bluuebunny/crossref_metadata_2025_split huggingface dataset:
0346 Cannabinol (CBN) effects in insomnia disorder: A randomised, double-blind, placebo-controlled, crossover, clinical trial protocol
Authors: Lavender Isobel , McGregor Iain , Sureav Anastasia , McCartney Danielle , Irwin Chris , Marshall Nathaniel , Gordon Chris , D'Rozario Angela , Saini Bandana , Grunstein Ron , Yee Brendon , Hoyos Camilla 
Published: May 2023

Abstract

Introduction
There is a clear need for novel interventions for insomnia disorder. Growing evidence suggests a role of the endogenous cannabinoid system in regulating circadian sleep-wake cycles, highlighting a potential avenue for novel therapeutics. Cannabinol (CBN), a trace cannabinoid formed through oxidation of delta-9-tetrahydrocannbinol (THC), is hypothesised to impact sleep. Despite anecdotal and ­preclinical evidence, the effects of CBN isolate on sleep have never examined through well-designed clinical trial procedures.

Methods
This randomised, double-blind, placebo-controlled, three-arm, crossover, single-site, pilot study will investigate the acute effects of oral dose CBN at 30 and 300 mg in twenty patients with clinician-diagnosed insomnia disorder (and Insomnia Severity Index [ISI] Score ≥15). Across three treatment sessions, each separated by two-weeks washout, participants will receive two doses of CBN and matched placebo, at random. Participants will undergo overnight sleep assessment using in-laboratory polysomnography and next-day neurobehavioral function tests. The primary outcomes are CBN (30 and 300 mg) effects on sleep continuity (wake after sleep onset minutes), compared to placebo, measured using polysomnography.

Results
Secondary outcomes include changes to sleep micro-architecture, traditional sleep staging, and absolute spectral power during non-rapid eye movement sleep. Various other subjective and objective safety measures will be obtained.

Conclusion
This study will provide novel preliminary data on the effects of CBN on sleep and next-day function in adults living with insomnia disorder which will inform the design of larger clinical trials.

Support (if any)
0347 CBT-I Leads to Changes in Actigraphy and Sleep Diary-Assessed Sleep Parameters in Veterans with Psychosis and Insomnia
Authors: Klingaman Elizabeth , Howell Mary Katherine , Brown Clayton , Li Lan , Kreyenbuhl Julie , Taylor Maddison , Glieger Justine , Vivino Anthony 
Published: May 2023

Abstract

Introduction
Up to 80% of people with psychosis have insomnia. While insomnia worsens psychotic symptoms and functioning, treating insomnia may improve functioning and recovery. Cognitive Behavioral Therapy for Insomnia (CBT-I) is an effective treatment, but there is limited research on CBT-I in people living with psychosis. We developed guidelines and materials for conducting CBT-I with people with psychosis and evaluated actigraphy and sleep diary-measured outcomes in Veterans who participated in an RCT of CBT-I for psychosis.

Methods
Forty-seven Veterans with insomnia and psychosis were randomized to either CBT-I using novel psychosis-specific guidelines and materials (n=26) or to an active treatment control, the Health and Wellness (HW) intervention (n=21). Participants completed both actigraphy and daily sleep logs for two weeks at baseline, post-treatment, and 3-month follow-up.

Results
Using a mixed effects model for repeated measures, mean change from baseline at post and follow-up was compared for CBT-I for psychosis and HW. For actigraphy-measured total sleep time (TST) and time in bed (TIB), and diary-measured TIB, there was a significant decrease in these parameters for the CBT-I group relative to an increase for HW at post (t(1082)=-2.41, p=.016, d=-.38; t(1082)=-2.19, p=.029, d=-.44; t(1318)=-3.19, p=.002, d =-.70, respectively) and in diary-measured TIB at follow-up (t(1318)=-1.97, p=.049, d=-.37. Sleep diary-measured sleep efficiency (SE) increased significantly more in CBT-I than in HW (t(1266)=1.99, p=.047, d=.54) at post. There were no group differences in actigraphy-measured SE, sleep onset latency (SOL), or WASO, or sleep diary-measured TST, SOL, WASO, or number of awakenings at post. There were no other group differences for actigraphy- or diary-measured sleep variables at follow-up, though underpowered due to sample size at the follow-up timepoint.

Conclusion
Results indicate that CBT-I tailored to the needs of people with psychosis can change several actigraphy- and diary-assessed common sleep variables of interest--TST, TIB, and SE. CBT-I for psychosis should be further investigated with a larger randomized controlled trial over a longer time period.

