A University of Gothenburg study has paved the way for the first drug treatment for sleep apnoea. Compared with before receiving the treatment, breathing pauses per hour decreased, on average, by more than 20 for patients who were given the drug.
The treatment tested by the researchers is carbonic anhydrase (CA) inhibition, CA being an enzyme that maintains a balance between carbonic acid and carbon dioxide in the body. Several drugs with CA inhibitory properties are already available on the market, and used for treatment of glaucoma, epilepsy and other disorders.
Previous research has not systematically tested whether CA inhibitors also might be used to treat obstructive sleep apnoea. The current study was a randomised double-blind clinical trial, completed by 59 patients with moderate or severe sleep apnoea.
Patients were randomly assigned to two groups receiving either 400mg or 200mg of the CA inhibitor, and a third group (the control group) that received placebo. The study lasted for four weeks.
Fewer breathing pauses
The results showed that, overall, the treatment reduced the number of breathing pauses and promoted oxygenation during the night. A few patients experienced side effects, such as headache and breathlessness, which were more common in those receiving the highest dose.
The study results and established safety data of the drug sulthiame provide support for continued research on CA inhibition as a new potential treatment for obstructive sleep apnoea.
“Among the patients who received the higher dosage of the drug, the number of breathing pauses decreased by approximately 20 per hour. For just more than a third of patients in the study, only half of their breathing pauses were left, and in one in five the number fell by at least 60%,” said Jan Hedner, professor of Pulmonary Medicine at Gothenburg University.
That several approved drugs in the CA inhibitor category are available on the market makes fast-tracking development of an approved drug for sleep apnoea practicable. The drug used in this clinical trial was sulthiame, which is sometimes used to treat epilepsy in children.
Treatment options needed
Today, treatment for a patient with sleep apnoea is either an oral appliance therapy or a CPAP (Continuous Positive Airway Pressure) mask. Both help to maintain airway patency during sleep.
“These therapy options take time to get used to and, since they frequently are perceived as intrusive or bulky, insufficient user time is therefore common. If we develop an effective drug, it will make life easier for many patients and, in the long run, potentially also save more lives,” said Ludger Grote, senior lecturer at Sahlgrenska Academy, University of Gothenburg.
The results were published in the American Journal of Respiratory and Critical Care Medicine.
Study details
A Randomised Controlled Trial Exploring Safety and Tolerability of Sulthiame in Sleep Apnoea
Jan Hedner, Kaj Stenlöf, Ding Zou, Erik Hoff, Corinna Hansen, Katrin Kuhn, Peter Lennartz, Ludger Grote.
Published in the American Journal of Respiratory and Critical Care Medicine on 24 February 2022.
Abstract
Rational
Current therapies in obstructive sleep apnoea (OSA) are limited by insufficient efficacy, compliance or tolerability. An effective pharmacological treatment in OSA is warranted. Carbonic anhydrase (CA) inhibition has been shown to ameliorate OSA.
Objective
To explore safety and tolerability of the CA inhibitor sulthiame (STM) in OSA.
Methods
A four week double-blind, randomised, placebo-controlled dose guiding trial in patients with moderate/severe OSA not tolerating positive airway pressure treatment. Measurements and results: Intermittent paresthesia was reported by 79, 67 and 18% of patients receiving 400 mg STM (N=34), 200 mg STM (N=12) or placebo (N=22), respectively. Dyspnea was reported only after 400 mg STM (18%). Six patients in the higher dose group withdrew due to an adverse event. There were no serious adverse events. STM reduced the apnea-hypopnea index (AHI) from 55.3 to 33.1 events/h ( 41.0%) in the 400 mg group and from 61.2 to 40.7 events/h ( 32.1%) after 200 mg (p<0.001, respectively). Corresponding placebo values were 53.9 and 50.9 events/h ( 5.4 %).
The AHI reduction threshold of ≥50% was reached in 40% after 400 mg, 25% after 200 mg and 5% following placebo. Mean overnight oxygen saturation improved by 1.1% after 400 mg and 200 mg (p<0.001 and p=0.034, respectively). Patient related outcomes were unchanged. Conclusions: STM showed a satisfactory safety profile in moderate/severe OSA. STM reduced OSA by more than 20 events/h, one of the strongest reductions reported in a drug trial in OSA. Larger scale clinical studies of STM in OSA are justified.
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