bluuebunny/crossref_metadata_2025 huggingface dataset:
0559 Solriamfetol Demonstrates Durable Cognitive Improvement in Adults with Obstructive Sleep Apnea and Excessive Daytime Sleepiness
Authors: Van Dongen Hans , Leary Eileen , Drake Christopher , Bogan Richard , Jaeger Judith , Rosenberg Russell , Streicher Caroline , Kwak Hannah , Bates Jay , Tabuteau Herriot
Published: May 2023

Introduction

Obstructive sleep apnea (OSA) is a common disorder characterized by repeated intermittent airway collapse—often a hypoxic event—resulting in disrupted sleep and excessive daytime sleepiness (EDS). Positive Airway Pressure (PAP) therapy reduces hypoxic events and mitigates sleep disruption, but EDS often persists. Cognitive impairment is a burdensome symptom in many patients with EDS associated with OSA, which leads to occupational and social dysfunction and degrades quality of life. Solriamfetol (Sunosi®) is approved to improve wakefulness in adults with EDS associated with OSA, but its effect on cognitive impairment was unknown. The SHARP study evaluated whether solriamfetol improves cognitive function in patients with OSA-associated EDS and impaired cognition, and the durability of cognitive effects across the day.

Methods

SHARP was a randomized, double-blind, placebo-controlled, crossover trial in 59 patients with OSA-associated EDS and concurrent cognitive impairment. All patients received solriamfetol (75mg for 3 days followed by 150mg/day) for 2 weeks, and placebo for 2 weeks, with treatment periods separated by a 1-week washout. The primary endpoint was change from baseline on the Coding subtest of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), which is equivalent to the Digit Symbol Substitution Test (DSST). Secondary endpoints measured durability of effect spanning an 8-hour period and Patient Global Impression of Severity (PGI-S).

Results

The study completion rate was 96.7%. Solriamfetol treatment improved performance on the DSST-RBANS compared to placebo (6.49 vs. 4.75, p=0.009), with an effect size (Cohen’s d) of 0.36. Solriamfetol also yielded improvements at post-dose timepoints throughout the day (solriamfetol-placebo difference): 2 hours (1.91, p=0.033), 4 hours (1.38, p=0.089; NS), 6 hours (2.33, p=0.004), 8 hours (1.58, p=0.022). Scores on the PGI-S improved with solriamfetol compared to placebo (-0.90 vs -0.61, p=0.034). The most common adverse events with solriamfetol treatment (incidence ≥3%) were nausea (6.9%) and anxiety (3.4%).

Conclusion

The adverse events profile and high completion rate suggest solriamfetol (150mg/day) was well tolerated. Moreover, solriamfetol improved cognition as measured by the DSST-RBANS, demonstrated durable effects over an 8-hour period, and reduced perceptions of symptom severity. Thus, in patients with OSA-associated EDS and impaired cognition, solriamfetol durably improved cognitive performance.

Support (if any)

Axsome Therapeutics Jazz Pharmaceuticals
0562 The characteristics of the older continuous positive airway pressure (CPAP) users in Japan: In comparison with the adult users
Authors: Kido Keisuke , Mihara Takenao , Wada Shin-ichi , Egawa Naohiro , Sugita Naoko , Hamano Toshiaki , Tachibana Naoko
Published: May 2023

Introduction

The characteristics of the older CPAP users have not been well studied, and accessibility to medical care and long-term follow up are the issues about their investigation of the older OSA patients. In this respect, Japan is in a unique position to look into reality of the situation, as virtually all the people have unlimited access to medical care and CPAP follow-up with one to three month interval is mandatory. Under this condition, the aim of this study is to reveal the characteristics of the older CPAP users compared to the adult users.

Methods

This is a retrospective study dealing with 340 obstructive sleep apnea patients who started CPAP therapy from May 2013 to Oct 2021 in our sleep laboratory. Two groups of CPAP users were extracted from these patients, older (n=44, with the age of 70 years or more, 75.8±4.4 years) and adult (n=26, with the age of 25-44 years old, 39.2±4.5 years) patients. We assessed the characteristics of demographic data, symptoms and comorbidity, diagnostic polysomnographic parameters, and CPAP adherence.

Results

The older CPAP users were leaner (BMI, older/adult, 24.9 [21.9-26.8]/31.3 [27.1-34.8], p< 0.0001) and less sleepy (Epworth Sleepiness Scale, older/adult, 8.0 [5.0-13.0]/15.5 [8.8-20.2], p< 0.0005). Apnea-hypopnea index (AHI) of two groups were not significantly different (older/adult, 38.6 [27.4-48.0]/49.5 [26.4-66.4]). Most of both older and adult patients continued to use CPAP more than one year (84.1 % and 92.3 %, respectively). CPAP adherence using more than one year in the older group was higher than that in the adult group (older/adult, 96.5 %/80.0 %).

Conclusion

Our study revealed that CPAP adherence in the older users was higher than that in the adult users, although the older CPAP users were leaner and less sleepy.

Support (if any)
0576 Characterization of Patients With Narcolepsy Treated vs Not Treated With Sodium Oxybate: A Propensity Score–Matched Cohort Study
Authors: Lipford Melissa , Asfahan Shahir , Singh Gajinder Pal , Moore J Layne , Tippmann-Peikert Maja , Kumar-M Praveen , Ip Wui , Awasthi Samir , Gudeman Jennifer , Krahn Lois
Published: May 2023

Introduction

Narcolepsy is a chronic sleep disorder with multiple comorbid conditions. Sodium oxybate (SXB) is strongly recommended for treatment of narcolepsy. This study used aggregate electronic health record (EHR) data to characterize demographic characteristics and comorbidities of patients with narcolepsy treated with or without SXB.