Support (if any)
Time supported by U.S. Department of Veterans Affairs, RR&D-1IK2RX001836, PI: Elizabeth A. Klingaman.
0350 Daridorexant in patients with insomnia disorder: number needed to treat, number needed to harm & likelihood to be helped or harmed
Authors: Chalet François-Xavier , Luyet Pierre-Philippe , Rabasa Cristina , Vaillant Cédric , Saskin Paul , Ahuja Ajay , Citrome Leslie 
Published: May 2023

Abstract

Introduction
Patients with insomnia disorder have difficulty initiating or maintaining sleep and have impaired daytime functioning. Daridorexant is a dual orexin receptor antagonist approved for the treatment of insomnia. This analysis reports the number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH) with daridorexant 25 mg or 50 mg versus placebo over 3 months.

Methods
Phase 3 data from one of two pivotal trials (N=930: randomized 1:1:1 to daridorexant 25 mg, 50 mg, or placebo) were used to calculate NNT, NNH, and LHH. For the NNT analysis, wakefulness after sleep onset, latency to persistent sleep, self-reported total sleep time, the Insomnia Daytime Symptoms and Impacts Questionnaire, and the Insomnia Severity Index were explored. NNT was assessed using a range of clinically meaningful thresholds (CMTs), from minimal clinical improvement (MiCI) to marked clinical improvement. NNH analysis was performed on adverse events (AEs) occurring in &gt;1% of participants in any treatment arm. LHH values were calculated for all NNT outcomes using the NNH estimates for somnolence and fatigue AEs.

Results
At Month 1 and 3, NNT values at MiCI thresholds for daridorexant 50 mg ranged from 5–9 and 6–12, respectively, and were all statistically significantly different versus placebo, indicating a good therapeutic response. Daridorexant 50 mg had at least one NNT &lt; 10 for CMTs across all outcomes. NNTs at MiCI thresholds for daridorexant 25 mg ranged between 7–328 and 8–1666. NNH values for daridorexant 25 and 50 mg were negative or not significantly different from placebo, confirming a good tolerability profile. For a somnolence AE, LHH values ranged from 83.3–200 for daridorexant 50 mg versus placebo. For a fatigue AE, LHH ranged from 4.3–10.2.

Conclusion
Daridorexant 25 mg and 50 mg both have a positive benefit-risk ratio compared with placebo over 3 months. Furthermore, daridorexant 50 mg showed ‘good’ NNT values (i.e. NNT &lt; 10) over all efficacy endpoints in relation to the CMTs. NNH results confirmed the good tolerability profile of both doses.

Support (if any)
Funded by Idorsia Pharmaceutical Ltd.
0351 Differential Effect of Lemborexant and Zolpidem on Wake Across the Night in Patients with Insomnia Disorder
Authors: Roth Thomas , Cheng Jocelyn , Kumar Dinesh , Moline Margaret 
Published: May 2023

Abstract

Introduction
Insomnia can involve difficulty with falling and/or staying asleep; older adults tend to report more sleep maintenance issues. While zolpidem tartrate extended-release 6.25mg (ZOL) is indicated to treat sleep onset and maintenance, data indicate that ZOL may be less effective in the last 2 hours of the night. It is important to understand the differences between ZOL and lemborexant (LEM), a dual-orexin-receptor-antagonist with the same indication. In Study 304 (E2006-G000-304; NCT02783729), LEM treatment significantly improved objective sleep maintenance (wake after sleep onset [WASO] and WASO in the second half of the night) assessed by polysomnography (PSG) over 1 month compared with placebo (PBO) and ZOL in older adults with insomnia disorder. This post-hoc analysis assessed the effect of LEM and ZOL on wake at each hour (H) of an 8-h sleep period.

Methods
Study 304 was a randomized, double-blind, PBO- and active-controlled, parallel-group study in adults ≥55y. Subjects (n=1006) received PBO, LEM 5mg (LEM5) or 10mg (LEM10), or ZOL for 1 month. Wake (minutes) was assessed hourly from paired PSGs during single-blind PBO run-in and post-randomization at nights (NT) 1/2 and NT29/30. Change from baseline (CfB) for H1-8 was analyzed using pooled t-tests.

Results
Between-group baseline wake was similar. On NT1/2 and NT29/30, CfB for LEM10 was significantly greater (less wake) than PBO for all hours except H4 NT29/30. On NT1/2 and NT29/30, CfB for LEM5 was significantly greater than PBO for all hours except H4 NT1/2 and NT29/30 and H8 NT1/2. On NT1/2 and NT29/30, CfB for LEM5 and LEM10 were significantly greater than ZOL during H1,2,7, and 8. CfB for ZOL was not significantly different than PBO except for H2-6 NT1/2 and H3,5,6 NT29/30; CfB for PBO was significantly greater (better) than ZOL during H1 NT29/30.

