Hans P A Van Dongen, Eileen B Leary, Christopher Drake, Richard Bogan, Judith Jaeger, Russell Rosenberg, Caroline Streicher, Herriot Tabuteau
{"title":"SHARP 研究结果：一项随机、安慰剂对照、双盲、重复测量、交叉的 IV 期临床试验，研究促醒剂 Solriamfetol 对伴有白天过度嗜睡和认知功能障碍的阻塞性睡眠呼吸暂停患者认知功能的影响。","authors":"Hans P A Van Dongen, Eileen B Leary, Christopher Drake, Richard Bogan, Judith Jaeger, Russell Rosenberg, Caroline Streicher, Herriot Tabuteau","doi":"10.1016/j.chest.2024.10.050","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Obstructive sleep apnea (OSA) causes episodes of fragmented sleep and intermittent hypoxia and leads to excessive daytime sleepiness (EDS). Deficits in cognitive function are a troublesome symptom in patients with OSA and EDS.</p><p><strong>Research question: </strong>How does solriamfetol affect cognitive function in patients with cognitive impairment associated with OSA and EDS?</p><p><strong>Study design and methods: </strong>SHARP was a phase 4, randomized, double-blind, placebo-controlled, crossover trial. Participants (N=59) were randomized to receive placebo or solriamfetol (75 mg/day for 3 days, then 150 mg/day) for 2 weeks, with crossover separated by a 1-week washout. Efficacy measures included the Coding subtest, comparable to the Digit Symbol Substitution Test, of the Repeatable Battery for the Assessment of Neuropsychological Status (DSST RBANS), the British Columbia Cognitive Complaints Inventory (BC-CCI), Patient Global Impression of Severity (PGI-S), and Epworth Sleepiness Scale (ESS). The primary endpoint was change from baseline in average post-dose DSST RBANS scores. Secondary endpoints were changes from baseline in BC-CCI, PGI-S, ESS, and DSST RBANS scores at 2, 4, 6, and 8 hours post-dose. Safety was monitored by treatment-emergent adverse events (TEAEs).</p><p><strong>Results: </strong>Solriamfetol significantly improved post-dose average DSST RBANS scores compared with placebo (P=0.009; effect size [Cohen's d] 0.37). When evaluated at each 2-hour timepoint, cognitive function was significantly improved at 2, 6, and 8 hours after dosing (all P<0.05). During solriamfetol treatment, there were significant improvements in BC-CCI (P=0.002; d=0.45), PGI-S (P=0.0mixed; d=0.29), and ESS (P=0.004; d=0.40) compared with placebo. The most common TEAEs were nausea (7%) and anxiety (3%).</p><p><strong>Interpretation: </strong>SHARP demonstrated that solriamfetol can improve objective and subjective measures of cognitive function in patients with cognitive impairment associated with OSA and EDS.</p><p><strong>Clinical trial registration: </strong>NCT04789174; EudraCT: 2020-004243-92.</p>","PeriodicalId":9782,"journal":{"name":"Chest","volume":" ","pages":""},"PeriodicalIF":9.5000,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Results of the SHARP Study: A Randomized, Placebo-Controlled, Double-Blind, Repeated-Measures, Crossover, Phase IV Clinical Trial of the Effect of the Wake-Promoting Agent Solriamfetol on Cognitive Function in Obstructive Sleep Apnea With Excessive Daytime Sleepiness and Cognitive Impairment.\",\"authors\":\"Hans P A Van Dongen, Eileen B Leary, Christopher Drake, Richard Bogan, Judith Jaeger, Russell Rosenberg, Caroline Streicher, Herriot Tabuteau\",\"doi\":\"10.1016/j.chest.2024.10.050\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Obstructive sleep apnea (OSA) causes episodes of fragmented sleep and intermittent hypoxia and leads to excessive daytime sleepiness (EDS). 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Results of the SHARP Study: A Randomized, Placebo-Controlled, Double-Blind, Repeated-Measures, Crossover, Phase IV Clinical Trial of the Effect of the Wake-Promoting Agent Solriamfetol on Cognitive Function in Obstructive Sleep Apnea With Excessive Daytime Sleepiness and Cognitive Impairment.
Background: Obstructive sleep apnea (OSA) causes episodes of fragmented sleep and intermittent hypoxia and leads to excessive daytime sleepiness (EDS). Deficits in cognitive function are a troublesome symptom in patients with OSA and EDS.
Research question: How does solriamfetol affect cognitive function in patients with cognitive impairment associated with OSA and EDS?
Study design and methods: SHARP was a phase 4, randomized, double-blind, placebo-controlled, crossover trial. Participants (N=59) were randomized to receive placebo or solriamfetol (75 mg/day for 3 days, then 150 mg/day) for 2 weeks, with crossover separated by a 1-week washout. Efficacy measures included the Coding subtest, comparable to the Digit Symbol Substitution Test, of the Repeatable Battery for the Assessment of Neuropsychological Status (DSST RBANS), the British Columbia Cognitive Complaints Inventory (BC-CCI), Patient Global Impression of Severity (PGI-S), and Epworth Sleepiness Scale (ESS). The primary endpoint was change from baseline in average post-dose DSST RBANS scores. Secondary endpoints were changes from baseline in BC-CCI, PGI-S, ESS, and DSST RBANS scores at 2, 4, 6, and 8 hours post-dose. Safety was monitored by treatment-emergent adverse events (TEAEs).
Results: Solriamfetol significantly improved post-dose average DSST RBANS scores compared with placebo (P=0.009; effect size [Cohen's d] 0.37). When evaluated at each 2-hour timepoint, cognitive function was significantly improved at 2, 6, and 8 hours after dosing (all P<0.05). During solriamfetol treatment, there were significant improvements in BC-CCI (P=0.002; d=0.45), PGI-S (P=0.0mixed; d=0.29), and ESS (P=0.004; d=0.40) compared with placebo. The most common TEAEs were nausea (7%) and anxiety (3%).
Interpretation: SHARP demonstrated that solriamfetol can improve objective and subjective measures of cognitive function in patients with cognitive impairment associated with OSA and EDS.
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