Methods

An EHR-based search identified first-time Mayo Clinic patients between 1975–2020. Patients had ≥1 narcolepsy-specific ICD-9/-10 code and ≥1 diagnostic mention of narcolepsy in clinical notes (natural-language-processing algorithm). Patients with narcolepsy treated with SXB were age/sex matched with a cohort without SXB treatment. Common comorbidities were identified using ICD-9/-10 codes and compared between cohorts (odds ratio [OR]).

Results

Of 4387 patients identified, 8% received SXB treatment (n=351; mean [IQR] age at first diagnosis code observed at Mayo Clinic, 32 [23.2-46.1] y; 65.5% female; 92.3% white); 4036 patients had no SXB treatment (mean [IQR] age at first diagnosis code observed at Mayo Clinic, 44.8 [29.8-59.0] y; 58.0% female; 88.9% white). The 10 most commonly reported comorbidities (overall population) were insomnia (46.6%), fatigue (46.3%), depression (42.2%), hypertension (36.2%), hyperlipidemia (34.2%), obstructive sleep apnea (32.3%), diabetes mellitus (31.3%), arrhythmia (27.3%), idiopathic hypersomnia (IH; 26.8%), and coronary artery disease (17.6%). A cohort of 351 patients without SXB were age/sex matched to patients with SXB for comparison of comorbidities. In the unadjusted analysis, P values were significant for differences between cohorts (OR [95% CI] SXB vs no SXB) for fatigue (0.72 [0.54-0.97]; P< 0.05; adjusted P>0.9) and IH (0.60 [0.43-0.84]; P< 0.01; adjusted P=0.29). After P value adjustment (Bonferroni correction), there were no significant differences between these cohorts in ORs for any comorbidity. The matched cohorts, which were younger than the overall population, had numerically lower rates of these diagnoses vs the overall population, except fatigue and IH in patients without SXB and depression in patients with SXB.

Conclusion

Among age-/gender-matched cohorts of patients with/ without SXB, there were no significant differences in comorbidities. Prevalence of comorbid IH/narcolepsy diagnoses highlight the diagnostic challenge in differentiating IH from narcolepsy type 2. SXB is highly effective but used by < 1:10 patients with narcolepsy in the Mayo Clinic health system.

Support (if any)

Avadel Pharmaceuticals
0577 Clinically Meaningful Improvements With Pitolisant in Adults With Narcolepsy: Pooled Analysis of Randomized Clinical Trials
Authors: Wells Audrey , Albers David , Doliba Markiyan , Zarycranski Donna , Schwartz Jean-Charles , Dayno Jeffrey
Published: May 2023

Introduction

Narcolepsy is characterized by symptoms indicative of sleep–wake dysregulation, notably excessive daytime sleepiness (EDS) and cataplexy. In 2021, the American Academy of Sleep Medicine (AASM) updated its clinical practice guidelines on the treatment of central disorders of hypersomnolence. The AASM identified clinical significance thresholds (CSTs) of a 2-point reduction in Epworth Sleepiness Scale (ESS) score and a 25% reduction in the frequency of cataplexy, amongst others, to compare posttreatment effects between intervention and placebo. This post hoc analysis evaluates the efficacy of pitolisant in the treatment of patients with narcolepsy using these updated CSTs.

Methods

Data were pooled from 2 randomized, placebo-controlled, 7- and 8-week studies (HARMONY-1, HARMONY-CTP) of pitolisant in adults with narcolepsy. Pitolisant was individually titrated over a 3-week period (maximum potential dose, 35.6 mg/day), and the dose remained stable thereafter. The analysis population for EDS included all patients who received pitolisant or placebo (ESS score ≥12 required for study inclusion). The analysis population for cataplexy included treated patients who experienced ≥3 attacks per week at baseline. The end-of-treatment value for the ESS was the score at the last study visit (last observation carried forward [LOCF]). The cataplexy endpoint was the weekly rate of cataplexy (WRC) during the stable dose period (LOCF).

Results

Data from 166 patients for EDS (pitolisant, n=85; placebo, n=81) and 122 patients for cataplexy (pitolisant, n=64; placebo, n=58) were analyzed. Mean (SD) baseline ESS score was 17.6 (3.0) in the pitolisant group and 17.9 (3.1) in the placebo group. Mean (SD) baseline WRC was 12.4 (10.7) and 9.9 (9.0), respectively. At the end of treatment, ESS score reduction of ≥2 points was observed in a significantly greater percentage of patients in the pitolisant group (72.9%) as compared with the placebo group (45.7%; P< 0.001). The percentage of patients with a reduction in WRC of ≥25% was significantly greater with pitolisant (78.1%) versus placebo (34.5%, P< 0.001).

Conclusion

Pitolisant provides statistically significant and clinically meaningful reductions in EDS and cataplexy in patients with narcolepsy, based upon the CSTs associated with the updated AASM clinical practice guidelines.

Support (if any)

Bioprojet Pharma and Harmony Biosciences, LLC.
0578 Clinician and Patient Global Impression in a Phase 2 Study of Mazindol (NLS-1021) in Adults with Narcolepsy Type 1 and Type 2
Authors: Bogan Richard , Stern Thomas , Corser Bruce , Franco Jennifer , Konofal Eric , Apostol George , Morse Anne , Kushida Clete , Thorpy Michael , Rosenberg Russell
Published: May 2023

Introduction

Mazindol is the first partial orexin 2 receptor agonist and triple monoamine reuptake inhibitor in development for the treatment of narcolepsy. Clinician and Patient Global Impression (CGI and PGI, respectively) for cataplexy and excessive daytime sleepiness were assessed as secondary endpoints in the phase 2 (POLARIS, NLS-1021) multicenter study of mazindol ER in adult participants with narcolepsy type 1 (NT1) or type 2 (NT2) (ClinicalTrials.gov Identifier: NCT04923594).

