Douglas N Greve1, Stephen P Duntley2, Linda Larson-Prior3, Andrew D Krystal4, Michele T Diaz5, Sean P A Drummond6, Stephen G Thein7, Clete A Kushida8, Ronghua Yang9, Robert J Thomas10. 1. Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Charlestown, MA. 2. Washington University School of Medicine, Department of Neurology, St. Louis, MO. 3. Washington University School of Medicine, Department of Radiology, St. Louis, MO. 4. Duke University Medical Center, Durham, NC. 5. Duke University Medical Center, Brain Imaging and Analysis Center, Durham, NC. 6. University of California and Veterans Affairs San Diego Healthcare System, San Diego, CA. 7. Pacific Research Network, Inc., San Diego, CA. 8. Stanford School of Medicine, Stanford Sleep Medicine Center, Redwood City, CA. 9. Teva Branded Pharmaceutical Products R&D, Inc., Frazer, PA. 10. Beth Israel Deaconess Medical Center, Boston, MA.
Abstract
STUDY OBJECTIVE: To assess the effect of armodafinil on task-related prefrontal cortex activation using functional magnetic resonance imaging (fMRI) in patients with obstructive sleep apnea (OSA) and excessive sleepiness despite continuous positive airway pressure (CPAP) therapy. METHODS: This 2-week, multicenter, prospective, randomized, double-blind, placebo-controlled, parallel-group study was conducted at five neuroimaging sites and four collaborating clinical study centers in the United States. Patients were 40 right-handed or ambidextrous men and women aged between 18 and 60 years, with OSA and persistent sleepiness, as determined by multiple sleep latency and Epworth Sleepiness Scale scores, despite effective, stable use of CPAP. Treatment was randomized (1:1) to once-daily armodafinil 200 mg or placebo. The primary efficacy outcome was a change from baseline at week 2 in the volume of activation meeting the predefined threshold in the dorsolateral prefrontal cortex during a 2-back working memory task. The key secondary measure was the change in task response latency. RESULTS: No significant differences were observed between treatment groups in the primary or key secondary outcomes. Armodafinil was generally well tolerated. The most common adverse events (occurring in more than one patient [5%]) were headache (19%), nasopharyngitis (14%), and diarrhea (10%). CONCLUSIONS:Armodafinil did not improve fMRI-measured functional brain activation in CPAP-treated patients with OSA and excessive sleepiness. STUDY REGISTRATION: Double-Blind, Placebo-Controlled, Functional Neuroimaging Study of Armodafinil (200 mg/Day) on Prefrontal Cortical Activation in Patients With Residual Excessive Sleepiness Associated With Obstructive Sleep Apnea/Hypopnea.
RCT Entities:
STUDY OBJECTIVE: To assess the effect of armodafinil on task-related prefrontal cortex activation using functional magnetic resonance imaging (fMRI) in patients with obstructive sleep apnea (OSA) and excessive sleepiness despite continuous positive airway pressure (CPAP) therapy. METHODS: This 2-week, multicenter, prospective, randomized, double-blind, placebo-controlled, parallel-group study was conducted at five neuroimaging sites and four collaborating clinical study centers in the United States. Patients were 40 right-handed or ambidextrous men and women aged between 18 and 60 years, with OSA and persistent sleepiness, as determined by multiple sleep latency and Epworth Sleepiness Scale scores, despite effective, stable use of CPAP. Treatment was randomized (1:1) to once-daily armodafinil 200 mg or placebo. The primary efficacy outcome was a change from baseline at week 2 in the volume of activation meeting the predefined threshold in the dorsolateral prefrontal cortex during a 2-back working memory task. The key secondary measure was the change in task response latency. RESULTS: No significant differences were observed between treatment groups in the primary or key secondary outcomes. Armodafinil was generally well tolerated. The most common adverse events (occurring in more than one patient [5%]) were headache (19%), nasopharyngitis (14%), and diarrhea (10%). CONCLUSIONS:Armodafinil did not improve fMRI-measured functional brain activation in CPAP-treated patients with OSA and excessive sleepiness. STUDY REGISTRATION: Double-Blind, Placebo-Controlled, Functional Neuroimaging Study of Armodafinil (200 mg/Day) on Prefrontal Cortical Activation in Patients With Residual Excessive Sleepiness Associated With Obstructive Sleep Apnea/Hypopnea.