Conclusion
LEM improves total sleep time by decreasing wake time throughout the night after sleep onset compared to PBO, and at the beginning/end of the night compared to ZOL. These findings support that ZOL may be less effective in maintaining sleep during the last 2 hours of the night compared with LEM in older subjects, especially those with sleep maintenance difficulties.

Support (if any)
Eisai Inc.
0352 Digital cognitive behavioral therapy in treating insomnia in older adulthood: A sub-analysis using individual participant data
Authors: Tarnai Kathryn , Henry Alasdair , Miller Christopher , Waxmonsky Jeanette , Emsley Richard , Espie Colin 
Published: May 2023

Abstract

Introduction
Insomnia prevalence increases across the lifespan with rates reported as high as 40% in the over 65 yo population. Although cognitive behavioral therapy (CBT) for insomnia is the first-line recommended treatment, low accessibility leaves many older adults with less effective treatment options including medication and sleep hygiene. Medication is not recommended due to side effects, which may be more probable in older individuals. Digital CBT (dCBT) for insomnia permits access to first-line treatment; however, little is known about its effectiveness in older adults. We evaluated the effects of fully-automated dCBT on symptoms of insomnia, anxiety, and depression in adults aged 65 and older.

Methods
Individual participant data from prior randomized controlled trials of dCBT for insomnia (Sleepio) were combined for those aged 65+ (range=65-92yo) with insomnia disorder (N=486). Participants received access to dCBT or a control. As the insomnia, anxiety, and depression outcomes were assessed differently across studies, scores were standardized into z-scores. Mixed-effects models estimated the effect of treatment on the combined sleep, depression and anxiety outcomes at post-treatment and follow-up. For studies using the SCI-8, chi-squared tests evaluated insomnia remission rates between groups at post-treatment.

Results
Digital CBT led to significantly greater improvements at post-treatment and follow-up relative to control for the combined sleep (ds≤-1.34, ps&lt;.001) and depression (ds≤-0.35, ps≤.001) outcomes. For the combined anxiety outcome, dCBT led to significantly greater improvements at post-treatment (d=-0.30, p=.004). Those randomized to dCBT were more likely to achieve remission of insomnia (60% vs. 16%, p&lt;.001) at post-treatment.

Conclusion
Fully-automated dCBT for insomnia is effective at improving symptoms of insomnia, anxiety, and depression in adults aged 65+. Digital CBT may therefore serve as a first-line treatment option for older adults with insomnia to improve sleep and broader mental health. Importantly, dCBT may serve as an accessible means for older adults to receive guideline concordant treatment at scale.

Support (if any)
This work was supported in part by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the NHS, NIHR, or Department of Health and Social Care.
0353 Effect of Lemborexant on Sleep Architecture in Adult and Elderly Subjects with Mild to Severe Obstructive Sleep Apnea
Authors: Zammit Gary , Cheng Jocelyn , Hall Nancy , Shah Dhara , Moline Margaret 
Published: May 2023

Abstract

Introduction
Lemborexant (LEM) is a dual-orexin-receptor antagonist approved to treat adults with insomnia. In such patients, LEM increased total sleep, with prominent increases in rapid eye movement (REM). Since patients with obstructive sleep apnea (OSA) may report sleep difficulties and show decreased REM sleep, sleep architecture was analyzed after treatment with LEM.

Methods
Studies 102 and 113 were double-blind, placebo (PBO)-controlled crossover studies in adult and elderly subjects with mild (apnea-hypopnea index [AHI] ≥5 to &lt; 15) or moderate (AHI ≥15 to &lt; 30)/severe (AHI ≥30) OSA, respectively, without insomnia. Subjects were randomized to LEM 10mg (LEM10) or PBO in two 8-night treatment periods (separated by ≥14 days). Least-squares-mean (LSM) for each sleep stage (minutes) was compared across conditions on Days 1 (D1) and 8 (D8). Treatment-emergent adverse events (TEAEs) were recorded.