Methods

Adults diagnosed with NT1 or NT2 who were washed out of narcolepsy medications at baseline were included into the study. Patients were treated with mazindol ER (NLS-2) at once-daily 2 mg for one week and once-daily 3 mg thereafter or matching placebo (PBO) on a 1:1 ratio. Throughout the study, CGI Severity (CGI-S) and PGI Severity (PGI-S) for cataplexy severity and excessive daytime sleepiness, respectively, were assessed and compared with scores at baseline. Both scales have five levels of severity: “None”, “Mild”, “Moderate”, “Severe”, or “Very Severe.”

Results

Sixty-seven participants were randomized (NT1 33.3% in NLS-2 group; 35.3% in PBO). At baseline, the mean CGI-S – Cataplexy was approximately 3.7 and CGI-S – Sleepiness approximately 3.4. Despite the small sample size, at the end of the double-blind (DB) period, the NLS-2 group demonstrated clinically and statistically significant improvements vs. PBO in both CGI-S – Sleepiness (d = –0.7, p = 0.016) and CGI-S – Cataplexy (d = –0.8, p = 0.020). At baseline, the mean PGI-S – Cataplexy was approximately 3.2 and PGI-S – Sleepiness approximately 3.7. At the end of the DB period, the NLS-2 group demonstrated clinically and statistically significant improvements vs. PBO in both PGI-S – Sleepiness (d = –0.8, p = 0.007) and PGI-S – Cataplexy (d = –0.8, p = 0.023).

Conclusion

Mazindol ER resulted in significant improvements of cataplexy severity and sleepiness in both conditions as rated by both clinicians and participants. These secondary outcome results support the efficacy of mazindol ER on cataplexy attacks, in NT1 participants, and on sleepiness, in NT1 as well as in NT2 participants.

Support (if any)

NLS Pharmaceutics
0586 An observational retrospective study of the prevalence of comorbid postural orthostatic tachycardia syndrome (POTS) in narcolepsy
Authors: Meskill Gerard , Rege Riddhi , Meskill Sarah
Published: May 2023

Introduction

Postural orthostatic tachycardia syndrome (POTS) is a clinical syndrome of dysautonomia associated with an excessive increase in heart rate following a shift to standing posture. As of 2019, POTS has a prevalence of 1-3 million (0.3-0.9%) in the United States. Narcolepsy is a chronic neurologic condition of persistent hypersomnolence irrespective of total sleep time that also is associated with REM-sleep dissociative features (i.e., cataplexy, sleep paralysis, sleep-related hallucinations). In recent years, viral infections have been established as a trigger for both neurologic conditions.

Methods

A manual chart review was performed for records from 11/1/2020 to 12/20/2022. The overall clinic population of narcolepsy was identified by searching the electronic medical record for the ICD-10 codes G47.411 (narcolepsy type 1 [NT1]), and G47.419 (narcolepsy type 2 [NT2]). The past medical history of these charts then was searched for a history of POTS to identify patients with both conditions. A separate chart review was performed to identify all patients with POTS in the clinic.

Results

Of the 1,433 total patients in the clinic population, 207 narcolepsy patients (NT1=73, 35.3%; NT2=134, 64.7%) and 24 POTS patients were identified. The co-morbid prevalence of narcolepsy with POTS was 8.7% (18, 95% CI 5.2-13.4%); of those patients with POTS, 75% had narcolepsy (95% CI 53.3-90.2%). Co-morbid prevalence was higher in NT1 (13, 17.8% with 95% CI 9.8-28.5%) than NT2 (5, 3.7% with 95% CI 1.2-8.5%). The overall co-morbid prevalence and the NT1 co-morbid prevalence was significantly higher than the overall clinic POTS population (1.26% with 95% CI 0.75-1.98%) and the general population.

Conclusion

The prevalence of POTS is significantly higher in narcolepsy patients than the overall general population, especially in the NT1 subgroup. Clinicians should consider screening POTS patients for narcolepsy, and vice versa. Further studies are warranted to explore the etiology of co-morbid narcolepsy and POTS.

Support (if any)

N/A
0588 DNS and Sleep-Dependent Memory Consolidation in Pediatric Narcolepsy Type 1
Authors: Maski Kiran , Boduch Madeline , Heckler Gillian , Worhach Jennifer , Scammell Thomas , Behn Cecilia Diniz , Mylonas Dimitrios , Stickgold Robert
Published: May 2023

Introduction

Disrupted nighttime sleep (DNS) is common in narcolepsy type 1 (NT1), yet its impact on cognitive function is unknown. Given known associations between sleep-dependent memory consolidation and N2 sleep spindles, we hypothesized that NT1 impairs memory consolidation, due to fragmented N2 sleep and altered N2 sleep spindles in the NT1 group.

Methods

In this case-control study, we trained n=23 NT1 participants [mean age 15.8 years (3.2)] and n=28 healthy control (HC) patients [13.6 years (3.7)] to criterion on a spatial declarative memory task before a nocturnal in-lab polysomnogram and then gave them a cued recall test upon awakening in the morning. NT1 participants could take SSRI/SNRI medication for cataplexy but were weaned off wake-promoting medications and excluded if on an oxybate. We extracted wake and sleep stage bout numbers from sleep and N2 spindle characteristics from the polysomnogram and conducted linear regression with memory consolidation results across groups.

Results

Adjusting for age, NT1 participants had longer sleep duration than HC, more N1%, lower N3%, higher Wake/N1 Index, as well as more bouts per hour of Wake, N1, N2, REM than controls (p’s < 0.04). Compared to HC, NT1 subjects had similar N2 spindle density, amplitude, and sigma power, but shorter duration of N2 spindles (p=0.009). More NT1 participants could not meet performance criterion on the initial learning task and required an easier memory task vs. HC (p=0.02) despite being older than HC. NT1 participants showed a trend for impaired memory consolidation vs. HC across a night of sleep after adjusting for age, gender, and total sleep time (p=0.07). Across groups, shorter N2 spindle duration (p=0.02) but not increased N2 bout number was associated with worse sleep-dependent memory consolidation.

