A Pilot Study of Antioxidant Therapy in Obstructive Sleep Apnea Patients

Purpose: To determine whether treatment of obstructive sleep apnea (OSA) patients with a potent oral antioxidant (alpha lipoic acid, ALA) improves cardiovascular health. Objectives: The primary objective of the study is to assess the impact of ALA on endothelial function (primary outcome). We will also assess whether ALA improves systemic inflammation and markers of oxidative stress. Background: Increased production of reactive oxygen species (ROS) and consequent oxidative stress results in tissue damage and activation of inflammation, and is a recognized risk factor for the development of cardiovascular disease (CVD). Obstructive sleep apnea (OSA) is a prevalent under-recognized disorder; moderate to severe disease is found in approximately 9% of randomly selected middle-aged men and 4% of women. In addition, patients with OSA are at increased (i.e., 3 fold) risk of incident CVD including myocardial infarction and acute coronary syndromes. OSA is characterized by repetitive episodes of desaturation followed by reoxygenation; this ischemia/reperfusion is a potent stimulus for the production of ROS, and results in high levels of oxidative stress. Indeed, OSA may be considered a prototypical oxidative stress disease. However, few studies have assessed the potential beneficial impact of antioxidant therapy in OSA patients. We hypothesize that antioxidants may mitigate some of the adverse CV consequences associated with OSA. The current proposal builds upon our translational work, and focuses on comprehensively assessing the impact of a routinely used potent antioxidant on CV health. Methods: 80 patients with moderate to severe OSA will be enrolled in a parallel randomized controlled trial (RCT). At baseline, endothelial function will be measured noninvasively using a standard technique (EndoPAT). In addition, we will measure circulating levels of C reactive protein, and markers of oxidative stress (urinary 8-isoprostane and 8-hydroxy-2-deoxy guanosine). Patients will be randomized to either ALA or placebo. Endothelial function and biochemical markers will be remeasured after 12 weeks to determine the impact of ALA. If ALA does result in significant benefits, this would raise the possibility of using ALA as a therapy in OSA patients to prevent CVD, and justify a larger RCT to validate the result. This is of substantial importance given the high prevalence of OSA in the population.