Sleep Apnea in Multiple Sclerosis Positive Airway Pressure Trial (SAMSPAP)

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

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.

Study Overview

• Status: Completed
• Conditions: Obstructive Sleep Apnea-hypopnea in Multiple Sclerosis Patients
• Intervention / Treatment: Device: Effective continuous positive airway pressure (CPAP); Device: Sham continuous positive airway pressure (CPAP)

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
      • McGill University Health Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: McGill University
• Collaborators: Centre hospitalier de l'Université de Montréal (CHUM); Philips Respironics; Multiple Sclerosis Society of Canada (Primary funding agency); VitalAire Incorporated (Respiratory Therapist time)
• Investigators: Principal Investigator: John Kimoff, MD, McGill University; Principal Investigator: Daria Trojan, MD, McGill University

Publications and helpful links

General Publications

• Khadadah S, Kimoff RJ, Duquette P, Jobin V, Lapierre Y, Benedetti A, Johara FT, Robinson A, Roger E, Bar-Or A, Leonard G, Kaminska M, Trojan DA. Effect of continuous positive airway pressure treatment of obstructive sleep apnea-hypopnea in multiple sclerosis: A randomized, double-blind, placebo-controlled trial (SAMS-PAP study). Mult Scler. 2022 Jan;28(1):82-92. doi: 10.1177/13524585211010390. Epub 2021 Apr 23.

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): November 30, 2018
• Study Completion (Actual): November 30, 2018

Study Registration Dates

• First Submitted: December 6, 2012
• First Submitted That Met QC Criteria: December 7, 2012
• First Posted (Estimate): December 10, 2012

Study Record Updates

• Last Update Posted (Actual): January 11, 2019
• Last Update Submitted That Met QC Criteria: January 10, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Respiratory Tract Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Multiple Sclerosis; Sclerosis; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea
• Other Study ID Numbers: MSSC-G004