Conclusion

Compared to controls, NT1 participants showed encoding difficulties but only a trend difference in memory consolidation despite greater sleep fragmentation. NT1 participants had briefer N2 sleep spindles and overall, these shorter N2 spindles were associated with greater memory consolidation deficits. Future sleep therapeutic studies are needed to determine if sleep-dependent memory consolidation can be improved to address daytime cognitive problems in NT1 patients.

Support (if any)

Jazz Pharmaceuticals and National Institutes of Health grant 5K23NS104267-2
0590 Effect of a whole-food plant-based diet on daytime sleepiness in patients with obstructive sleep apnea
Authors: Cheung Joseph , Patel Kripa , Lawson Melanie
Published: May 2023

Introduction

Consumption of diet rich in high saturated fats has been associated with a higher degree of daytime sleepiness. A whole-food, plant-based (WFPB) dietary pattern, which is low in saturated fat, has been shown to be beneficial in weight loss and other health conditions. Patients with obstructive sleep apnea (OSA) frequently experience excessive daytime sleepiness despite treatment. This study aims to assess the effect of a short term (21 days) WFPB diet on daytime sleepiness in patients with obstructive sleep apnea.

Methods

Patients were recruited from the Mayo Clinic Jacksonville sleep clinic who have a diagnosis of OSA who are on PAP therapy but have daytime sleepiness with Epworth Sleepiness Scale (ESS) score of 5 or above. Participants were asked to follow a strict WFPB diet for 21 days using the Fork Over Knives handbook as a guide. They were also asked to complete ESS before switching to and after completing a WFPB diet for 21 days.

Results

A total of 10 participants completed the 21-day WFPB diet. Eight out of ten participants had reported a reduction in daytime sleepiness. Overall, we found a mean decrease in ESS score of 3.8 in all participants, with 3 patients had a significant decrease in ESS score of ≥ 7. All participants completed the study with ≥ 90% adherence to a WFPB diet. In addition, participants also reported a mean weight loss of 4.2 kg. Two participants noted headaches during this 21-day period.

Conclusion

Significant improvement with daytime sleepiness was found in patients who switched to a WFPB diet for 21 days. No significant correlation between improvement in ESS and weight loss was found.

Support (if any)
0592 Efficacy of Lower-Sodium Oxybate by Baseline Sleep Inertia in a Phase 3 Clinical Study in Patients With Idiopathic Hypersomnia
Authors: Dauvilliers Yves , Chen Abby , Whalen Marisa , Macfadden Wayne , Thorpy Michael
Published: May 2023

Introduction

Idiopathic hypersomnia is a debilitating neurologic sleep disorder. Sleep inertia (difficulty awakening) is a common symptom that can significantly impair functioning and quality of life. This post hoc analysis evaluated response to lower-sodium oxybate (LXB; Xywav®) by baseline sleep inertia in a phase 3 trial (NCT03533114).

Methods

Eligible participants began LXB treatment with an open-label treatment titration and optimization period (10–14 weeks), followed by a 2-week stable-dose period (SDP). Participants were randomized to placebo or continued LXB treatment during a 2-week, double-blind, randomized withdrawal period (DBRWP). Using the visual analog scale for sleep inertia (VAS-SI), participants rated their difficulty awakening during baseline, SDP, and DBRWP on a 100-mm line with anchors at 0 (very easy) and 100 (very difficult). VAS-SI terciles comprised score segments of < 44 (group A), ≥44 to < 70 (group B), and ≥70 (group C). Efficacy assessments included the Epworth Sleepiness Scale (ESS), Idiopathic Hypersomnia Severity Scale (IHSS), Clinical Global Impression of Severity (CGIs), and Patient Global Impression of Change (PGIc).

Results

Participants (A, n=34; B, n=33; C, n=32) were a mean (SD) 40.7 (13.5) years of age and primarily female (74%). At baseline, participants with the highest VAS-SI scores had numerically higher mean (SD) ESS (A=16.0 [3.1], B=15.6 [2.6], C=17.1 [2.4]) and IHSS (A=26.7 [7.7], B=34.5 [5.9], C=36.3 [5.5]) scores. Participants with the highest baseline sleep inertia were more frequently rated severely ill on the CGIs (A=17.6%, B=12.1%, C=34.4%). Baseline total sleep time trended higher with increasing VAS-SI scores. From baseline to end of SDP, mean (SD) scores decreased (improved) on the ESS (A=−9.9 [5.1], B=−9.8 [3.5], C=−10.0 [5.1]) and IHSS (A=−14.1 [9.9], B=−19.0 [9.0], C=−18.1 [9.9]), regardless of baseline sleep inertia; nearly all (99%) participants reported improvement on the PGIc. Mean (SD) VAS-SI scores decreased by 9.3 (11.9), 31.5 (14.8), and 42.8 (22.9) in groups A, B, and C, respectively, at end of SDP. Spearman correlation coefficients for VAS-SI and IHSS items assessing sleep inertia were moderate (≥0.3) to strong (≥0.6).

Conclusion

Participants with higher baseline sleep inertia generally had greater baseline disease burden. LXB treatment was efficacious across subgroups regardless of baseline sleep inertia.

