The effect of sulthiame on potential biomarkers in moderate to severe obstructive sleep apnoea
Background Obstructive sleep apnoea (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 (HIF)-1α are two potential...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
European Respiratory Society
2024-12-01
|
| Series: | ERJ Open Research |
| Online Access: | http://openres.ersjournals.com/content/10/6/00342-2024.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841537069639270400 |
|---|---|
| author | Erik Hoff Saliha Musovic Ali M. Komai Ding Zou Christian Strassberger Kaj Stenlöf Ludger Grote Jan Hedner |
| author_facet | Erik Hoff Saliha Musovic Ali M. Komai Ding Zou Christian Strassberger Kaj Stenlöf Ludger Grote Jan Hedner |
| author_sort | Erik Hoff |
| collection | DOAJ |
| description | Background
Obstructive sleep apnoea (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 (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.
Methods
This was an exploratory analysis of a randomised, 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 randomised to 4 weeks with placebo, STM 200 mg or STM 400 mg. CA activity (n=43) and HIF-1α concentration (n=53) were determined at baseline, after 4 weeks of treatment and 2 weeks after treatment completion.
Results
In the 400 mg group, both CA activity and HIF-1α concentration were reduced (median difference −26% (95% CI −32– −12%) and −4% (95% CI −8– −2%); both p<0.05 versus placebo). The reductions were sustained 2 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).
Conclusions
STM treatment in OSA induced a reduction of both CA activity and HIF-1α concentration. The effects remained 2 weeks after treatment completion, suggesting prolonged effects of STM in OSA. |
| format | Article |
| id | doaj-art-0d09e7c0a5e041969ef120ec833c51f0 |
| institution | Kabale University |
| issn | 2312-0541 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | European Respiratory Society |
| record_format | Article |
| series | ERJ Open Research |
| spelling | doaj-art-0d09e7c0a5e041969ef120ec833c51f02025-01-14T09:50:21ZengEuropean Respiratory SocietyERJ Open Research2312-05412024-12-0110610.1183/23120541.00342-202400342-2024The effect of sulthiame on potential biomarkers in moderate to severe obstructive sleep apnoeaErik Hoff0Saliha Musovic1Ali M. Komai2Ding Zou3Christian Strassberger4Kaj Stenlöf5Ludger Grote6Jan Hedner7 Centre for Sleep and Vigilance Disorders, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Centre for Sleep and Vigilance Disorders, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Centre for Sleep and Vigilance Disorders, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Centre for Sleep and Vigilance Disorders, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Centre for Sleep and Vigilance Disorders, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Centre for Sleep and Vigilance Disorders, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Centre for Sleep and Vigilance Disorders, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Centre for Sleep and Vigilance Disorders, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Background Obstructive sleep apnoea (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 (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. Methods This was an exploratory analysis of a randomised, 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 randomised to 4 weeks with placebo, STM 200 mg or STM 400 mg. CA activity (n=43) and HIF-1α concentration (n=53) were determined at baseline, after 4 weeks of treatment and 2 weeks after treatment completion. Results In the 400 mg group, both CA activity and HIF-1α concentration were reduced (median difference −26% (95% CI −32– −12%) and −4% (95% CI −8– −2%); both p<0.05 versus placebo). The reductions were sustained 2 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). Conclusions STM treatment in OSA induced a reduction of both CA activity and HIF-1α concentration. The effects remained 2 weeks after treatment completion, suggesting prolonged effects of STM in OSA.http://openres.ersjournals.com/content/10/6/00342-2024.full |
| spellingShingle | Erik Hoff Saliha Musovic Ali M. Komai Ding Zou Christian Strassberger Kaj Stenlöf Ludger Grote Jan Hedner The effect of sulthiame on potential biomarkers in moderate to severe obstructive sleep apnoea ERJ Open Research |
| title | The effect of sulthiame on potential biomarkers in moderate to severe obstructive sleep apnoea |
| title_full | The effect of sulthiame on potential biomarkers in moderate to severe obstructive sleep apnoea |
| title_fullStr | The effect of sulthiame on potential biomarkers in moderate to severe obstructive sleep apnoea |
| title_full_unstemmed | The effect of sulthiame on potential biomarkers in moderate to severe obstructive sleep apnoea |
| title_short | The effect of sulthiame on potential biomarkers in moderate to severe obstructive sleep apnoea |
| title_sort | effect of sulthiame on potential biomarkers in moderate to severe obstructive sleep apnoea |
| url | http://openres.ersjournals.com/content/10/6/00342-2024.full |
| work_keys_str_mv | AT erikhoff theeffectofsulthiameonpotentialbiomarkersinmoderatetosevereobstructivesleepapnoea AT salihamusovic theeffectofsulthiameonpotentialbiomarkersinmoderatetosevereobstructivesleepapnoea AT alimkomai theeffectofsulthiameonpotentialbiomarkersinmoderatetosevereobstructivesleepapnoea AT dingzou theeffectofsulthiameonpotentialbiomarkersinmoderatetosevereobstructivesleepapnoea AT christianstrassberger theeffectofsulthiameonpotentialbiomarkersinmoderatetosevereobstructivesleepapnoea AT kajstenlof theeffectofsulthiameonpotentialbiomarkersinmoderatetosevereobstructivesleepapnoea AT ludgergrote theeffectofsulthiameonpotentialbiomarkersinmoderatetosevereobstructivesleepapnoea AT janhedner theeffectofsulthiameonpotentialbiomarkersinmoderatetosevereobstructivesleepapnoea AT erikhoff effectofsulthiameonpotentialbiomarkersinmoderatetosevereobstructivesleepapnoea AT salihamusovic effectofsulthiameonpotentialbiomarkersinmoderatetosevereobstructivesleepapnoea AT alimkomai effectofsulthiameonpotentialbiomarkersinmoderatetosevereobstructivesleepapnoea AT dingzou effectofsulthiameonpotentialbiomarkersinmoderatetosevereobstructivesleepapnoea AT christianstrassberger effectofsulthiameonpotentialbiomarkersinmoderatetosevereobstructivesleepapnoea AT kajstenlof effectofsulthiameonpotentialbiomarkersinmoderatetosevereobstructivesleepapnoea AT ludgergrote effectofsulthiameonpotentialbiomarkersinmoderatetosevereobstructivesleepapnoea AT janhedner effectofsulthiameonpotentialbiomarkersinmoderatetosevereobstructivesleepapnoea |