CPAP to Treat Cognitive Dysfunction in MS

Sponsor

University of Michigan (Other)

Overall Status

Completed

CT.gov ID

NCT02544373

Collaborator

National Multiple Sclerosis Society (Other)

134

Enrollment

Location

Arms

67.4

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The objectives of this study are to determine the effects of obstructive sleep apnea (OSA) on cognitive function in patients with multiple sclerosis (MS); and to evaluate whether OSA treatment with positive airway pressure therapy could improve cognitive dysfunction in MS patients who have OSA.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis	Device: PAP therapy	N/A

Detailed Description

Up to 70% of patients with MS suffer from cognitive dysfunction (difficulties with thinking, information processing, verbal expression, or memory). Cognitive dysfunction is one of the most disabling symptoms of MS, that can profoundly affect job performance, family responsibilities, and quality of life. While no treatments have been shown to improve cognitive dysfunction in MS, many patients have not been evaluated or treated for other common health problems that could be contributing to their cognitive dysfunction.

Up to 50% of MS patients also suffer from obstructive sleep apnea (OSA). Obstructive sleep apnea is a common disorder in which the upper airway collapses during sleep, causing poor sleep quality and decreased oxygen levels in the blood. In patients without MS, OSA is a well-established cause of poor cognitive performance. Recent studies of non-MS patients also suggest that cognitive performance may improve with OSA treatment. Yet, despite the high number of MS patients with OSA, the relationship between OSA and cognitive performance, and the effects of OSA treatment on cognitive performance in MS, has not received sufficient study.

Interested participants with MS who screen positive on a commonly used screening tool used to detect those at high risk for OSA will be invited to participate. Consenting participants will have a baseline cognitive (memory and thinking) test to assess their cognitive function, and an overnight sleep study (polysomnogram, or PSG) to determine if they have obstructive sleep apnea. If the sleep study shows signs of sleep apnea, participants will be assigned treatment for their sleep apnea with positive airway pressure (PAP) therapy, either immediately (Group 1), or 3 months after the baseline sleep study (Group 2). Groups will be assigned at random (like flipping a coin). There is a 2/3 chance that participants will be assigned to Group 1. PAP therapy is considered standard clinical care for OSA. It involves wearing an apparatus that includes a hose and a mask (that covers the nose, or nose and mouth), connected to a small machine that blows air into the airway during sleep. In order to determine which airway pressure most effectively treats an individual's sleep apnea, and what type of mask is needed, a separate sleep study known as an overnight "PAP titration study" will also be performed. This study is similar to a PSG but also involves fitting of various masks which are then hooked up to the individual and PAP machine to test the effectiveness of various PAP settings, and to determine which mask is most tolerable for the individual.

Participants will also receive repeat cognitive testing at 3 months to see if the immediate sleep apnea treatment group (Group 1) shows improvements memory and thinking, as compared to the standard care treatment group (Group 2), who will not start apnea treatment until after their repeat cognitive test. Participants will be compensated for their travel and time throughout the course of the study.

Study Design

Study Type:

Interventional

Actual Enrollment :

134 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

A Randomized Trial of Positive Airway Pressure Therapy to Treat Cognitive Dysfunction in MS Patients With Obstructive Sleep Apnea

Actual Study Start Date :

Nov 12, 2015

Actual Primary Completion Date :

Jun 25, 2021

Actual Study Completion Date :

Jun 25, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Immediate PAP therapy (Group 1) Subjects will receive PAP treatment for OSA as soon as possible after baseline PSG and repeat baseline cognitive testing 3 months after initiation of PAP therapy. PAP therapy is considered standard clinical care for OSA. It involves wearing an apparatus that includes a hose and a mask (that covers the nose, or nose and mouth), connected to a small machine that blows air into the airway during sleep. The degree of air pressure given depends on your apnea severity, and the supplied air pressure can be continuous or change with your breathing pattern (bilevel).	Device: PAP therapy Positive airway pressure treatment for obstructive sleep apnea Other Names: Positive airway pressure CPAP BiPAP Continuous positive airway pressure Bi-level positive airway pressure
Other: Standard Care PAP therapy (Group 2) Subjects will delay PAP treatment for 3 months following their baseline sleep study, and repeat their baseline cognitive testing prior to PAP treatment for sleep apnea. PAP therapy is considered standard clinical care for OSA. It involves wearing an apparatus that includes a hose and a mask (that covers the nose, or nose and mouth), connected to a small machine that blows air into the airway during sleep. The degree of air pressure given depends on your apnea severity, and the supplied air pressure can be continuous or change with your breathing pattern (bilevel).	Device: PAP therapy Positive airway pressure treatment for obstructive sleep apnea Other Names: Positive airway pressure CPAP BiPAP Continuous positive airway pressure Bi-level positive airway pressure

Arm

Intervention/Treatment

Active Comparator: Immediate PAP therapy (Group 1)

Subjects will receive PAP treatment for OSA as soon as possible after baseline PSG and repeat baseline cognitive testing 3 months after initiation of PAP therapy. PAP therapy is considered standard clinical care for OSA. It involves wearing an apparatus that includes a hose and a mask (that covers the nose, or nose and mouth), connected to a small machine that blows air into the airway during sleep. The degree of air pressure given depends on your apnea severity, and the supplied air pressure can be continuous or change with your breathing pattern (bilevel).