Support (if any)

Jazz Pharmaceuticals.
0604 Diagnostic Delay and Its Causes in Narcolepsy Type 1 in Japan : with special emphasis on cataplexy
Authors: Tachibana Naoko , Mihara Takenao , Sugita Naoko , Egawa Naohiro , Hamano Toshiaki
Published: May 2023

Introduction

Although narcolepsy type 1 is characterized by the pathognomonic symptom of cataplexy, it has been reported that there is long diagnostic delay in various countries. However, the causes of this delay have not been studied enough except for European counties. Japan is in a unique position in that all the people have public medical insurance coverage that allows them to have unlimited direct access to any medical specialists, therefore, once the patients experienced cataplexy, theoretically they could consult their symptom to sleep specialists with no financial burden. Under this condition, this study aims at characterizing the diagnostic delay and its causes in patients with narcolepsy type 1, and investigating whether cataplexy contributes to the accelerating the diagnostic process.

Methods

This retrospective study dealt with consecutive 45 patients (20 men/ 25 women) with narcolepsy type 1, whose diagnosis was made from April 2006 to September 2022 based on the PSG/MSLT criteria of the International Classification of Sleep Disorders, 3rd edition. We performed the chart review to retrieve demographic and clinical information, and the diagnostic process including the stage before coming to our sleep clinic.

Results

The diagnostic delay was 13.7±11.9 years (range 0.5-47 years, median 9.0 years). Cataplexy was the first manifestation in 9 out of 45 (20.0%), and excessive daytime sleepiness (EDS) and cataplexy occurred almost at the same time in 11(24.4%) patients. 24 (53.3%) patients considered cataplexy disturbing and/or of pathological nature, but for the remaining 21 patients, cataplexy was a kind of habit until EDS became problematic for their daily life. Seven (15.6%) patients had been diagnosed as having epilepsy, and the first medical contact of 4 patients was emergency room visit due to cataplexy leading to the diagnoses of hyperventilation syndrome, transient ischemic attack, and consciousness loss attack of unknown origin.

Conclusion

There was substantial diagnostic delay in patients with narcolepsy type 1, and cataplexy did not seem to be properly evaluated in Japan.

Support (if any)
0605 Effect of a Mindfulness-Based Intervention on Hypersomnia Symptom Severity in Participants with Narcolepsy: A Preliminary Report
Authors: Schuiling Matthew , Ong Jason , Zee Phyllis , Hakenjos Alec , Victorson David , Fox Rina , Rogers Ann , Mundt Jennifer
Published: May 2023

Introduction

Narcolepsy is a chronic sleep disorder that can greatly inhibit sleep quality, daytime functioning, and health-related quality of life. Although medication is the first-line treatment to manage narcolepsy symptoms, behavioral interventions may provide additional benefits. We examined the impact of varying lengths of a group mindfulness-based intervention on symptoms of hypersomnia among participants diagnosed with narcolepsy.

Methods

We randomized 60 participants to 3 versions of a mindfulness-based intervention: brief (4 weeks), standard (8 weeks), or extended (12 weeks). Groups of four participants met weekly or biweekly with a trained instructor via videoconference. Participants completed the Hypersomnia Severity Index (HSI) at baseline, 4 weeks, 8 weeks, and 12 weeks to assess hypersomnolence severity and related impairment. Paired samples t-tests were conducted to examine differences from baseline to post-treatment for the HSI total score, symptoms subfactor, and impairment subfactor. Linear mixed models (LMM) were conducted on the HSI total score to examine changes in the three groups across each assessment time point. Analyses were conducted using an intent-to-treat approach with the last observation carried forward for participants who had missing data after the baseline assessment (brief, n = 1; standard, n = 5; extended, n = 3).

Results

There were no significant group differences on the HSI total score or subfactor scores at baseline. Analyses revealed a significant decrease in HSI total scores from baseline to post-treatment (d=.533, p<.001), a significant decrease in hypersomnia symptoms (d=.373, p<.01) and a significant decrease in hypersomnia impairment (d=.549, p<.001). LMM revealed a main effect over time, indicating that hypersomnia severity improved from baseline to the study endpoint, across all treatment arms (t=-3.58, p<.001) but no significant time x treatment interaction effects emerged.

Conclusion

This preliminary report suggest that mindfulness programs can reduce hypersomnia symptoms for individuals with narcolepsy over a 12-week period, regardless of the duration of treatment. Additional analyses are being examined to determine ideal treatment duration to maximize benefits and minimize costs.

Support (if any)

This research was supported by a grant from NCCIH (R34AT009551)
0608 PAX8/PAX8-AS1 DNA methylation levels are not associated with sleep duration in medicated patients with unexplained hypersomnolence
Authors: Madrid Andy , Papale Ligia , Cook Jesse , Tran Kieulinh , Prairie Michael , Vascan Ana Maria , Alisch Reid , Plante David
Published: May 2023

Introduction

The biological basis of daytime sleepiness and excessive sleep duration in patients with unexplained hypersomnolence is unknown. However, a growing body of evidence suggests modulations in the epigenome coincide with objective measures of sleep, suggesting epigenetic mechanisms may be related to hypersomnolence. Previously, we identified significant correlations between saliva DNA methylation abundance at nine CpG sites located in the PAX8/PAX8-AS1 genes and total sleep time measured using polysomnography in unmedicated, clinical patients with unexplained hypersomnolence. Since psychotropic medications frequently affect clinical sleep testing and may also affect DNA methylation, here we attempted to replicate prior findings in a separate, medicated sample.

Methods

Forty-three medicated clinical patients with unexplained hypersomnolence were drawn from a larger study of a multimodal sleep assessment that included ad libitum overnight polysomnography. Pyrosequencing quantified DNA methylation at the previously identified CpG sites in PAX8/PAX8-AS1. Multivariate linear models, adjusting for age, sex, and body mass index (BMI), assessed relationships between total sleep time and DNA methylation at these prespecified CpG sites.

