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

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 (delta-RDI). Secondary analyses focused on the association between treatment effect of DMF (on RDI) and expression of plasma cytokines and chemokines, or nuclear factor kappa-B (NF kappa B) 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 d-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: beta = -0.14, SE = 0.062, p = 0.033). Plasma levels of TNF-alpha 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 NF kappa B 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 NF kappa B signaling may mediate this effect.