Device: PAP therapy

Positive airway pressure treatment for obstructive sleep apnea

Other Names:

Positive airway pressure

CPAP

BiPAP

Continuous positive airway pressure

Bi-level positive airway pressure

Other: Standard Care PAP therapy (Group 2)

Subjects will delay PAP treatment for 3 months following their baseline sleep study, and repeat their baseline cognitive testing prior to PAP treatment for sleep apnea. PAP therapy is considered standard clinical care for OSA. It involves wearing an apparatus that includes a hose and a mask (that covers the nose, or nose and mouth), connected to a small machine that blows air into the airway during sleep. The degree of air pressure given depends on your apnea severity, and the supplied air pressure can be continuous or change with your breathing pattern (bilevel).

Device: PAP therapy

Positive airway pressure treatment for obstructive sleep apnea

Other Names:

Positive airway pressure

CPAP

BiPAP

Continuous positive airway pressure

Bi-level positive airway pressure

Outcome Measures

Primary Outcome Measures

Association between OSA severity (number of apneic events per hour of sleep) and baseline performance on the Minimal Assessment of Cognitive Function in MS battery (MACFIMS) [3 weeks]
Change from baseline in performance on the Minimal Assessment of Cognitive Function in MS battery (MACFIMS) [3 months]
Mean change in scores on individual MACFIMS tests from baseline to month 3 cognitive testing

Other Outcome Measures

Association between polysomnographic measures of sleep efficiency (ratio of time spent asleep to total time in bed) and baseline performance on the Minimal Assessment of Cognitive Function in MS battery (MACFIMS) [3 weeks]
Association between wake time after sleep onset (total time in minutes spent awake after sleep onset, and before final awakening time) and baseline performance on the Minimal Assessment of Cognitive Function in MS battery (MACFIMS) [3 weeks]
Association between the total arousal index (average number of EEG arousals per hour of sleep) and baseline performance on the Minimal Assessment of Cognitive Function in MS battery (MACFIMS) [3 weeks]
Association between sleep stage percentages (% total sleep time spent in stage N1, N2, N3, and REM sleep) and baseline performance on the Minimal Assessment of Cognitive Function in MS battery (MACFIMS) [3 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Age of 18-70 years at screening
Diagnosis of clinically definite MS
Willingness to undergo in-lab baseline polysomnography (PSG) and positive airway pressure (PAP) titration (if needed)
Willingness to undergo 2 separate 90-minute cognitive testing sessions
Either one of the following:

Score of >=2 sleep apnea risk factors on the "STOP-Bang" sleep apnea screening questionnaire. The STOP-Bang questionnaire is a screening tool consisting of eight items which reflect OSA risk factors. STOP-Bang scores of ≥3 indicate elevated risk for moderate-severe OSA in the general population, and scores as low as 2 are frequently seen in MS patients with OSA, based on previous data from the PI).

Have a pre-existing diagnosis of OSA based on a previous overnight sleep study (either home study or in-lab) but have not yet started using PAP therapy on a compliant basis. *If OSA was NOT diagnosed by a U-M in-lab sleep study within the past year prior to screening, subjects must be willing to get new baseline in-lab U-M PSG as part of study.

Willingness to start treatment with PAP if OSA present

Exclusion Criteria

Physical, psychiatric or cognitive impairment that prevents informed consent, PSG, PAP use, or reliable longitudinal follow-up
Cardiopulmonary conditions that may increase sleep apnea risk
Current treatment, such as PAP, for obstructive or central sleep apnea
History of surgical treatment for OSA
Nervous system diseases other than MS that may predispose subjects to OSA (such as Parkinson's disease, amyotrophic lateral sclerosis, or recent stroke)
History of concomitant central nervous system disease that could influence cognition, such as large vessel territory stroke, Alzheimer's disease, Parkinson's disease, or Lewy body dementia
Concomitant systemic autoimmune disease with secondary central nervous system involvement (including CNS lupus or neurosarcoidosis).
Pregnancy
Evidence of clinical MS relapse within the last 30 days prior to enrollment
Systemic high dose steroid use (1 gram IV methylprednisolone daily for 3-5 days or equivalent)for an MS relapse within the last 30 days prior to enrollment
Unwillingness to initiate PAP therapy if clinically indicated
Severe depression at screening per the Patient Health Questionnaire-8 (PHQ-8) (The PHQ-8 is a brief, self-administered questionnaire that evaluates core symptoms associated with major depressive disorder. Scores range from 0 to 24 based on the frequency and severity of depressive symptoms over the previous two weeks.)
Anticipated initiation, dosage change, or discontinuation in medications that could, per the opinion of the investigators, influence cognitive test scores from baseline to follow-up, including MS disease modifying therapies, hypnotic agents, narcotic-based medications, benzodiazepines, antispasmodics, or 4-aminopyridine
ESS scores >= 16 on baseline visit
Subjects with extreme OSA accompanied by signs of cardiopulmonary compromise (RDI>60 respiratory events per hour with severe nocturnal hypoxia or unstable ECG rhythms on PSG), will be excluded unless they are randomized to immediate PAP arm
Any other condition or treatment that in the opinion of the investigator could affect subject safety or study eligibility