Dimethyl Fumarate for Obstructive Sleep Apnea

Summary

The overall purpose of this study is to determine whether the oral medication dimethyl fumarate is an effective treatment for obstructive sleep apnea in patients who are unable, unwilling, or uneager to use positive airway pressure therapy.

Timeline

Start

2015-05

Primary completion

2016-04

Completion

2016-05

Publications

• Background Aloia MS, Stanchina M, Arnedt JT, Malhotra A, Millman RP. Treatment adherence and outcomes in flexible vs standard continuous positive airway pressure therapy. Chest. 2005 Jun;127(6):2085-93. doi: 10.1378/chest.127.6.2085.
• Background Vgontzas AN, Bixler EO, Tan TL, Kantner D, Martin LF, Kales A. Obesity without sleep apnea is associated with daytime sleepiness. Arch Intern Med. 1998 Jun 22;158(12):1333-7. doi: 10.1001/archinte.158.12.1333.
• Background Vgontzas AN, Zoumakis E, Lin HM, Bixler EO, Trakada G, Chrousos GP. Marked decrease in sleepiness in patients with sleep apnea by etanercept, a tumor necrosis factor-alpha antagonist. J Clin Endocrinol Metab. 2004 Sep;89(9):4409-13. doi: 10.1210/jc.2003-031929.
• Background Thomas KS, Motivala S, Olmstead R, Irwin MR. Sleep depth and fatigue: role of cellular inflammatory activation. Brain Behav Immun. 2011 Jan;25(1):53-8. doi: 10.1016/j.bbi.2010.07.245. Epub 2010 Jul 23.
• Background Aihara K, Oga T, Chihara Y, Harada Y, Tanizawa K, Handa T, Hitomi T, Uno K, Mishima M, Chin K. Analysis of systemic and airway inflammation in obstructive sleep apnea. Sleep Breath. 2013 May;17(2):597-604. doi: 10.1007/s11325-012-0726-y. Epub 2012 Jun 7.
• Background Tam CS, Wong M, McBain R, Bailey S, Waters KA. Inflammatory measures in children with obstructive sleep apnoea. J Paediatr Child Health. 2006 May;42(5):277-82. doi: 10.1111/j.1440-1754.2006.00854.x.
• Background Ursavas A, Karadag M, Rodoplu E, Yilmaztepe A, Oral HB, Gozu RO. Circulating ICAM-1 and VCAM-1 levels in patients with obstructive sleep apnea syndrome. Respiration. 2007;74(5):525-32. doi: 10.1159/000097770. Epub 2006 Dec 4.
• Background Cofta S, Wysocka E, Dziegielewska-Gesiak S, Michalak S, Piorunek T, Batura-Gabryel H, Torlinski L. Plasma selectins in patients with obstructive sleep apnea. Adv Exp Med Biol. 2013;756:113-9. doi: 10.1007/978-94-007-4549-0_15.
• Background Htoo AK, Greenberg H, Tongia S, Chen G, Henderson T, Wilson D, Liu SF. Activation of nuclear factor kappaB in obstructive sleep apnea: a pathway leading to systemic inflammation. Sleep Breath. 2006 Mar;10(1):43-50. doi: 10.1007/s11325-005-0046-6.
• Background Walsh JA, Duffin KC, Crim J, Clegg DO. Lower frequency of obstructive sleep apnea in spondyloarthritis patients taking TNF-inhibitors. J Clin Sleep Med. 2012 Dec 15;8(6):643-8. doi: 10.5664/jcsm.2254.
• Background Braley TJ, Segal BM, Chervin RD. Sleep-disordered breathing in multiple sclerosis. Neurology. 2012 Aug 28;79(9):929-36. doi: 10.1212/WNL.0b013e318266fa9d. Epub 2012 Aug 15.
• Background Gerdes S, Shakery K, Mrowietz U. Dimethylfumarate inhibits nuclear binding of nuclear factor kappaB but not of nuclear factor of activated T cells and CCAAT/enhancer binding protein beta in activated human T cells. Br J Dermatol. 2007 May;156(5):838-42. doi: 10.1111/j.1365-2133.2007.07779.x. Epub 2007 Mar 23.
• Background Stoof TJ, Flier J, Sampat S, Nieboer C, Tensen CP, Boorsma DM. The antipsoriatic drug dimethylfumarate strongly suppresses chemokine production in human keratinocytes and peripheral blood mononuclear cells. Br J Dermatol. 2001 Jun;144(6):1114-20. doi: 10.1046/j.1365-2133.2001.04220.x.
• Background Wierinckx A, Breve J, Mercier D, Schultzberg M, Drukarch B, Van Dam AM. Detoxication enzyme inducers modify cytokine production in rat mixed glial cells. J Neuroimmunol. 2005 Sep;166(1-2):132-43. doi: 10.1016/j.jneuroim.2005.05.013.
• Background Vandermeeren M, Janssens S, Borgers M, Geysen J. Dimethylfumarate is an inhibitor of cytokine-induced E-selectin, VCAM-1, and ICAM-1 expression in human endothelial cells. Biochem Biophys Res Commun. 1997 May 8;234(1):19-23. doi: 10.1006/bbrc.1997.6570.
• Background Wallbrecht K, Drick N, Hund AC, Schon MP. Downregulation of endothelial adhesion molecules by dimethylfumarate, but not monomethylfumarate, and impairment of dynamic lymphocyte-endothelial cell interactions. Exp Dermatol. 2011 Dec;20(12):980-5. doi: 10.1111/j.1600-0625.2011.01376.x. Epub 2011 Oct 13.
• Background Meissner M, Valesky EM, Kippenberger S, Kaufmann R. Dimethyl fumarate - only an anti-psoriatic medication? J Dtsch Dermatol Ges. 2012 Nov;10(11):793-801. doi: 10.1111/j.1610-0387.2012.07996.x. Epub 2012 Aug 17. English, German.
• Background Scannevin RH, Chollate S, Jung MY, Shackett M, Patel H, Bista P, Zeng W, Ryan S, Yamamoto M, Lukashev M, Rhodes KJ. Fumarates promote cytoprotection of central nervous system cells against oxidative stress via the nuclear factor (erythroid-derived 2)-like 2 pathway. J Pharmacol Exp Ther. 2012 Apr;341(1):274-84. doi: 10.1124/jpet.111.190132. Epub 2012 Jan 20.
• Braley TJ, Huber AK, Segal BM, Kaplish N, Saban R, Washnock-Schmid JM, Chervin RD. A randomized, subject and rater-blinded, placebo-controlled trial of dimethyl fumarate for obstructive sleep apnea. Sleep. 2018 Aug 1;41(8). doi: 10.1093/sleep/zsy109.

Drugs

Indications