Impact of Switching from High- to Low-Sodium Oxybate on Ambulatory Blood Pressure in Patients with Narcolepsy

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EP: 1.Impact of Switching from High- to Low-Sodium Oxybate on Ambulatory Blood Pressure in Patients with Narcolepsy

EP: 2.Effectiveness and Safety of Low-Sodium Oxybate Dosages Greater Than 9 Grams in Study Participants With Narcolepsy

In this special report series from NeurologyLive, leading sleep medicine experts Eric Olson, MD, and Anita Shelgikar, MD—president-elect of the American Academy of Sleep Medicine—offer their perspectives on six late-breaking presentations from the 2025 SLEEP Annual Meeting in Seattle, Washington. With a focus on narcolepsy and hypersomnia, the panel provides timely insights into new and emerging data that could influence future clinical care.

Throughout the series, the discussion covers a range of pressing topics, from cardiovascular safety and high-dose efficacy of low-sodium oxybate to investigational therapies like TAK-861 and ALKS 2680. The panel also unpacks trends in prescribing behavior and the influence of social determinants of health, offering a comprehensive look at the evolving treatment landscape for central disorders of hypersomnolence.

This first episode covers new data from the open-label XYLO study, which evaluated the cardiovascular impact of switching narcoleptic patients from sodium oxybate to a lower-sodium formulation. The study showed a 4 mmHg reduction in mean 24-hour ambulatory systolic blood pressure, with exploratory endpoints trending similarly. In this segment, Olson and Shelgikar explore implications for long-term health, comorbid hypertension, and the need for extended follow-up. They also raise questions about medication confounders, like stimulant use, that could affect blood pressure readings, while also emphasize the broader need to consider cardiovascular risk in sleep disorder management.

Transcript edited for clarity.

Eric Olson, MD: This was a study Anita called the XYLO study, which was an open-label, single-arm study evaluating the switch from sodium oxybate to low-sodium oxybate in narcoleptic patients who had slightly elevated screening blood pressure—typically in the 130 to 155 mmHg range. The primary endpoint was a change in the 24-hour mean ambulatory systolic blood pressure from baseline on sodium oxybate to the end of treatment on low-sodium oxybate.

They also had some exploratory endpoints looking at systolic blood pressure at different time points, as well as diastolic blood pressure. They ended up enrolling 43 patients. The main finding was that the mean 24-hour systolic blood pressure dropped from 132 mmHg to 128 mmHg—a delta of 4 mmHg reduction. Their exploratory endpoints also trended toward lower blood pressure ranges as well, which was exciting.

So, the main conclusion was that transitioning patients with narcolepsy from sodium oxybate to low-sodium oxybate did appear to result in lower mean ambulatory systolic blood pressure over the 24-hour period, with the delta being 4 mmHg.

Anita Shelgikar, MD: Thanks for that summary, Eric. I agree with you—these are really interesting data. I think it really calls into question how we think about our patients and their sleep disorders in the context of their overall health and well-being. It's important to consider not only the primary sleep disorder, but also how our treatments may influence other aspects of health.

So, to see the data you summarized so nicely—about how sodium concentration may influence blood pressure readings during that six-week study period—I think it raises some really interesting questions. It also highlights the need for perhaps more sustained and longer-term follow-up. I'd love to hear your thoughts on that.

Eric Olson, MD: Yeah, I agree. Another question I had was: What percentage of patients were taking other stimulants, and to what extent did that influence outcomes? Maybe we would have seen even more dramatic results if that had been the only medication change during the study period.

It’s also unclear to me what percent of the patients were frankly hypertensive versus not. The results indicate that about a third of patients were on stable antihypertensives. It might have been interesting to see that data parsed out between those on antihypertensives and those not. But given that patients with narcolepsy seem to be at higher risk for hypertension and cardiovascular disease in general, I think these results are noteworthy.

Anita Shelgikar, MD: Yeah, I fully agree with you. I think there’s definitely more to come in this space.

REFERENCE
1. Somers V, Kovacs R, Alexander JK, et al. Impact of Switching from High- to Low-Sodium Oxybate on Ambulatory Blood Pressure in Patients with Narcolepsy. Presented at: 2025 SLEEP Annual Meeting; June 8-11; Seattle, WA. LBA1647