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)

Sulaiman Khadadah, R John Kimoff, Pierre Duquette, Vincent Jobin, Yves Lapierre, Andrea Benedetti, Fatema T Johara, Ann Robinson, Elaine Roger, Amit Bar-Or, Gabriel Leonard, Marta Kaminska, Daria A Trojan, Sulaiman Khadadah, R John Kimoff, Pierre Duquette, Vincent Jobin, Yves Lapierre, Andrea Benedetti, Fatema T Johara, Ann Robinson, Elaine Roger, Amit Bar-Or, Gabriel Leonard, Marta Kaminska, Daria A Trojan

Abstract

Objective: The aim of this study was to evaluate the effect of continuous positive airway pressure (CPAP) treatment on the Fatigue Severity Scale (FSS, preplanned primary outcome), another fatigue measure, sleep quality, somnolence, pain, disability, and quality of life in multiple sclerosis (MS) patients with obstructive sleep apnea-hypopnea (OSAH).

Methods: In a randomized, double-blind trial (NCT01746342), MS patients with fatigue, poor subjective sleep quality, and OSAH (apnea-hypopnea index of ⩾ 15 events per hour/sleep), but without severe OSAH (apnea-hypopnea index > 30, and 4% oxygen desaturation index > 15 events/hour or severe somnolence), were randomized to fixed CPAP or sham CPAP for 6 months. Outcome assessments were performed at 3 and 6 months.

Results: Of 49 randomized patients, 34 completed the protocol. Among completers, FSS did not improve with CPAP compared to sham at 6 months. FSS tended to improve (p = 0.09), and sleepiness (Epworth Sleepiness Scale) improved significantly (p = 0.03) at 3 months with CPAP compared to sham, but there were no other improvements with CPAP at either study evaluation.

Conclusion: In non-severe OSAH patients, CPAP did not significantly improve the primary outcome of FSS change at 6 months. In secondary analyses, we found a trend to improved FSS, and a significant reduction in somnolence with CPAP at 3 months.

Keywords: Multiple sclerosis; clinical trial; continuous positive airway pressure; fatigue; obstructive; sleep; sleep apnea; sleepiness.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: S.K., P.D., Y.L., A.B., F.T.J., A.R., E.R., A.B.-O., and G.L. have nothing to disclose. R.J.K. receives operating research support from the Multiple Sclerosis Society of Canada and the Canadian Institutes of Health Research, Fonds de Recherche du Québec-Santé, and in-kind research support from VitalAire and Philips Respironics. V.J. declares that the Sleep Laboratory where he works has received non-restrictive research grants from Biron and Pradair Laboratories. M.K. reports consulting and Advisory Committee membership at Biron Soins du Sommeil, in-kind research support from ResMed Corp and Fisher Paykel, and research support from the Canadian Institute of Health Research and Weston Institute. D.A.T. receives operating research support from the Multiple Sclerosis Society of Canada and in-kind research support from VitalAire and Philips Respironics.

Figures

Figure 1.
Figure 1.
Study protocol. The figure outlines study procedures and visits from screening to study end at 6 months of treatment. Gray boxes indicate events and visit post-randomization relevant for both active and sham CPAP groups. Compliance with study CPAP machine was evaluated for both groups during the 6-month treatment phase of the study. ESS: Epworth Sleepiness Scale; PSG: polysomnography; AHI: apnea-hyponea index; ODI: oxygen desaturation index.
Figure 2.
Figure 2.
CONSORT flow diagram. Of the 466 patients approached for the study, 49 were randomized, 34 (17 in each group) completed the study protocol and were included in the primary study analysis. PSQI: Pittsburgh Sleep Quality Index; FSS: Fatigue Severity Scale; MoCA: Montreal Cognitive Assessment; AHI: apnea-hypopnea index.

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