis-optica-spectrum-disorder-nmosd-in-a-randomized-controlled-trial/
2. Gozani S, Chester D, Madhaven T, Kong X. Improved sleep in individuals using transcutaneous electrical nerve stimulation for chronic pain management. Presented at: 11th Biennial Congress of the EFIC; September 4-7, 2019; Valencia, Spain. P012.
3. Macaron G, Khoury J, Bena J, et al. Early age of onset predicts severity of visual impairment in patients with neuromyelitis optica spectrum disorder. Mult Scler J. Published online January 6, 2021. doi: 10.1177/1352458520981736
4.. Alexion receives FDA approval of Soliris® (eculizumab) for the treatment of adults with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody positive. News release. Alexion Pharmaceuticals. Published June 27, 2019. Accessed March 22, 2021. https://news.alexion.com/press-release/product-news/alexion-receives-fda-approval-soliris-eculizumab-treatment-adults-neuromy
5. Aktas O, Smith MA, Rees WA, et al. Serum glial fibrillary acidic protein: a neuromyelitis optica spectrum disorder biomarker. Ann Neurol. 2021;89(5):895-910. doi:10.1002/ana.26067