Varenicline Treatment for Excessive Daytime Sleepiness in Parkinson's Disease

Phase 4

Terminated

• Conditions: Parkinson's Disease
• Interventions: Drug: Placebo (for varenicline); Drug: Varenicline

• Registration Number: NCT02473562
• Lead Sponsor: Amsterdam UMC, location VUmc

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.

Study Timeline

• Study Start: 2013-05
• Study First Submitted: 2015-06-12
• Study First Submitted QC: 2015-06-15
• Study First Posted: 2015-06-16
• Primary Completion: 2018-01
• Study Completion: 2018-01
• Status Verified: 2018-10
• Last Update Submitted: 2018-10-04
• Last Update Posted: 2018-10-09

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 22

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo (for varenicline)	Placebo capsule
Varenicline	Varenicline	Varenicline capsule 1 mg BID

Primary Outcome Measures

Name	Time	Method
Daytime sleepiness	4 weeks	Epworth Sleepiness Scale

Secondary Outcome Measures

Name	Time	Method
Sleep quality	4 weeks	Pittsburgh Sleep Quality Index
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 latency	4 weeks	Maintenance of Wakefulness Test
Pharmacodynamics assessed by computerized test battery	4 weeks
Error score	4 weeks	Sustained Attention to Response Test

Trial Locations

Locations (2)

VU university medical center; 🇳🇱 Amsterdam, Netherlands

Academic Medical Center; 🇳🇱 Amsterdam, Netherlands