Varenicline, a partial nicotinic receptor agonist, for the treatment of excessive daytime sleepiness in Parkinson*s disease: a placebo-controlled cross-over study

Sleep disturbances are common in Parkinson*s disease (PD) and include excessive
daytime sleepiness (EDS) that has been reported in up to 50% of patients.
Relatively little therapeutic research has addressed the problem of EDS and
current treatment is largely aimed at reducing the dose of dopaminergic
medication while trying to maintain sufficient motor control which
unfortunately often fails. Apart from degeneration of
dopaminergic neurons, a decrease in cholinergic projections to the brain
arousal areas may be at least partly responsible for the occurrence of EDS in
PD. Smoking in narcoleptic patients diminishes sleep attacks and EDS , thus one
may hypothesize that nicotinergic stimulation of the brain arousal areas may
improve EDS in PD. Therefore the effect of varenicline, an alpha4beta2
nicotinic receptor partial agonist (nAChR), on EDS in PD will be studied in a
placebo-controlled cross-over study.

This study is aimed to determine the efficacy of varenicline in reducing EDS in
PD patients.

The study is a randomized, double blind, placebo-controlled clinical trial with
a within-subject crossover design.

Patients will be randomly assigned to start an active treatment or placebo and
complete two periods of four weeks with a washout period of two weeks.

Patient characteristics will be obtained among several scales on sleep, mental
state and quality of life. The patients will undergo a polysomnography and a
safety evaluation including ECG and renal function. MWT and plasma levels are
measured in the challenge fase and steady state condition after four weeks of
treatment. After a two week washout period all procedures are repeated for the
cross-over study. Adverse events may include nausea, headache, insomnia and
abnormal dreams and will be carefully monitored.