Clinical trial NCT02473562: Varenicline Treatment for Excessive Daytime Sleepiness in Parkinson's Disease
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Parkinson's Disease
Keywords: Parkinson's disease
Varenicline
Excessive daytime sleepiness
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
Collaborators: name: Centre for Human Drug Research, Netherlands
First posted: 2015-06-16
Enrollment: 22
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Daytime sleepiness
timeFrame: 4 weeks
Secondary outcomes:
measure: Sleep quality
timeFrame: 4 weeks
measure: Fatigue
timeFrame: 4 weeks
measure: Involuntary movements
timeFrame: 4 weeks
measure: Quality of life
timeFrame: 4 weeks
measure: Sleep latency
timeFrame: 4 weeks
measure: Pharmacodynamics assessed by computerized test battery
timeFrame: 4 weeks
measure: Error score
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
city: Amsterdam
country: Netherlands
facility: VU university medical center
Study officials:
affiliation: VU University Medical Center, depart. of neurology
name: Elisabeth Foncke, PhD, MD
role: STUDY_CHAIR
affiliation: VU University Medical Center, depart. of neurology
name: Bernard Uitdehaag, Phd, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: VU University Medical Center, depart. of neurology
name: Tom van Mierlo, MD
role: STUDY_DIRECTOR
References: