Preventing the Inflammatory Response to Experimentally-induced Insomnia Symptoms
Condition: Insomnia
MeSH terms: Sleep Initiation and Maintenance Disorders
Study type: Interventional
Phase: Early Phase 1

Summary: 
      The main purpose of this study is to learn about the effects of sleep disruption (two days in
      a row where sleep is shortened and disrupted) on inflammation, mood (how you feel), and pain
      processing (your own experiences/perceptions of pain). In this research project, we are
      trying to figure out if we can change the effects of sleep disruption on inflammation, mood,
      and pain. Therefore, we will study whether taking a low-dose aspirin pill every day over 2
      weeks can change how we respond to sleep disruption. For example, does the sensitivity to
      pain (e.g., how intense the feeling of pain is if we put our hand in very hot or very cold
      water) change with sleep disruption, and can low-dose aspirin influence this change. We are
      also interested in seeing how inflammation changes in relation to your own perceived
      experience of pain.
    

Detailed description: 
      Sleep that is deficient in quantity or quality leads to upregulation of inflammatory markers
      (Mullington et al., 2010). In particular, interleukin (IL)-6 and prostaglandin (PG) E2 are
      elevated in experimental models of sleep restriction or total sleep deprivation, as well as
      in insomnia. Inflammation is thought to be a key mechanism through which insufficient sleep
      increases the risk of developing or exacerbating various disorders, including cardiovascular
      and metabolic disorders (Mullington et al., 2009), as well as pain-related disorders (Haack
      et al., 2009c). With respect to pain, markers such as IL-6 and PGE2 are able to sensitize
      pain transmission neurons, thereby increasing their responsiveness to stimulation. In the
      context of insufficient sleep, both IL-6 and PGE2 have been shown to be associated with
      increased spontaneous pain (Haack et al., 2007;Haack et al., 2009a), suggesting their
      mediating role in pain amplification as a consequence of insufficient sleep.

      These findings raise the question of whether pain amplification can be dampened by preventing
      the inflammatory increase in response to insufficient sleep.

      The primary goal of this pilot project is to gather preliminary support for the hypothesis
      that deficient sleep leads to pain amplification through an inflammatory mechanism.

      In addition to the primary goal of this proposal, the secondary goal is to gather preliminary
      data on the effects of aspirin on blood pressure regulation. Cardiovascular disease is the
      leading cause of death in the United States. A modest reduction of blood pressure (BP; i.e.,
      3 to 5 mmHg) in the population will produce a significant fall in serious cardiovascular
      events (Turnbull, 2003). It has been reported that low-dose aspirin may significantly reduce
      BP (i.e., 6 to 7 mmHg) when taken at bedtime (Hermida et al., 1994;Hermida et al.,
      1997;Hermida et al., 2003b;Hermida et al., 2003a;Hermida et al., 2005a;Hermida et al.,
      2005b). Aspirin, when taken at bedtime, may modulate 24h blood pressure by decreasing the
      nocturnal rise of renin-angiotensin-aldosterone system (RAAS) activity (Snoep et al., 2009)
      and attenuating the nocturnal drop in nitric oxide (NO) production (Hermida et al., 2005b).
      However, the underlying mechanisms are still unknown. Therefore, the second goal of this
      pilot project is to investigate the potential mechanisms contributing to BP reduction in
      response to aspirin taken at bedtime.
    

Intervention name(s): Aspirin; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 81mg aspirin daily at bedtime over a 2 week period; pill that looks like aspirin without the effects of aspirin
Other intervention name(s): non-steroidal anti-inflammatory drug
Intervention MeSH terms: Aspirin; Anti-Inflammatory Agents, Non-Steroidal; Anti-Inflammatory Agents
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: sleep, insomnia, inflammation, pain; Insomnia symptom induction/placebo; Insomnia symptom induction/aspirin