Parkinson's Disease, Sleep Disordered Breathing
Conditions
Keywords
sleep, dementia, apnea, memory, Parkinson's disease
Brief summary
Patients with sleep disordered breathing (SDB), also called sleep apnea, experience nighttime disrupted sleep and, because they stop breathing for short periods during the night, do not get sufficient oxygen to their brains. This can frequently result in daytime impairments including difficulties with memory. The state-of-the-art treatment for SDB is Continuous Positive Airway Pressure (CPAP). Many non-demented SDB patients who are successfully treated with CPAP show improvement in memory and other cognitive functions. Data have shown that patients with Parkinson's disease have a high rate of SDB. Patients with Parkinson's disease also often have problems with memory. This study will test the effects of treating SDB among patients with Parkinson's disease and SDB. Specifically, the study will test the effect of CPAP treatment on SDB and sleep; the effect of CPAP treatment on daytime sleepiness, cognition, overall quality of life and mood; the effect of CPAP treatment on the frequency of symptoms of REM behavior disorder and restless legs syndrome; the effect of continued CPAP use (beyond the six weeks of the study) on SDB, sleep, cognition, mood and quality of life; whether the study-partner feels that CPAP improves the patient's sleep, mood and overall functioning; whether study-partners feel that their own sleep, mood and overall functioning improve as the patient's sleep improves both during the 6-week protocol and at follow-up for those opting to continue using CPAP.
Detailed description
This study will examine the effect of three weeks vs. six weeks of CPAP treatment on cognitive functioning and sleep in patients with Parkinson's disease and sleep apnea. It is designed as a randomized, double blind, placebo-controlled trial of CPAP. As a comparison group, half the patients will first be randomly assigned to three weeks of shamCPAP, followed by three weeks of therapeutic CPAP treatment. Sleep, functional outcome and mood questionnaires and a repeatable neuropsychological test battery, chosen to be sensitive to the type of changes we expect to find in memory and cognitive function, will be administered before the start of treatment, after three weeks, and after six weeks of treatment.
Interventions
DEVICEContinuous positive airway pressure (CPAP)
therapeutic Continuous positive airway pressure (tCPAP) nightly for 6 weeks
DEVICEPlacebo CPAP
Ineffective Continuous positive airway pressure (pCPAP) for 3 weeks followed by therapeutic CPAP for 3 weeks
Sponsors
National Institute on Aging (NIA)
University of California, San Diego
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of dementia due to Parkinson's disease (according to the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (code 294.1) * MMSE score between 18 and 26, inclusive; cognitive symptoms must occur at least one year after the diagnosis of PDD * Apnea hypopnea index \>10 (i.e., 10 apneas plus hypopneas per hour of sleep) * Over the age of 50 years * Stable health * Fluent English speaking * Patients will be allowed to continue dopaminergic medications, acetylcholinesterase inhibitors, psychotropic medications, memory enhancers, health food supplements, etc. as long as they have been stable on the same dose for at least two months prior to participation and agree to continue on this dose for the duration of the 6-week study.
Exclusion criteria
* Current treatment for sleep apnea (to avoid discontinuing already established treatment for sleep apnea and any carry over confounding effect of treatment on cognition). * Central sleep apnea * Use of medications known to influence sleep (i.e. sedative hypnotics, narcotics) if the dose cannot remain stable for the duration of the study. * Bronchospastic and symptomatic chronic obstructive pulmonary disease as indicated by regular use of bronchodilators, steroids, history of carbon dioxide retention, waking hypoxemia (PaO2 \<60 mmHg or SpO2 \<92 % by pulse oximetry), or use of supplemental oxygen. * Symptomatic coronary or cerebral vascular disease (history of myocardial infarction, angina, stroke, or transient ischemic attacks), history of life-threatening arrhythmias, cardiomyopathy, or current alcohol or drug abuse * Current diagnosis of active seizure disorder; presence of any neurodegenerative disorder other than PDD or other causes of dementia * Any behavioral or physical problem that would preclude completion of the primary evaluation or treatment with CPAP.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tests to Determine the Apnea-hypopnea Index (Number of Apneas and Hypopneas Per Hour of Sleep) | six weeks | Overnight sleep studies were done to determine the effect of treatment on the apnea-hypopnea index (number of apneas and hypopneas per hour of sleep) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sleep Stages; %Time Spent at SaO2<90%; | 6 weeks | Overnight sleep studies were done to examine the effect of CPAP treatment on sleep stages and on %time spent at Sa)2\<90%. |
Countries
United States
Participant flow
Recruitment details
Patients were referred to UCSD by community neurologists or volunteered after hearing a talk about the study at PD support group meetings.
Pre-assignment details
183 contacted; 144 screened/phone; 106 consented, 5 dropped/12 excluded; 89 screened for apnea with sleep study (2 dropped during night study), 44 had no sleep apnea. 5 declined treatment. 19 participants randomized to each arm
Participants by arm
| Arm | Count |
|---|---|
| A: Continuous Positive Airway Pressure Continuous Positive Airway Pressure (therapeutic CPAP) for 6 weeks | 19 |
| B. Sham CPAP Sham (placebo) CPAP for 3 weeks followed by therapeutic CPAP for 3 weeks. | 19 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 3 | 4 |
Baseline characteristics
| Characteristic | A: Continuous Positive Airway Pressure | B. Sham CPAP | Total |
|---|---|---|---|
| Age, Continuous | 66.7 years STANDARD_DEVIATION 8.5 | 67.7 years STANDARD_DEVIATION 10 | 67.2 years STANDARD_DEVIATION 9.3 |
| Region of Enrollment United States | 19 participants | 19 participants | 38 participants |
| Sex: Female, Male Female | 7 Participants | 5 Participants | 12 Participants |
| Sex: Female, Male Male | 12 Participants | 14 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 19 |
| other Total, other adverse events | 0 / 19 | 0 / 19 |
| serious Total, serious adverse events | 0 / 19 | 0 / 19 |
Outcome results
Primary
Tests to Determine the Apnea-hypopnea Index (Number of Apneas and Hypopneas Per Hour of Sleep)
Overnight sleep studies were done to determine the effect of treatment on the apnea-hypopnea index (number of apneas and hypopneas per hour of sleep)
Time frame: six weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A: Continuous Positive Airway Pressure (CPAP): | Tests to Determine the Apnea-hypopnea Index (Number of Apneas and Hypopneas Per Hour of Sleep) | 5.2 apnea hypopnea index | Standard Deviation 2 |
| B: Placebo CPAP: Ineffective CPAP | Tests to Determine the Apnea-hypopnea Index (Number of Apneas and Hypopneas Per Hour of Sleep) | 20 apnea hypopnea index | Standard Deviation 4 |
Secondary
Sleep Stages; %Time Spent at SaO2<90%;
Overnight sleep studies were done to examine the effect of CPAP treatment on sleep stages and on %time spent at Sa)2\<90%.
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A: Continuous Positive Airway Pressure (CPAP): | Sleep Stages; %Time Spent at SaO2<90%; | 2.1 Percent time spent at low oxygen <90% | Standard Deviation 1 |
| B: Placebo CPAP: Ineffective CPAP | Sleep Stages; %Time Spent at SaO2<90%; | 12.9 Percent time spent at low oxygen <90% | Standard Deviation 5 |