Results

Participants were young -to middle-aged (Mean Age = 32.2±10 years) and predominantly female (Percent Female = 95.3%), with a mean BMI of 27.8±5.4kg/m2. Epworth Sleepiness Scale (ESS) score was consistent with complaints of daytime sleepiness (Mean ESS =15.1±-4.3). Total sleep time on ad libitum polysomnography was 9.2±1.7 hours (range 5.6-12.8 hours). No significant associations between DNA methylation at the PAX8/PAX8-AS1 CpG sites and sleep duration were identified in adjusted models.

Conclusion

We were unable to replicate findings of an association between sleep duration and DNA methylation levels at specific PAX8/PAX8-AS1 CpG sites in medicated patients with unexplained hypersomnolence. Further research to clarify whether this is a result of medications affecting the DNA methylation levels at these CpG sites or previously identified associations between DNA methylation of PAX8/PAX8-AS1 and sleep length are spurious will require replication of prior findings in a novel unmedicated cohort and quantification of within-subjects effects of psychotropic medications on DNA methylation levels in genes of interest.

Support (if any)

AASM Foundation (229 SR-20 - Diversity Supplement Grant)
0609 Samelisant, Histamine 3 Receptor Agonist for the Potential Treatment of Excessive Daytime Sleepiness in Patients with Narcolepsy
Authors: Nirogi Ramakrishna , Ravula Jyothsna , Jayarajan Pradeep , Goyal Vinod Kumar , Jetta Satish , Shinde Anil , Benade Vijay
Published: May 2023

Introduction

Samelisant (SUVN-G3031) is a potent and selective histamine 3 receptor inverse agonist. In orexin knockout mice, samelisant produced wake-promoting and anticataplectic effects suggesting its potential therapeutic utility in the treatment of narcolepsy. Safety and tolerability studies in animals and healthy human volunteers suggested a favorable risk/benefit profile for samelisant.

Methods

Samelisant is currently being evaluated in a double blind, Phase-2 proof of concept study in USA and Canada for narcolepsy with or without cataplexy (ClinicalTrials.gov Identifier: NCT04072380). The study is recruiting subjects diagnosed with narcolepsy as per ICSD-3 criteria, aged between 18 to 65 years with an Epworth Sleepiness Scale (ESS) score of ≥12 and mean Maintenance of Wakefulness Test (MWT) time of < 12 min. A total of 171 subjects are expected to be randomized into 3 treatment arms (placebo, samelisant 2 mg and samelisant 4 mg) in 1:1:1 ratio. Each subject will receive either placebo or study drug once daily for 2 weeks. The primary efficacy endpoint is change in MWT score from baseline to week 2. Key secondary endpoint is change in ESS from baseline to week 2. Safety will be monitored throughout the study by medical monitor and by data safety monitoring committee. As the study is still recruiting, demographics and baseline characteristic data for the currently enrolled subjects is summarized descriptively. Since the study is blinded, a breakdown of baseline characteristics by treatment group will not be available until after completion.

Results

At the data cutoff date of Nov 30, 2022, a total of 155 subjects were randomized in the study. The median age of subjects was 30 years (range: 18-57 years) with mean BMI of 28.5 kg/m2 (range: 18.3- 43.9 kg/m2). Overall, 57% subjects were of narcolepsy type-1, 71% were female and 71% were Caucasian. Mean (SD) baseline values of MWT and ESS scores were 6.1 (4.4) and 17.2 (2.8), respectively.

Conclusion

Baseline characteristics are consistent with the general narcolepsy population. The study is currently enrolling subjects with narcolepsy and the data readout is expected in Q2 2023.

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0610 The effects of wakefulness promoting agents on neuronal activity in nucleus accumbens
Authors: MacLean Jennifer , Nataraj Jaya , Mousavi S A Seyyed , Galion Anjalee , Sanger Terence
Published: May 2023

Introduction

Both modafinil and methylphenidate are frequently utilized for maintenance of wakefulness in narcolepsy and other sleep disorders. Both have been demonstrated to affect dopamine transporter, leading to an increase extracellular dopamine. Subsequent functional connectivity changes between nucleus accumbens and pallidum are noted. Animal studies demonstrate changes in neuronal activity with methylphenidate in nucleus accumbens. To our knowledge there has been no direct examination of human neural activity in nucleus accumbens after administration of modafinil or methylphenidate, compared to baseline.

Methods

Two subjects with placement of stereotactic electroencephalographic (sEEG) electrodes to identify optimal location for permanent deep brain stimulation electrodes in nucleus accumbens were given wakefulness promoting agents to optimize testing of stimulation sites during inpatient hospitalization. Assessment occurred at least 48 hours following surgical electrode insertion under inhaled general anesthesia. Retrospective analysis was performed on neural activity in nucleus accumbens during rest on and off medication. Frequency content was calculated in the following bands: delta (1-3 Hz), theta (4-7 Hz), alpha (8-12 Hz), beta (13-30 Hz), gamma (30-50 Hz), and high gamma (70-100 Hz). Power in each band is reported as the percentage contribution of each band to summed power across all bands.

Results

Total power was noted to be lower with both modafinil and methylphenidate. With modafinil, the beta band ratio was decreased (22.3% vs. 30.5%), the gamma band ratio was increased (24% vs. 22.4%), and the high gamma band was increased (39.5% vs. 32.9%). With methylphenidate, only the high gamma band was increased (40.3% vs. 22.9%).

Conclusion

Both methylphenidate and modafinil increase high gamma band neural activity in nucleus accumbens, while modafinil has additional effects on beta and gamma bands. Further assessment of modafinil and methylphenidate’s effects on neural activity are indicated to help better understand their mechanism of action and appropriate use as wakefulness promoting agents.

