Effect of armodafinil on cortical activity and working memory in patients with residual excessive sleepiness associated with CPAP-Treated OSA: a multicenter fMRI study.

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.

• Authors: Douglas N Greve, Stephen P Duntley, Linda Larson-Prior, Andrew D Krystal, Michele T Diaz, Sean P A Drummond, Stephen G Thein, Clete A Kushida, Ronghua Yang, Robert J Thomas
• Journal: Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine (J Clin Sleep Med) Vol. 10 Issue 2 Pg. 143-53 (Feb 15 2014) ISSN: 1550-9397 [Electronic] United States
• PMID: 24532997 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Benzhydryl Compounds
• Wakefulness-Promoting Agents
• Modafinil

Topics

• Adolescent
• Adult
• Benzhydryl Compounds (pharmacology)
• Cerebral Cortex (drug effects, physiopathology)
• Continuous Positive Airway Pressure (methods)
• Disorders of Excessive Somnolence (complications)
• Double-Blind Method
• Female
• Humans
• Magnetic Resonance Imaging (methods)
• Male
• Memory, Short-Term (drug effects)
• Middle Aged
• Modafinil
• Prospective Studies
• Sleep Apnea, Obstructive (complications, therapy)
• Treatment Outcome
• Wakefulness-Promoting Agents (pharmacology)
• Young Adult