Results
The analysis set comprised 39 subjects with mild OSA and 33 with moderate/severe OSA. On both days, total sleep time was significantly higher in the LEM condition in subjects with mild (D1: LEM10, 434.08; PBO, 385.46; P&lt; 0.0001; D8: LEM10, 415.90; PBO, 386.85; P=0.003) and moderate/severe (D1: LEM10, 423.10; PBO, 385.48; P&lt; 0.0001; D8: LEM10, 416.96; PBO, 385.57; P=0.001) OSA. Compared with PBO, total non-REM sleep significantly increased only on D1 in subjects with mild OSA (D1: LEM10, 330.57; PBO, 308.55; P=0.001; D8: LEM10, 323.77; PBO, 308.97; P=0.060) but on both days in subjects with moderate/severe OSA (D1: LEM10, 343.23; PBO, 327.45; P=0.006; D8: LEM10, 341.83; PBO, 322.48; P=0.018). Total REM sleep significantly increased in subjects with mild (D1: LEM10, 103.59; PBO, 76.91; P&lt; 0.0001; D8: LEM10, 92.13; PBO, 77.93; P=0.004) and moderate/severe (D1: LEM10, 79.87; PBO, 58.03; P&lt; 0.0001; D8: LEM10, 75.13; PBO, 62.69; P=0.006) OSA. REM latency was significantly decreased on both days in subjects with mild OSA (D1: LEM10, 51.96; PBO, 83.36; P&lt; 0.0001; Day 8: LEM10, 67.52; PBO, 102.34; P=0.005) and only on D1 in subjects with moderate/severe OSA (D1: LEM10, 72.13; PBO, 98.90; P=0.029; D8: LEM10, 90.42; PBO, 106.63; P=0.242). LEM was well-tolerated; most TEAEs were mild.

Conclusion
In OSA subjects without insomnia, LEM nevertheless increased total sleep, non-REM, and REM sleep versus PBO.

Support (if any)
Eisai Inc.
0357 Pimavanserin 34mg at Bedtime for Insomnia in Veterans with Post-traumatic Stress Disorder: Open-label Case Series
Authors: Jones Melissa , Agrawal Ritwick , Sharafkhaneh Amir , Elammari Mohamed , Zhao Zhifang , Jorge Ricardo , Marsh Laura 
Published: May 2023

Abstract

Introduction
There is a critical need for effective and feasible interventions to address insomnia associated with post-traumatic stress disorder (PTSD). Several lines of evidence suggest that pimavanserin, a 5-HT2A inverse agonist approved by the FDA for the treatment of Parkinson's disease psychosis, may benefit PTSD-related sleep disturbances. We conducted a pilot, open-label study of pimavanserin 34mg at bedtime for the treatment of PTSD-associated insomnia to preliminarily assess the feasibility of this intervention and tolerability of our protocol (NCT04188392).

Methods
Adult, male and female Veterans with chronic insomnia disorder and PTSD received fixed dose, open label pimavansern 34mg at bedtime for 6 weeks. Subjects completed 7 days of actigraphy monitoring and two consecutive in-lab polysomnograms (PSGs) pre-treatment. Safety and adherence were assessed in-person at weeks 3 and 6 and otherwise weekly via telephone. Actigraphy monitoring and a closeout PSG were repeated at week 6. Primary outcomes were recruitment and retention rates, defined as the total number of subjects recruited into treatment (goal n=6) and treatment completion rates (goal 75%), respectively.

Results
A total of 6 subjects (mean age 35.3 [S.D. 6.3] years, 2 [33.3%] female, 2 (33.3%] black or African American, 2 [33.3%] Hispanic, 4 [66.7%] comorbid depression) were recruited over 5.8 months. One subject was found to have mild OSA (AHI 5.6). Insomnia Severity Index (ISI) scores were in the severe range for 4 of 6 [66.7%] subjects. All subjects (100%) completed treatment. There were no serious adverse events or medication discontinuations due to adverse events. Preliminary analyses revealed a greater tend toward improvement on subjective measures of insomnia compared to objective sleep measures.

Conclusion
This open-label case series provides preliminary evidence for the tolerability of pimavanserin in Veterans with PTSD-associated insomnia and feasibility of our protocol. A larger, randomized controlled trial is needed to detect a meaningful clinical difference in insomnia severity following treatment with pimavanserin.

Support (if any)
Michael E. DeBakey VA Medical Center Seed & Bridge Award; Center for Alzheimer's and Neurodegenerative Diseases, Baylor College of Medicine
0361 Sleep Disturbances in a Sample of Pregnant Military Mothers
Authors: Burns Rosemary Estevez , Kokonda Manasa , Williams Justin , Meers Jessica , Krunnfusz Andrea , Ellis Jordan , Aycock Chase , Jones John , Nowakowski Sara 
Published: May 2023

Abstract

Introduction
Pregnant civilians report poor sleep quality, insufficient nighttime sleep, sleep fragmentations, and significant daytime sleepiness. Sleep disturbances are associated with increased risk of adverse outcomes during pregnancy (e.g., pre-eclampsia) and labor and delivery outcomes (e.g., cesarean section). The military population is at increased risk of developing sleep disorders. The military population is at increased risk of developing sleep disorders. We aimed to identify the prevalence of insomnia symptoms in a sample of active duty and military dependent pregnant women.

