For Doctors in a Hurry
- Researchers investigated if proximal hypoglossal nerve stimulation effectively treats moderate-to-severe obstructive sleep apnea in patients intolerant to positive airway pressure.
- This randomized controlled trial at 23 centers evaluated 104 adults with a mean apnea-hypopnea index of 35.7 events per hour.
- At month seven, 58.2% of treated patients achieved the primary endpoint compared to 13.5% of the control group.
- The researchers concluded that proximal nerve stimulation provides clinically significant responses and represents a viable therapeutic option for obstructive sleep apnea.
- Clinicians may consider this multicontact stimulation approach for patients who cannot tolerate standard positive airway pressure therapy.
Obstructive sleep apnea remains a significant clinical challenge, affecting nearly one billion people globally and contributing to a high burden of cardiovascular and neurocognitive morbidity [1, 2]. While continuous positive airway pressure (CPAP) is the established first-line therapy, long-term adherence is often poor, leaving many patients with untreated moderate-to-severe disease [3, 4]. Hypoglossal nerve stimulation has emerged as a validated rescue therapy for these patients, offering significant improvements in sleep architecture and daytime sleepiness [5, 6]. However, traditional systems often require complex electrode placement and the surgical integration of respiratory sensors to synchronize stimulation with breathing [7, 8]. A recent randomized controlled trial now evaluates a streamlined approach using proximal hypoglossal nerve stimulation to address these technical hurdles, targeting the main trunk of the nerve to simplify surgical implantation [9].
Trial Design and Patient Characteristics
The study was a 7-month randomized controlled trial followed by a 6-month open-label extension conducted at 23 U.S. health centers (ClinicalTrials.gov identifier NCT04950894). The trial enrolled 104 adults aged 22 years or older with a diagnosis of moderate-to-severe obstructive sleep apnea. In a departure from traditional trial designs where only the intervention arm undergoes a procedure, all 104 participants underwent surgical implantation with the proximal hypoglossal nerve stimulation system at baseline. This approach allowed for a controlled comparison of the stimulation therapy itself while ensuring all participants eventually received the active intervention. Following the surgical procedure, participants were randomly assigned in a 2:1 ratio to either the treatment group (n = 67) or the control group (n = 37). To measure the specific effect of the neurostimulation, therapy was initiated at month 1 for the treatment group, while the control group remained implanted but inactive until month 7. The study population had a mean age of 55.6 years (SD, 9.0) and a mean body mass index of 30.6 kg/m2 (SD, 3.0), representing a cohort typically encountered in sleep medicine clinics who may struggle with conventional airway management. Baseline assessments confirmed a high disease burden among the participants prior to the start of therapy. The mean preimplantation apnea-hypopnea index (AHI) was 35.7 events/h (SD, 12.8), reflecting significant respiratory instability. Furthermore, the mean preimplantation oxygen desaturation index (ODI), a metric that measures the hourly frequency of blood oxygen level drops, was 36.7 events/h (SD, 13.4). These metrics established a clear physiological baseline to evaluate the efficacy of proximal nerve stimulation in reducing nocturnal respiratory events and improving systemic oxygenation, which is critical for mitigating the cardiovascular risks associated with untreated sleep apnea.
