The Effects of Trazodone on Sleep Apnea Severity
Condition: Sleep Apnea, Obstructive
MeSH terms: Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive
Study type: Interventional

Summary: 
      In Obstructive sleep apnea (OSA), the upper airway closes over and over again during sleep.
      This leads to disrupted sleep (waking up during the night), daytime sleepiness, and an
      increased risk for developing high blood pressure. Currently, the best treatment for
      obstructive sleep apnea is sleeping with a mask that continuously blows air into the nose
      (i.e. Continuous positive airway pressure [CPAP] treatment). While CPAP treatment stops the
      upper airway from closing in most people, many people have difficulty sleeping with the mask
      in place and therefore do not use the CPAP treatment. This research study is being conducted
      to learn whether using a sedative will improve OSA severity by altering some of the traits
      that are responsible for the disorder.
    

Detailed description: 
      Obstructive sleep apnea (OSA) is characterized by repetitive collapse or 'obstruction' of the
      pharyngeal airway during sleep. These obstructions result in repetitive hypopneas/apneas and
      intermittent hypoxia/hypercapnia, as well as surges in sympathetic activity. Such processes
      disturb normal sleep and impair neurocognitive function, often resulting in excessive daytime
      sleepiness and decreased quality of life. Furthermore, OSA is associated with cardiovascular
      morbidity and mortality, making OSA a major health concern.

      Current evidence suggests that OSA pathogenesis involves the interactions of at least four
      physiological traits comprising: 1) the pharyngeal anatomy and its propensity towards
      collapse. This collapsibility of the upper airway is measured as the critical closing
      pressure or PCRIT. 2) the ability of the upper airway dilator muscles to activate and reopen
      the airway during sleep (i.e. neuromuscular compensation) measured as the increase in upper
      airway electromyography (EMG) activity above the baseline level. 3) the arousal threshold
      from sleep (i.e. the propensity for hypopneas/apneas to lead to arousal and fragmented sleep)
      measured as the epiglottic pressure occurring just at the time of arousal and 4) the
      stability of the ventilatory feedback loop (i.e. loop gain). Continuous positive airway
      pressure (CPAP) is the most common treatment for OSA but it is often poorly tolerated; only
      ~50% of patients diagnosed with OSA continue therapy beyond 3 months. Given this limitation,
      alternative approaches have been tested and have generally focused on the use of oral
      appliances and upper airway surgery.

      In addition to these alternative therapies, the use of pharmacological agents for the
      treatment of OSA has been gaining widespread interest. Previous data have shown that the
      non-myorelaxant hypnotic trazodone increases the arousal threshold however its effects on
      sleep apnea severity remain unclear. Based on studies showing that increasing the arousal
      threshold with a different hypnotic improves sleep apnea severity, we hypothesize that
      trazodone will increase the arousal threshold and this will be associated with an improvement
      in sleep apnea severity.

      Therefore the overall aim of this study is to examine the effects that trazodone has on OSA
      severity.

      STUDY DESIGN:

      A double-blinded randomized control design will be used. Initially, participants will be
      randomized to the trazodone or placebo arm where they will have both a clinical
      polysomnography (PSG) with the addition of an epiglottic pressure cathether. The purpose of
      the clinical PSG is to determine the severity of OSA (i.e. AHI) and the epiglottic catheter
      allows the calculation of the arousal threshold to be completed.

      During the trazodone arm, participants will be given trazodone (100mg by mouth) to take
      before bed. During the placebo arm, subjects will be given a placebo to take before bed.

      Participants will have at least a 1-week washout period before cross over to the next arm of
      the study whereby the clinical PSG will be repeated. In total each subject will be studied
      for 2 nights.
    

Intervention name(s): Placebo pill; Trazodone
Intervention type(s): Drug; Drug
Intervention description(s): Subjects will receive a sugar pill during the placebo arm; Subjects will receive trazodone during one of their treatment arm studies
Other intervention name(s): Sugar pill
Intervention MeSH terms: Trazodone
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Apnea- Hypopnea index; Arousal Threshold