Obstructive Sleep Apnea (OSA) and Sex-Specific Responses to N-acetylcysteine (NAC)

Basis of Sex-specific Therapeutic Responses to Obstructive Sleep Apnea (OSA): a Trial of N-acetylcysteine (NAC) in Obstructive Sleep Apnea (OSA)

This is a randomized controlled trial (RCT) of 4 weeks of study supplement N-acetylcysteine (NAC) versus placebo in persons with significant obstructive sleep apnea (OSA) who are receiving positive airway pressure therapy (PAP), the standard of care therapy. The purpose of the study is to determine if NAC is associated with sex-specific changes in overnight oxidative stress, inflammation, as well as endothelial dysfunction in persons with OSA.

Inclusion Criteria:

• Apnea-hypopnea index ≥15 events/hr on portable sleep monitoring
• HbA1c <6.5%

Exclusion Criteria:

• Body mass index (BMI) ≥40 kg/m2;
• Diagnosis of diabetes mellitus, defined as the use of any diabetes medication (including glucagon like peptide [GLP]-1 agonists) currently or in the previous three months or HbA1c ≥6.5%;
• Shift work (i.e., working hours that routinely cause sleep initiation after 1:00 a.m.);
• Another major sleep disorder (i.e., circadian rhythm disorder, any history of narcolepsy, concurrently diagnosed or medication-treated restless legs syndrome, concurrently diagnosed or medication-treated chronic insomnia with the exception of antidepressant therapy);
• Regular use (more than twice/week) of an opioid/narcotic, benzodiazepine, or prescription sleep medication other than antidepressants currently or within the last month;
• The use of N-acetylcysteine in any form (oral, intravenous, inhaled) in the last seven days
• The use of other over-the-counter antioxidant therapies including vitamin C or vitamin E in the preceding 10 days
• History of reduced ejection fraction heart failure, or chronic cardiac arrhythmia requiring medication or treatment;
• Unstable or uncontrolled medical or psychiatric comorbidity requiring hospitalization or change in medication during the previous three months;
• Use of biologics or immune modulators in the last year;
• Use of systemic steroids during the previous three months;
• Current tobacco smoking;
• Inability to sign informed consent;
• Currently use of positive airway pressure therapy or another OSA treatment (e.g., hypoglossal nerve stimulator, oral device);
• Recent history of alcoholism or drug abuse (within the last three months)
• Neurological condition that requires ongoing pharmacological therapy (e.g., Parkinson's disease, Alzheimer's dementia, multiple sclerosis, other degenerative neurological disease).
• Pregnancy