CPAP to Treat Cognitive Dysfunction in MS
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| ClinicalTrials.gov Identifier: NCT02544373 |
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Recruitment Status :
Completed
First Posted : September 9, 2015
Results First Posted : September 14, 2022
Last Update Posted : September 14, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Multiple Sclerosis | Device: PAP therapy | Not Applicable |
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.
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 also have OSA.
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 Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 135 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 : | November 12, 2015 |
| Actual Primary Completion Date : | June 25, 2021 |
| Actual Study Completion Date : | June 25, 2021 |
| Arm | Intervention/treatment |
|---|---|
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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).
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Device: PAP therapy
Positive airway pressure treatment for obstructive sleep apnea
Other Names:
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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).
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Device: PAP therapy
Positive airway pressure treatment for obstructive sleep apnea
Other Names:
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- Association Between Obstructive Sleep Apnea (OSA) Severity [as Measured by Apnea Hypopnea Index (AHI) e.g., Number of Apneic Events Per Hour of Sleep] and Baseline Performance on the Minimal Assessment of Cognitive Function in MS Battery (MACFIMS) [ Time Frame: Participants had up to 3 weeks to complete both baseline cognitive testing and PSG ]
Bivariate associations between AHI measured with PSG, and baseline MACFIMS test results which include:
- Controlled Oral Word Association Test (COWAT): verbal fluency;
- Judgement of Line Orientation test (JLO): visuospatial perception;
- Brief Visuospatial Memory Test Revised Total (BVMT-R Total) and Brief Visuospatial Memory Test Revised Delayed (BVMT-R Delayed): visual memory & learning;
- California Verbal Learning Test-II Total score (CVLT-II): verbal memory & learning;
- Paced Auditory Serial Addition Test-2 (PASAT-2), Paced Auditory Serial Addition Test-3 (PASAT-3) and Symbol Digit Modalities test (SDMT): memory, attention, processing speed.
For each test higher scores indicate better cognitive performance. Beta coefficients were generated with multiple linear regression models, yielding the confidence intervals shown below.
- Change From Baseline in Performance on the Minimal Assessment of Cognitive Function in MS Battery (MACFIMS) [ Time Frame: baseline, 3 months ]
Mean change in scores on individual MACFIMS tests from baseline to month 3 cognitive testing, as calculated by Month 3 minus baseline score shown by treatment group. MACFIMS tests with score ranges (minimum-maximum) are listed here:
- Controlled Oral Word Association Test (COWAT) 0 - no recognized upper limit;
- Judgement of Line Orientation test (JLO) 0-34 based on scores adjusted for age and sex;
- Brief Visuospatial Memory Test Revised Total (BVMT-R Total) 0-36;
- Brief Visuospatial Memory Test Revised Delayed (BVMT-R Delayed), 0-12;
- California Verbal Learning Test-II Total score (CVLT-II); (T scores necessary for analysis; 50=population mean; 10=SD);
- Paced Auditory Serial Addition Test-2 (PASAT-2), 0-60;
- Paced Auditory Serial Addition Test-3 (PASAT-3) 0-60; and
- Symbol Digit Modalities test (SDMT) 0-110. For all measures, higher scores mean better performance, so based on subtracting 3 month values minus baseline, any positive numbers indicate improvement.
- 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 3 weeks ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 70 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
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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).
OR
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02544373
| United States, Michigan | |
| University of Michigan Medical Center | |
| Ann Arbor, Michigan, United States, 48109 | |
| Principal Investigator: | Tiffany Braley, MD, MS | University of Michigan |
Documents provided by Tiffany J. Braley, MD, MS, University of Michigan:
| Responsible Party: | Tiffany J. Braley, MD, MS, Associate Professor, Neurology, University of Michigan |
| ClinicalTrials.gov Identifier: | NCT02544373 |
| Other Study ID Numbers: |
HUM00098738 |
| First Posted: | September 9, 2015 Key Record Dates |
| Results First Posted: | September 14, 2022 |
| Last Update Posted: | September 14, 2022 |
| Last Verified: | August 2022 |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | Yes |
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OSA Obstructive Sleep Apnea Cognition Cognitive Dysfunction |
Memory Positive Aiway Pressure CPAP MS |
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Multiple Sclerosis Cognitive Dysfunction Demyelinating Autoimmune Diseases, CNS Autoimmune Diseases of the Nervous System Nervous System Diseases Demyelinating Diseases |
Autoimmune Diseases Immune System Diseases Cognition Disorders Neurocognitive Disorders Mental Disorders |