Sleep Apnea in Multiple Sclerosis Positive Airway Pressure Trial

Study Overview
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Brief Summary
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Fatigue is highly prevalent among multiple sclerosis (MS) patients and has pervasive adverse effects on daily functioning and quality of life. The investigators found in a recent study that obstructive sleep apnea-hypopnea (OSAH) is the most common sleep abnormality in multiple sclerosis (MS) patients. There was also a significant relationship between OSAH and higher fatigue scores in MS patients. Preliminary work from the investigators in this group of subjects shows that treatment of sleep disorders (mostly OSAH) can improve fatigue and other symptoms in some MS patients. However, it is now necessary to systemically test the effect of OSAH treatment in a randomized, controlled study, to be sure that it really does improve fatigue and other symptoms. The best treatment for OSAH in the general population is continuous positive airway pressure (CPAP). This treatment has been well tolerated by most MS patients who have used the device at the investigators' center. This project will therefore be a randomized, controlled, clinical trial of CPAP in MS patients with OSAH. The effects of six months of CPAP treatment on fatigue as well as sleep quality, somnolence, pain, disability, and quality of life will be studied.

Official Title
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A Randomized, Controlled, Clinical Trial of Continuous Positive Airway Pressure Treatment of Obstructive Sleep Apnea-Hypopnea in Multiple Sclerosis

Conditions
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Obstructive Sleep Apnea-hypopnea in Multiple Sclerosis Patients

Intervention / Treatment
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* Device: Effective continuous positive airway pressure (CPAP)
* Device: Sham continuous positive airway pressure (CPAP)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of multiple sclerosis by a neurologist based on standard criteria (Annals Neurol 2011; 69:292-302) Expanded Disability Status Scale score of 0 to 7.0 MS-relapse free for >30 days prior to screening Pittsburgh sleep quality Index > 5 Fatigue Severity Scale score >=4 Montreal Cognitive Assessment (MoCA) >= 26 diagnosis of OSAH by polysomnography showing AHI >= 15 events/h of sleep forced vital capacity >60% predicted Exclusion Criteria: pregnancy or planned pregnancy psychiatric conditions which could preclude compliance with informed consent, study procedures, or study requirements other significant neurological, pulmonary, otorhinological, and medical disorders major depression within the past year any value of >1.5 times the upper limit or <0.75 the lower limit of the reference range for any standard clinical hemogram and biochemistry determinations which is clinically significant current treatment for OSAH presence of another untreated sleep disorder which is clinically significant very severe OSAH (safety criterion)defined as an AHI >30 with either a 4% O2 desaturation index >15 events/h OR work in a safety-critical position OR an ESS score >=15

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: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Effective CPAP<br>Continuous positive airway pressure: effective fixed level determined by polysomnographic titration | Device: Effective continuous positive airway pressure (CPAP)<br> <br> |
| Sham Comparator: Sham CPAP<br>Continuous positive airway pressure device modified by manufacturer to deliver minimal pressure | Device: Sham continuous positive airway pressure (CPAP)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fatigue Severity Scale |  | Six months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fatigue Scale for Motor and Cognitive Functions |  | Three & Six months | 
| Epworth Sleepiness Scale |  | Three & Six months | 
| Pittsburgh Sleep Quality Index |  | Three & Six months | 
| Pain visual analog scale |  | Three & Six months | 
| Multiple Sclerosis-specific quality of life measure-54 (MSQOL-54) |  | Three & Six months | 
| Fatigue Severity Scale | Primary outcome measure is FSS at six months | Three months | 
| Expanded Disability Status Scale | Standard scale for evaluation of Multiple Sclerosis-related disease disability | Three & Six months | 
| Center for Epidemiological Studies-Depression Scale |  | Three & Six months | 
| Cognitive evaluation | Montreal Cognitive Assessment (MoCA) and Tower of London-Drexel University | Six months | 
| Polysomnographic variables | Standard complete polysomnographic measures of sleep and respiration | Six months | 
| Objective CPAP compliance | Standard measures of CPAP use and efficacy from machine microprocessor | Three and Six Months |