The effect of sulthiame on potential biomarkers in moderate to severe obstructive sleep apnea

Abstract

Obstructive sleep apnea (OSA) is a common disease with breathing disturbances during sleep. Sulthiame (STM), a carbonic anhydrase (CA) inhibitor, was recently shown to reduce OSA in a significant proportion of patients. CA activity and hypoxia-inducible factor 1α (HIF-1α) are two potential biomarkers reported in severe OSA and hypoxia. Both have been considered to play roles in the development of OSA comorbidities. This study investigated the effects of STM on these biomarkers in OSA.Exploratory analysis of a randomized, double-blind, placebo controlled trial of STM in OSA. Patients with moderate to severe OSA, body mass index 20–35 kg·m−2, aged 18–75 years and not accepting positive airway pressure treatment were randomized to four weeks with STM 200 mg, STM 400 mg or placebo. CA activity (n=43) and HIF-1α concentration (n=53) were determined at baseline, after four weeks of treatment and two weeks after treatment completion.In the 400 mg group, both CA activity and HIF-1α concentration were reduced (median difference −26% [95% CI −32% to −12%] and −4% [95% CI −8% to −2%], both p<0.05versusplacebo). The reductions were sustained two weeks after treatment completion. In the 200 mg group, both CA activity and HIF-1α were numerically reduced. The STM induced reductions in CA activity and HIF-1α correlated significantly (r=0.443, p=0.023).STM treatment in OSA induced a reduction of both CA activity and HIF-1α concentration. The effects remained two weeks after treatment completion, suggesting prolonged effects of STM in OSA.