Varenicline Treatment for Excessive Daytime Sleepiness in Parkinson's Disease

Study Overview
=================
Brief Summary
-----------------
The effect of varenicline, an alpha4beta2 nicotinic receptor partial agonist on excessive daytime sleepiness in Parkinson's disease will be studied in a randomized, double blind, placebo-controlled clinical trial with a within-subject crossover design.

Detailed Description
-----------------
Sleep disturbances are common in Parkinson's disease and include excessive daytime sleepiness that has been reported in up to 50% of patients. Relatively little therapeutic research has addressed the problem of excessive daytime sleepiness 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 excessive daytime sleepiness in Parkinson's disease. Smoking in narcoleptic patients diminishes sleep attacks and excessive daytime sleepiness , thus one may hypothesize that nicotinergic stimulation of the brain arousal areas may improve excessive daytime sleepiness in Parkinson's disease. Therefore the effect of varenicline, an alpha4beta2 nicotinic receptor partial agonist, on excessive daytime sleepiness in Parkinson's disease will be studied in a placebo-controlled cross-over study.

Official Title
-----------------
Varenicline, a Partial Nicotinic Receptor Agonist for the Treatment of Excessive Daytime Sleepiness in Parkinson's Disease: a Placebo-controlled Cross-over Pilot Study

Conditions
-----------------
Parkinson's Disease

Intervention / Treatment
-----------------
* Drug: Varenicline
* Drug: Placebo (for varenicline)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: idiopathic Parkinson's Disease according to clinical diagnostic criteria United Kingdom Parkinson's Disease Society Brain Bank receiving stable Parkinson's medications for at least four weeks before and throughout study suffering Excessive Daytime Sleepiness, defined by a score of >10 on the Epworth Sleeping Scale written informed consent Exclusion Criteria: Parkinson's Disease patients receiving medications with known central depressant effects (benzodiazepines, neuroleptics, anticholinergics) dementia defined by a Mini Mental State Examination <24 depression defined by a Beck Depression Inventory >16 a known diagnosis of sleep apnea or narcolepsy current smoking or smoking cessation in past 6 months presence of contra-indications for treatment with varenicline, including: known psychiatric diseases such as panic disorder, psychosis, bipolar disorder, eating disorder and alcohol or drug abuse unstable angina, a history of cardiac disease or stroke in previous 6 months severe renal failure (glomerular filtration rate ≤ 30 ml/min) insulin-dependent diabetes
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Varenicline<br>Varenicline capsule 1 mg BID | Drug: Varenicline<br>* Tablet 1 mg BID<br>* Other names: Champix;|
| Placebo Comparator: Placebo<br>Placebo capsule | Drug: Placebo (for varenicline)<br>* Tablet 1 mg BID<br>* Other names: Placebo;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daytime sleepiness | Epworth Sleepiness Scale | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sleep quality | Pittsburgh Sleep Quality Index | 4 weeks | 
| Fatigue | Fatigue Severity Scale | 4 weeks | 
| Involuntary movements | Abnormal Involuntary Movements Scale | 4 weeks | 
| Quality of life | Medical Outcomes Study 36-Item Short-Form Health Survey | 4 weeks | 
| Sleep latency | Maintenance of Wakefulness Test | 4 weeks | 
| Pharmacodynamics assessed by computerized test battery |  | 4 weeks | 
| Error score | Sustained Attention to Response Test | 4 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Parkinson's disease, Varenicline, Excessive daytime sleepiness