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0611 Treatment Satisfaction and Preferences in People With Narcolepsy Transitioning From Sodium Oxybate to Lower-Sodium Oxybate
Authors: Bae Charles , Zee Phyllis , Leary Eileen , Macfadden Wayne , Fuller Douglas , Candler Shawn , Husain Aatif
Published: May 2023

Introduction

Lower-sodium oxybate (LXB; Xywav®), which contains the same active moiety as higher-sodium oxybate (SXB; Xyrem®) but with 92% less sodium, is approved by the US Food and Drug Administration (FDA) for treating cataplexy or excessive daytime sleepiness in patients ≥7 years of age with narcolepsy. LXB is recognized as clinically superior to SXB in narcolepsy by the US FDA due to lower chronic sodium exposure; however, real-world data describing patient preferences and satisfaction are lacking.

Methods

Transition Experience of persons with Narcolepsy taking Oxybate in the Real-world (TENOR; NCT04803786) was a patient-centric, prospective, observational, noninterventional, virtual-format study of US adults with narcolepsy (type 1 or 2) transitioning from SXB to LXB within the previous/upcoming 7 days. Longitudinal data collected during transition and for 21 weeks thereafter included responses to the Ease of Switching Medications Scale (EOSMS), Forced Preference Questionnaire (FPQ), and Treatment Satisfaction Questionnaire for Medication-version II (TSQM-vII).

Results

The mean (standard deviation [SD]) age of the 85 participants (narcolepsy type 1, n=45; narcolepsy type 2, n=40) was 40.3 (13.0) years; most were female (73%) and White (87%). Mean (SD) time on current SXB regimen was 57.8 (52.1) months. Nearly all participants took SXB (82/85, 96%) twice nightly prior to transition and LXB (82/84, 98%) twice nightly after transition. Most participants (61/73, 84%) reported that switching from SXB to LXB was “extremely easy, not difficult at all” or “easy” on the EOSMS, and most (59/73, 81%) preferred LXB to SXB on the FPQ. Among participants who preferred LXB, lower sodium content (56/59, 95%) and fewer cardiovascular issues (27/59, 46%) were cited as the most common reasons. There were minimal mean (SD) changes in TSQM-vII scores for global satisfaction (1.1 [18.6]), satisfaction with effectiveness (1.0 [16.8]), side effects (4.1 [23.7]), or convenience (−3.9 [15.2]) after transitioning from SXB to LXB.

Conclusion

Overall, most participants indicated that switching from SXB to LXB was “easy” or “extremely easy.” Most participants preferred LXB to SXB, primarily because of its lower sodium content. Satisfaction with oxybate treatment was maintained following transition to LXB.

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Jazz Pharmaceuticals
0613 Actigraphy-Based Sleep Disruption and Diurnal Biomarkers of Autonomic Function in Paroxysmal Atrial Fibrillation
Authors: Khazaie Sepideh , Wang Lu , Araujo Matheus , Chung Mina , Heinzinger Catherine , Van Wagoner David , Mehra Reena
Published: May 2023

Introduction

Sleep architectural disruption is associated with atrial fibrillation (AF), however, associated autonomic influences remain unclear and it is unknown if this detriment persists during wakefulness. We hypothesize diurnal-patterned associations of sleep disruption and autonomic dysfunction in patients with paroxysmal AF

Methods

We analyzed data from the Sleep Apnea and Atrial Fibrillation Biomarkers and Electrophysiologic Atrial Triggers (SAFEBEAT) study designed to examine paroxysmal AF and sleep apnea involving simultaneous collection of continuous electrocardiogram monitoring (Heartrak Telemetry®) and actigraphy (Actiwatch GTX) for 7-21 days. Heart rate variability (HRV) measures in frequency and time domains were used as surrogates of autonomic function and averaged per sleep/wake per day. A linear mixed-effects model assuming compound symmetry correlation structure was used to assess the relationship of HRV with actigraphy-derived sleep data.

Results

The analytic sample (age 60.1±12 years, body mass index 32.6±6.7 kg/m², 36% female, 75% White) included 108 participants with paroxysmal AF. Significant associations were observed between sleep indices and HRV measures during wakefulness: a) Sleep latency with high-frequency power (HFP), b) total sleep time, wakefulness after sleep onset (WASO) and number of awakenings with low-frequency power (LFP), and c) Sleep efficiency with standard deviation of normal R-R intervals (SDNN) and coefficient of variation (CV). During sleep, a) total sleep time was associated with LFP/HFP ratio (LHR), and b) number of awakenings with LHR. Significant sleep-wake interactions were observed between a) Sleep latency and HFP, b) Sleep efficiency with SDNN and CV, c) WASO with SDNN, CV, and LFP, and d) number of awakenings with CV and LFP.

Conclusion

Our novel findings indicate actigraphy-based measures of sleep disruption were associated with autonomic function alterations and these relationships exhibited diurnal variability in patients with paroxysmal AF. Results provide unique insights into differential relationships of immediate (during sleep) versus sustained (during wakefulness) autonomic dysfunction related to sleep disruption which may contribute to atrial arrhythmogenesis

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0623 Effects of bright light therapy on objective and subjective sleep in patients with non-seasonal depression and eveningness
Authors: Chan Joey , Feng Hang Liang , Zhang Jihui , Chan Ngan Yin , Li Tim Man Ho , Chau Steven Wai Ho , Liu Yaping , Li Shirley Xin , Wing Yun Kwok
Published: May 2023

Introduction

This study reported the effect of bright light therapy with gradual advanced timing on the sleep parametersin patients with major depressive disorder (MDD) and eveningness.

Methods

A total of 93 adults were randomized to receive either 10,000 lux bright light therapy (BLT group) or 50lux dim red light therapy (placebo group) for a total of 5 weeks. Timings of both treatments were initiated at their habitual wake time and was advanced gradually each week. Sleep diary data were collected weekly. Actigraphic data were collected at the baseline and during the last week of the 5-week treatment. Sleep parameters including time in bed (TIB), sleep onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST) and sleep efficiency (SE) were extracted. Concordance of the sleep diary and actigraphy sleep parameters were assessed by Pearson’s correlation with p-value adjusted for multiple comparisons. The changes of sleep parameters between the two groups were assessed by linear mixed model.

