TAP: Cognitive Benefits of Treating Sleep Apnea in Parkinson's Disease

• Sponsor: University of California, San Diego (Other)
• Overall Status: Completed
• CT.gov ID: NCT00492115
• Collaborator: National Institute on Aging (NIA) (NIH)
• Enrollment: 98
• Location: 1
• Arms: 2
• Duration (Months): 70
• Patients Per Site Per Month: 1.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Parkinson's Disease; Sleep Disordered Breathing	Device: Continuous positive airway pressure (CPAP); Device: Placebo CPAP	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 98 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Cognitive Benefits of Treating Sleep Apnea in Dementia
• Study Start Date: Jul 1, 2007
• Actual Primary Completion Date: May 1, 2013
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: therapeutic CPAP Treatment (6 weeks)" Intervention - The active comparator is an intervention of nightly therapeutic CPAP (continuous positive airway pressure) treatment for 6 weeks. Patients will use CPAP every night for the full duration of the study, i.e., 6 weeks	Device: Continuous positive airway pressure (CPAP); therapeutic Continuous positive airway pressure (tCPAP) nightly for 6 weeks
Placebo Comparator: Sham CPAP/therapetuic CPAP (6 weeks)" The placebo comparator is an intervention of placebo CPAP (continuous positive airway pressure) nightly for 3 weeks followed by therapeutic CPAP treatment nightly for 3 weeks. Patients will use a sham CPAP (no real pressure) for 3 weeks and then will be switched to real CPAP for 3 weeks.	Device: Placebo CPAP; Ineffective Continuous positive airway pressure (pCPAP) for 3 weeks followed by therapeutic CPAP for 3 weeks

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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%.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSD	San Diego	California	United States	92093

Sponsors and Collaborators

• University of California, San Diego
• National Institute on Aging (NIA)

Investigators

• Principal Investigator: Sonia Ancoli-Israel, PhD, University of California, San Diego

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sonia Ancoli-Israel, Professor, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT00492115
• Other Study ID Numbers: AG08415; R01AG008415
• First Posted: Jun 27, 2007
• Last Update Posted: Jul 23, 2019
• Last Verified: Jul 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Sonia Ancoli-Israel, Professor, University of California, San Diego: sleep; dementia; apnea; memory; Parkinson's disease
• Additional relevant MeSH terms: Sleep Apnea Syndromes; Parkinson Disease

Study Results

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 Detail	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

Arm/Group Title	A: Continuous Positive Airway Pressure (CPAP)	B: Placebo Continuous Positive Airway Pressure
Arm/Group Description	Continuous positive airway pressure (CPAP) Continuous positive airway pressure (CPAP): therapeutic CPAP for six weeks	Placebo Continuous Positive airway pressure Placebo CPAP: Ineffective CPAP 3 weeks placebo CPAP followed by 3 weeks of therapeutic CPAP
Period Title: Overall Study
STARTED	19	19
COMPLETED	16	15
NOT COMPLETED	3	4

Baseline Characteristics

Arm/Group Title	A: Continuous Positive Airway Pressure	B. Sham CPAP	Total
Arm/Group Description	Continuous Positive Airway Pressure (therapeutic CPAP) for 6 weeks	Sham (placebo) CPAP for 3 weeks followed by therapeutic CPAP for 3 weeks.	Total of all reporting groups
Overall Participants	19	19	38
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.7 (8.5)	67.7 (10.0)	67.2 (9.3)
Sex: Female, Male (Count of Participants)
Female	7 36.8%	5 26.3%	12 31.6%
Male	12 63.2%	14 73.7%	26 68.4%
Region of Enrollment (participants) [Number]
United States	19 100%	19 100%	38 100%

Outcome Measures

1. Primary Outcome

Title	Tests to Determine the Apnea-hypopnea Index (Number of Apneas and Hypopneas Per Hour of Sleep)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A: Continuous Positive Airway Pressure (CPAP):	B: Placebo CPAP: Ineffective CPAP
Arm/Group Description	CPAP Continuous positive airway pressure (CPAP): therapeutic CPAP	Placebo CPAP Placebo CPAP: Ineffective CPAP
Measure Participants	17	15
Mean (Standard Deviation) [apnea hypopnea index]	5.2 (2)	20 (4)

2. Secondary Outcome

Title	Sleep Stages; %Time Spent at SaO2<90%;
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A: Continuous Positive Airway Pressure (CPAP):	B: Placebo CPAP: Ineffective CPAP
Arm/Group Description	CPAP Continuous positive airway pressure (CPAP): therapeutic CPAP	Placebo CPAP Placebo CPAP: Ineffective CPAP
Measure Participants	17	15
Mean (Standard Deviation) [Percent time spent at low oxygen <90%]	2.1 (1)	12.9 (5)

Adverse Events

Time Frame	Adverse event data were collected for the full 6 weeks per participant
Arm/Group Title	A: Continuous Positive Airway Pressure (CPAP): Therapeutic CPA		B: Placebo CPAP: Ineffective CPAP
Arm/Group Description	CPAP Continuous positive airway pressure (CPAP): therapeutic CPAP for 6 weeks		Placebo CPAP Placebo CPAP: Ineffective CPAP for 3 weeks followed by therapeutic CPAP for 3 weeks
All Cause Mortality
	A: Continuous Positive Airway Pressure (CPAP): Therapeutic CPA		B: Placebo CPAP: Ineffective CPAP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/19 (0%)
Serious Adverse Events
	A: Continuous Positive Airway Pressure (CPAP): Therapeutic CPA		B: Placebo CPAP: Ineffective CPAP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/19 (0%)
Other (Not Including Serious) Adverse Events
	A: Continuous Positive Airway Pressure (CPAP): Therapeutic CPA		B: Placebo CPAP: Ineffective CPAP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/19 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.