Methods
Pregnant individuals (N=100) were recruited from large Military Treatment Facility in Texas. Participants were predominantly between ages 25-29 (32%), White (67%), Non-Hispanic (75%), in their second trimester (56%), Active Duty Air Force (48%), Enlisted (44%), and married (87%). In this cross-sectional study, participants completed a survey containing the Insomnia Severity Index (ISI), Pre/Peri pregnancy sleep, and obstetric care questions. Ordinal logistic regression was performed using SAS to determine if pregnancy trimester predicted outcomes including: insomnia, poor sleep quality, and perceived sleep-related impairment.

Results
Twenty percent presented with moderate/severe insomnia per ISI. The odds of having Insomnia (Severe vs No/absence) are 8.09x higher in the third trimester than first trimester (p=0.002). The odds of having poor sleep quality during pregnancy are 33.17x higher in the third trimester compared to first trimester (p&lt;.0001). Mothers in the third trimester were 1.02x more likely to perceive other mothers as having significant sleep problems than those in the first trimester (p=0.02). Despite these reported sleep difficulties, 98% were not referred for a sleep consultation visit.

Conclusion
Findings suggested 20% of pregnant individuals associated with the U.S. Military experienced significant sleep concerns with no active plan for treatment. Individuals in their third trimester were more likely to have high ISI scores, report poorer sleep quality, and more likely to suspect significant sleep problems as common throughout pregnancy. Pregnancy is a critical period for intervention as chronic insomnia diminishes military readiness and compromises health. Insomnia prevention and intervention is greatly needed and could be integrated into obstetric clinics early in pregnancy.

Support (if any)
This work is supported by the VA HSR&D Center for Innovations in Quality, Effectiveness and Safety (CIN 13-413).
0365 The Effectiveness of Digital Cognitive Behavioral Therapy for Insomnia, Fatigue, and Quality of Life in Cancer Patients
Authors: Miller Christopher , Waxmonsky Jeanette , Henry Alasdair , Emsley Richard , Espie Colin 
Published: May 2023

Abstract

Introduction
The emotional, psychological and financial challenges of a cancer diagnosis profoundly affect patients and contribute to sleep difficulties. Insomnia affects 31%-54% of those newly diagnosed or undergoing treatment, and persists up to 5 years after treatment for cancer. Cognitive behavioral therapy (CBT) for insomnia is effective for sleep and insomnia outcomes, with no difference in outcomes for in-person or self-help CBT. Trials of digital CBT (dCBT) have recruited breast cancer survivors from Denmark and past pilot work did not identify statistically significant effects for fatigue and quality of life in US cancer survivors with insomnia. This study examined the effectiveness of a fully automated digital therapeutic (Sleepio) for improving insomnia, fatigue, and quality of life in patients with cancer from the US, UK, and Australia.

Methods
This is a secondary analysis of participants (n=70) with insomnia who self-reported a cancer diagnosis before randomization in a large effectiveness trial of dCBT for insomnia. Participants were randomized to receive either dCBT or a sleep hygiene education control. Insomnia (SCI-8), fatigue (FFS), and global health-related quality of life (PROMIS-10) were evaluated at baseline, 8-weeks post treatment and 24-weeks follow-up. Effect estimates are mean group differences, adjusted for baseline scores estimated using regression models.

Results
Digital CBT was superior to control for reducing symptoms of insomnia and fatigue at both post-treatment and follow-up (all p&lt; 0.05). For the dCBT group, global PROMIS-10 scores were improved, although not significantly, at post-treatment (p=0.076), but were significantly higher at follow-up (p&lt; 0.05).

Conclusion
Digital CBT was effective for reducing symptoms of insomnia and fatigue in patients with cancer and results were maintained after five and a half months. Significant improvements in global health-related quality of life scores at follow-up suggest effects extend beyond improvements to sleep. Findings may benefit patients with cancer as dCBT may provide scalable access to an effective treatment without contraindications. Further research is needed to understand the mechanisms and value of improving sleep in those with cancer and sleep difficulty.

Support (if any)
Big Health Inc.