Many patients (74-98%) with Parkinson's disease (PD) experience significant sleep disturbances, the etiology of which is not fully understood. The purpose of this multi-site, double blind study is to compare the effects of melatonin at two different doses (5mg and 50mg) versus placebo on nocturnal sleep. The clinical design is a placebo-controlled, double cross-over trial. The primary dependent variables are wake time after sleep onset during the major nocturnal sleep episode, mean duration of nocturnal awakenings, and sleep onset latency. The following hypotheses will be tested: 1) Melatonin will decrease wake time after sleep onset (in minutes) during the major nocturnal sleep episode compared to placebo; 2) Melatonin will decrease the mean duration of nocturnal awakenings compared to placebo; 3) Melatonin will decrease sleep onset latency compared to placebo; 4) The higher dose of melatonin (50mg) will produce a greater decrease in wake time after sleep onset, mean duration of nocturnal awakenings, and sleep onset latency than the lower dose (5mg). Secondary aims include assessment of: subject's subjective evaluation of their sleep, daytime alertness, and level of function; and any adverse events associated with melatonin related to its safety and tolerability. Subjects (n=40) with idiopathic PD and no evidence of depression, cognitive impairment, or primary sleep disorders will participate in the 9-week protocol. During each 2-week treatment period, subjects will take melatonin 5mg, melatonin 50mg, or placebo capsules (administered in random order), with a 1-week washout between treatments. Primary dependent variables will be assessed using the Advanced Mini Motionlogger (Actigraph); secondary dependent variables will be assessed by a variety of instruments and questionnaires. A two-way repeated measures ANOVA design will be used to test the hypotheses associated with the primary study aims. Post-hoc contrasts using the Bonferoni criteria will be used to examine the three possible pairwise comparisons (p vs. 5, p vs. 50, 5 vs. 50) to determine where differences exist. Similar analyses and descriptive statistics will be used to analyze data for the secondary aims. This research will lead to the development of safer, more physiologic therapies for treating sleep disturbances in patients with PD.
| Dowling, Glenna A; Mastick, Judith; Colling, Eric et al. (2005) Melatonin for sleep disturbances in Parkinson's disease. Sleep Med 6:459-66 |
