Effect of Long-acting Levodopa on Obstructive Sleep Apnea in Parkinson's Disease

Study Overview
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Brief Summary
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This trial will assess whether long-acting levodopa taken at night improves obstructive sleep apnea (OSA) in patients with Parkinson's disease (PD), as compared with placebo.

Detailed Description
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Participants with Parkinson's disease and sleep apnea will take long-acting levodopa and placebo at bedtime for 2 weeks each, in a randomized order, with a 2-week washout period in-between. Sleep studies will be done at the end of each period. The primary outcome will be the apnea-hypopnea index change from baseline to on-medication, comparing active medication to placebo. Other outcomes will include other polysomnographic parameters such as oxygenation measures and sleep architecture variables, as well as the Epworth Sleepiness Scale, the Montreal Cognitive Assessment, the Parkinson's disease sleep scale and the Unified Parkinson's Disease Rating Scale. Adverse events will be closely monitored.

Official Title
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Effect of Long-acting Levodopa on Obstructive Sleep Apnea in Parkinson's Disease

Conditions
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Parkinson's Disease, Obstructive Sleep Apnea

Intervention / Treatment
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* Drug: Sinemet CR
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of idiopathic PD consistent with the UK Brain Bank; Presence of OSA on screening PSG, as defined by an AHI ≥ 15/h (moderate to severe OSA); Stable regimen of anti-PD medication for 4 weeks prior to entry into the study, and no planned change during the study Exclusion Criteria: Other major neurological disorder; Already taking long-acting levodopa (at any time of day); Taking short-acting levodopa at bedtime or during the night; Any contraindication to long-acting levodopa (see below); Severe levodopa induced dyskinesias; Already on or requiring treatment for restless legs syndrome ; Body mass index >35 kg/m2; Intercurrent upper respiratory tract infection; Other known cause of OSA (e.g. craniofacial malformation); Active treatment of OSA (CPAP, dental appliance or other), unless willing to stop treatment 2 weeks prior to start and during the duration of the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A (drug-placebo)<br>Sinemet CR (Long-acting levodopa: levodopa 200mg/ carbidopa 50mg) followed by a washout period and placebo oral capsule, each taken at bedtime for 2 weeks | Drug: Sinemet CR<br>* Capsule 250 mg / 50 mg taken at bedtime<br>* Other names: Long acting levodopa;Drug: Placebo oral capsule<br>* Capsule taken at bedtime<br>* Other names: Placebo;|
| Experimental: B (placebo-drug)<br>Placebo oral capsule followed by a washout period and Sinemet CR (Long-acting levodopa: levodopa 200mg/ carbidopa 50mg), taken at bedtime for 2 weeks | Drug: Sinemet CR<br>* Capsule 250 mg / 50 mg taken at bedtime<br>* Other names: Long acting levodopa;Drug: Placebo oral capsule<br>* Capsule taken at bedtime<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apnea-hypopnea index (AHI) |  | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients having adverse events leading to discontinuation of drug (Feasibility and tolerability) | Proportion of patients having adverse events leading to discontinuation of drug | 2 weeks | 
| Oxygenation from polysomnography | oxygen desaturation index | 2 weeks | 
| Oxygenation from polysomnography | mean oxygen saturation | 2 weeks | 
| Oxygenation from polysomnography | time with saturation below 90% | 2 weeks | 
| Objective sleep quality from polysomnography | Sleep efficiency | 2 weeks | 
| Objective sleep quality from polysomnography | total sleep time | 2 weeks | 
| Objective sleep quality from polysomnography | wake after sleep onset | 2 weeks | 
| Objective sleep quality from polysomnography | sleep stages distribution | 2 weeks | 
| Objective sleep quality from polysomnography | arousal index | 2 weeks | 
| Subjective sleep quality | Parkinson's Disease Sleep Scale-R | 2 weeks | 
| Daytime sleepiness | Epworth Sleepiness Scale | 2 weeks | 
| Non-motor symptoms | MDS-UPDRS part I | 2 weeks | 
| Cognitive function | Montreal Cognitive Assessment (MoCA) | 2 weeks |