Primary Efficacy and Symptom Reduction
The primary efficacy of proximal hypoglossal nerve stimulation was evaluated using a composite end point defined as the proportion of patients achieving a greater than 50% improvement from baseline in the apnea-hypopnea index (AHI) and an absolute AHI below 20 events/h at month 7. This metric ensures that responders experience both a substantial relative reduction in respiratory events and a transition to a lower clinical severity tier, which directly correlates with reduced cardiovascular strain. At the 7-month assessment, 58.2% (95% CI, 45.5% to 70.2%) of the treatment group achieved this primary end point, whereas only 13.5% (95% CI, 4.5% to 28.8%) of the control group met the same criteria. These data indicate that the active neurostimulation therapy, rather than the surgical procedure itself, drove the observed improvements in airway patency. Secondary outcomes focused on physiological markers of nocturnal hypoxia and subjective patient experiences. The researchers tracked the oxygen desaturation index (ODI), a measure of the frequency of blood oxygen level drops per hour of sleep, defining a clinical response as a reduction of at least 25% from baseline. The study found that ODI was reduced by at least 25% in 68.7% (95% CI, 56.2% to 79.4%) of the treatment group, compared to 37.8% (95% CI, 22.5% to 55.2%) of the control group. This stabilization of oxygen levels is a critical clinical target for reducing the long-term cardiovascular risks associated with intermittent hypoxemia in obstructive sleep apnea. Patient-reported outcomes, specifically daytime sleepiness, were assessed using the Epworth Sleepiness Scale (ESS), a validated questionnaire where higher scores indicate greater daytime somnolence. In the treatment group, the median ESS score improved from 10.0 (IQR, 7.0 to 14.0) at baseline to 6.0 (IQR, 5.0 to 9.0) at month 7, reflecting a move into the subclinical range for sleepiness. In contrast, the median ESS score in the control group remained at 9.0 (baseline IQR, 7.0 to 11.0; month 7 IQR, 6.0 to 11.0). These results suggest that the reduction in nocturnal respiratory events translated into a tangible improvement in daytime function and alertness, offering a meaningful quality-of-life benefit for patients receiving active proximal nerve stimulation.
Safety and Technical Considerations
This study evaluated a specific iteration of neurostimulation technology designed to overcome the anatomical challenges of earlier devices. Unlike traditional distal stimulation, which targets the nerve branches closer to the tongue base and requires meticulous dissection, this approach utilizes multicontact stimulation of the proximal portions of the hypoglossal nerve. This technical configuration is designed to simplify the surgical procedure by allowing for easier electrode implantation, potentially reducing operative complexity and time in the operating room for the surgeon. Safety data from the trial were favorable, as the researchers reported that no serious procedure-related adverse events occurred during the study period among the 104 implanted participants. Despite the observed improvements in respiratory metrics and daytime somnolence, the researchers identified several constraints that influence the clinical application of these findings. The study was limited by a lack of blinding, a relatively small sample size of 104 patients, and a short follow-up period of seven months for the primary controlled phase. These factors necessitate further long-term data to confirm the durability of the response and the safety profile over several years before this can be widely adopted as a standard alternative to continuous positive airway pressure. This clinical trial was funded by LivaNova PLC, the developer of the proximal neurostimulation system used in the study.
References
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3. Kim DH, Kim SW, Han JS, et al. Comparative effectiveness of hypoglossal nerve stimulation and alternative treatments for obstructive sleep apnea: a systematic review and meta-analysis.. Journal of sleep research. 2024. doi:10.1111/jsr.14017
4. Kent D, Stanley J, Aurora RN, et al. Referral of adults with obstructive sleep apnea for surgical consultation: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment.. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2021. doi:10.5664/jcsm.9594
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6. Kim DH, Kim SW, Han JS, Kim G, Basurrah MA, Hwang SH. Hypoglossal Nerve Stimulation Effects on Obstructive Sleep Apnea Over Time: A Systematic Review and Meta-analysis.. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2024. doi:10.1002/ohn.617
7. Wollny M, Heiser C, Sommer U, Schöbel C, Braun M. Adverse Events with Hypoglossal Nerve Stimulation in the Treatment of Obstructive Sleep Apnea-A Systematic Review of Clinical Trials and Real-World Data.. Journal of clinical medicine. 2024. doi:10.3390/jcm13154282
8. Costantino A, Rinaldi V, Moffa A, et al. Hypoglossal nerve stimulation long-term clinical outcomes: a systematic review and meta-analysis.. Sleep & breathing = Schlaf & Atmung. 2020. doi:10.1007/s11325-019-01923-2
9. Malhotra A, Schwartz AR, Lovett E, et al. Proximal Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea in the OSPREY Study : A Randomized Controlled Trial.. Annals of internal medicine. 2026. doi:10.7326/ANNALS-25-04414
