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

Erik Hoff1,2, Saliha Musovic1, Ali M Komai1

  • 1Centre for Sleep and Vigilance Disorders, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

ERJ Open Research
|December 3, 2024
PubMed
Abstract

Insights

Sulthiame (STM) treatment for obstructive sleep apnoea (OSA) significantly reduced carbonic anhydrase (CA) activity and hypoxia-inducible factor (HIF)-1α. These positive effects on OSA biomarkers persisted for two weeks post-treatment.

Area of Science:

  • Sleep Medicine
  • Pharmacology
  • Biochemistry

Background:

  • Obstructive sleep apnoea (OSA) is a prevalent condition characterized by sleep-related breathing disturbances.
  • Carbonic anhydrase (CA) activity and hypoxia-inducible factor (HIF)-1α are implicated as biomarkers in severe OSA and hypoxia, potentially contributing to comorbidities.
  • Sulthiame (STM), a carbonic anhydrase inhibitor, has shown promise in improving OSA in a subset of patients.

Purpose of the Study:

  • To investigate the impact of Sulthiame (STM) on carbonic anhydrase (CA) activity and hypoxia-inducible factor (HIF)-1α concentration in patients with obstructive sleep apnoea (OSA).
  • To explore the potential of these biomarkers as indicators of STM's therapeutic effects in OSA.

Main Methods:

  • An exploratory analysis of a randomized, double-blind, placebo-controlled trial involving patients with moderate to severe OSA.
  • Participants received placebo, 200 mg STM, or 400 mg STM for 4 weeks.
  • CA activity and HIF-1α levels were measured at baseline, after 4 weeks of treatment, and 2 weeks post-treatment.

Main Results:

  • The 400 mg STM group showed significant reductions in both CA activity (median difference -26%) and HIF-1α concentration (median difference -4%) compared to placebo (p<0.05).
  • These reductions were sustained two weeks after treatment cessation.
  • Numerical reductions in CA activity and HIF-1α were observed in the 200 mg STM group, with a significant correlation between STM-induced reductions in CA activity and HIF-1α (r=0.443, p=0.023).

Conclusions:

  • Sulthiame (STM) treatment effectively reduces carbonic anhydrase (CA) activity and hypoxia-inducible factor (HIF)-1α concentration in patients with obstructive sleep apnoea (OSA).
  • The observed effects on these biomarkers persisted for two weeks after treatment completion, suggesting prolonged therapeutic action of STM in OSA.

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