||5R21CA096631-02 Interpret this number
||University Of California San Diego
||Effects of Opioids on Sleep and Fatigue
DESCRIPTION (provided by applicant): The goal of this R21 application is to refine an experimental design to examine the impact of commonly used pain medications on sleep and next-day fatigue. However, before such studies can be conducted in patients with acute or chronic pain associated with cancer or other severe chronic illness, crucial information is needed to optimize the study design. This proposal seeks to answer certain experimental methodological design questions that can be safely,
quickly, and inexpensively addressed in healthy volunteers. This R21 application will generate data guiding the research design and power estimates for subsequent RO1 applications intended to address the impact of pain medication on sleep and fatigue in patients with acute or chronic pain. There are 5 specific aims:
1. Characterize the effect of a typical nighttime dose of MS-Contin and methadone on cytokines, polysomnographic sleep and on rest/activity patterns in healthy volunteers:
2. Characterize daytime fatigue the day after drug administration with self-reported measure of fatigue and mood
3. Characterize neuropsychological performance on the day after drug administration.
4. Estimate the covariance structure of sleep measures to assess the comparative advantages of a crossover or parallel groups design.
5. Evaluate the necessity of repeated first nights and whether this is the optimum design for follow-up studies.
Over a two-year period, 50 healthy volunteer subjects will be examined with polysomnography, actigraphy, and neuropsychological tests. Data will be collected on self-reported mood and fatigue, as well as proinflammatory cytokine levels (IL-6, IL-1beta, and TNF-alpha. The study design involves a double-blind, placebo-controlled crossover.
Each individual will be admitted to the UCSD GCRC on 3 pairs of nights. Each admission will feature an acclimation night in the sleep laboratory followed by a night providing placebo, MS-Contin (15 rag) or methadone (5 mg). On the morning after each dosing subjects will complete fatigue and mood ratings and will perform a brief neuropsychological test battery. They will also undergo actigraphy monitoring for 3 continuous days to examine whether there are subtle lingering effects of the drugs. Blood levels ofproinflammatory cytokines will be obtained at various points before and after drug dosing and the next morning to test the hypothesis that opioid-induced changes in these cytokines are associated with sleep disruption and increased fatigue.
Taking fatigue seriously, II: variability in fatigue levels in cancer patients.
, Ancoli-Israel S.
, Ayalon L.
, Elsmore T.F.
, Gruen W.
Psychosomatics, 2007 May-Jun; 48(3), p. 247-52.
The effect of opioids on sleep architecture.
, Norman D.
, DeJardin D.
, Wallace M.S.
Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 2007-02-15; 3(1), p. 33-6.
Assessing the trade-offs between crossover and parallel group designs in sleep research.
, Moore P.
, Dimsdale J.E.
Journal of sleep research, 2006 Dec; 15(4), p. 348-57.