Parkinson's Disease
Conditions
Keywords
Parkinson's disease, Varenicline, Excessive daytime sleepiness
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.
Interventions
DRUGVarenicline
Tablet 1 mg BID
Tablet 1 mg BID
Sponsors
Centre for Human Drug Research, Netherlands
Amsterdam UMC, location VUmc
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Daytime sleepiness | 4 weeks | Epworth Sleepiness Scale |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fatigue | 4 weeks | Fatigue Severity Scale |
| Involuntary movements | 4 weeks | Abnormal Involuntary Movements Scale |
| Quality of life | 4 weeks | Medical Outcomes Study 36-Item Short-Form Health Survey |
| Sleep quality | 4 weeks | Pittsburgh Sleep Quality Index |
| Pharmacodynamics assessed by computerized test battery | 4 weeks | — |
| Error score | 4 weeks | Sustained Attention to Response Test |
| Sleep latency | 4 weeks | Maintenance of Wakefulness Test |
Countries
Netherlands
Outcome results
None listed