A randomized, subject and rater-blinded, placebo-controlled trial of dimethyl fumarate for obstructive sleep apnea.

Abstract

Study Objectives:

To investigate the therapeutic effect of dimethyl fumarate (DMF, an immunomodulatory agent) on obstructive sleep apnea (OSA), and potential influence of any such effect by selected proinflammatory molecules.

Methods:

Patients with OSA who deferred positive airway pressure therapy were randomized (2:1) to receive DMF or placebo for 4 months. Participants underwent polysomnography before randomization and at 4 months. Blood was collected monthly. The primary outcome was the mean group change in respiratory disturbance index (δ-RDI). Secondary analyses focused on the association between treatment effect of DMF (on RDI) and expression of plasma cytokines and chemokines, or nuclear factor κ-B (NFκB) signaling molecules in peripheral blood mononuclear cells.

Results:

N = 65 participants were randomized. N = 50 participants (DMF = 35, placebo = 15) had complete data for final analyses. The mean difference in δ-RDI between groups was 13.3 respiratory events/hour of sleep: -3.1+/-12.9 vs. 10.2+/-13.1 in DMF and placebo groups, respectively (mixed-effects model treatment effect: β = -0.14, SE = 0.062, p = 0.033). Plasma levels of TNF-α showed only nonsignificant decreases, and IL-10 and IL-13 only nonsignificant increases, in DMF-treated participants compared with placebo. No significant interaction or main effect on RDI for selected cytokines and chemokines was found. Participants with a therapeutic response to DMF did experience significant reductions in intracellular NFκB signaling molecules at 4 months. Overall, DMF was well-tolerated.

Conclusions:

The immunomodulatory drug DMF partially ameliorates OSA severity. Suppression of systemic inflammation through reduction of NFκB signaling may mediate this effect.

Clinical Trials:

ClinicalTrials.gov, NCT02438137, https://clinicaltrials.gov/ct2/show/NCT02438137?term=NCT02438137&rank=1.

• Authors: Tiffany J Braley, Amanda K Huber, Benjamin M Segal, Neeraj Kaplish, Rachel Saban, Jesse M Washnock-Schmid, Ronald D Chervin
• Journal: Sleep (Sleep) Vol. 41 Issue 8 (08 01 2018) ISSN: 1550-9109 [Electronic] United States
• PMID: 29800466 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Immunosuppressive Agents
• Placebos
• Dimethyl Fumarate

Topics

• Adolescent
• Adult
• Aged
• Dimethyl Fumarate (therapeutic use)
• Female
• Humans
• Immunosuppressive Agents (therapeutic use)
• Leukocytes, Mononuclear
• Male
• Middle Aged
• Placebos (therapeutic use)
• Polysomnography
• Sleep (drug effects, physiology)
• Sleep Apnea, Obstructive (complications, drug therapy)
• Young Adult