Results

Significant correlations between sleep diary and actigraphy were found for WASO (r=0.35, p = 0.01) and TST (r=0.40, p=0.01), but no correlation was found for TIB, SOL and SE. A greater advance in the diary-based light-out time (group*time p=0.03, 15 vs 32min) and rise time (group*time p=0.04, 38 vs 53min) was found in the BLT group compared to placebo group, while dairy-based WASO, TST and SE comparably improved with time in both groups. However, there were no significant difference between the two groups in all of the actigraphic parameters after treatment.

Conclusion

Five-week of either type of light therapy with gradual advance in timing improved subjective WASO, TST and SE, while BLT led to a greater advance in the light-out time and rise time when compared to the placebo group. These changes were not captured by the actigraphic measurements. The discrepancies between subjective and objective sleep parameters suggested the need to consider incorporating multiple measures when assessing sleep in patients with depression and eveningness.

Support (if any)

This project was supported by the Health and Medical Research Fund, The Government of Hong Kong SAR (Ref 12131131).
0626 Type of screen time and the relationship between anxiety, depressive and insomnia symptoms in college students
Authors: Brombach Ruth , Dietch Jessica , Sy John , Trevorrow Tracy , Zhou Eric
Published: May 2023

Introduction

Limited and conflicting evidence examines associations between screen time, depression, anxiety and insomnia in adolescents. Surprisingly few studies focus on college students who face unique sleep-related challenges, frequent media use and elevated rates of mental health problems. Therefore, the goal of the present study was to examine the influence of different types of screen time on the relationship between anxiety/depressive symptoms and insomnia symptoms in college students.

Methods

Participants (N = 1,085 college students with a mean age of M = 21.15 [SD = 5.51]) completed questionnaires of demographics, anxiety, depression, insomnia, and daily screen time. Type of screen time was classified as: (1) social, (2) non-social, or (3) productivity. We conducted correlations and used Model 1 of the PROCESS macro version 3.5 was used to determine whether type of screen time moderated the relationship between depressive or anxiety symptoms and insomnia.

Results

Insomnia symptoms were moderately correlated with anxiety (r = .49, p = <.001) and depressive symptoms (r = .60, p = <.001). Anxiety symptoms were correlated with social screen time (r = .09, p = <.01); depressive symptoms were correlated with non-social screen time (r = .13, p = <.001). Social screen time moderated the relationship between anxiety symptoms and insomnia symptoms (b = -.03, SE = .01, p = .01) and the relationship between depressive symptoms and insomnia symptoms (b = -.02, SE = .01, p = .02). Productivity and non-social screen time were not significant moderators.

Conclusion

Anxiety symptoms were only correlated with social screen time whereas depressive symptoms were only correlated with using non-social screen time. Moderation analyses revealed social screen time moderated the relationship between anxiety/depressive symptoms and insomnia symptoms. Elevated social screen time was associated with elevated insomnia symptoms among participants with less anxiety/depressive symptoms. Distinguishing between non-social and social screen time may be relevant when examining the influence of screen time on depressive/anxiety symptoms and their relationship with insomnia symptoms. Further research could address these findings in a clinical sample and examine whether intervening on specific types of screen time impacts the relationship between depression/anxiety and insomnia.

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None
0628 Retinal responsivity increases after light therapy and is associated with improved depression: Preliminary findings from a RCT
Authors: Wescott Delainey , Klevens Alison , Franzen Peter , Siegle Greg , Roecklein Kathryn , Rohan Kelly
Published: May 2023

Introduction

Light therapy is a first line treatment for seasonal depression but is not effective for everyone. Understanding mechanisms of light therapy may help predict who will successfully respond to treatment. Individual differences in the retina’s responsivity to light may underlie differences in treatment response given prior work linking reduced retinal responsivity in seasonal depression. This study tested if retinal responsivity changed across a light therapy intervention and whether changes in retinal responsivity were associated with improved depression.

Methods

Participants diagnosed with Major Depressive Disorder, With Seasonal Pattern were randomized to 6 weeks of light therapy or cognitive behavioral therapy for seasonal affective disorder (CBT-SAD). Participants in the light therapy group (N=52) were on average 41.9 years (SD=14.8) and predominantly women (72%). Retinal responsivity was assessed using the post-illumination pupil response (PIPR), measured mid-day in winter pre- and post-treatment. The net PIPR (red minus blue) was calculated as a percent of baseline 10-30 seconds post stimulus. Depression severity was measured using the Structured Interview Guide for the Hamilton Depression Rating Scale – Seasonal Affective Disorder version (SIGH-SAD). Using multilevel models, we tested 1) if the PIPR changed from pre- to post-treatment and 2) if changes in the PIPR predicted improvements in depression. All analyses included a random intercept of participant ID and controlled for age, gender, time of testing, and the pupillary light reflex (PLR).

Results

There was a significant main effect of time on the PIPR, such that PIPR increased from pre- to post-light treatment (b=0.29; SE=0.13; p=0.03). There was a significant negative association between changes in PIPR and changes in depression, such that increases in PIPR were associated with decreases in depression symptom severity (b= -0.18; SE=0.06; p=0.01).

Conclusion

Retinal responsivity increased across a light therapy intervention and increases in retinal responsivity were associated with improved depression. It is possible an upregulation in retinal responsivity drives antidepressant effects of light therapy, either through direct or circadian pathways. However, changes in retinal responsivity measured throughout treatment are required to discern whether these changes are mechanistic.

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