Obstructive Sleep ApneaPhase 4ACTOSNCT04227093
Acetazolamide Add-On Therapy to OSA Surgery
A Phase 4 study testing Acetazolamide in people with Obstructive Sleep Apnea, run by University Hospital, Antwerp at 1 site in Belgium.
Trial summary
Surgical procedures are routinely performed as an alternative to continuous positive airway pressure treatment in patients with obstructive sleep apnea (OSA). However, the response to surgery is often variable. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Obstructive Sleep Apnea
- What is being tested?
- Acetazolamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 1 siteBelgium
- Study dates
- 22 Jan 2020to Aug 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of moderate to severe OSA (i.e. 15≤ AHI <65 events per hour)
- Eligibility for either BRP or UAS surgery
- Fitness for general anesthesia (ASA ≤2)
- Capability of giving informed consent and willingness to undergo surgery
Who cannot join
- Craniofacial anomalies affecting the UA
- Body mass index (BMI) >35 kg/m²
- General contra-indications for surgery
- Central sleep apnea (defined as central AHI ≥5 events per hour)
- Contra-indications related to acetazolamide treatment
- Hypersensitivity to sulfonamides or acetazolamide
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- Renal impairment (eGFR <60 ml/min/1.73m²), electrolyte imbalances (sodium levels <135 mmol/L or potassium levels <3.5 mmol/L) and/or adrenocortical insufficiency
- Clinically significant neurological, metabolic (including diabetes mellitus type 1 or 2), hepatic (alanine transaminase or aspartate transaminase >2 times the upper limit of normal) and/or hematological disease
- Chronic obstructive pulmonary disease
- Closed-angle glaucoma
- Professional driving or handling complex machinery due to the potential risk of exaggerated daytime sleepiness
- Concomitant intake of drugs that influence breathing, sleep, arousal and/or muscle physiology
- Inability of the patient to understand and/or comply to the study procedures
- Active psychiatric disease (psychotic illness, major depression, anxiety attacks, and alcohol or drug abuse) which prevents compliance with the requirements of the research setting
- Pregnancy or willing to become pregnant
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Acetazolamide as add-on Therapy to Obstructive Sleep Apnea Surgery (ACTOS): a Parallel-group, Double-blind, Placebo-controlled, Randomized Trial
Surgical procedures are routinely performed as an alternative to continuous positive airway pressure treatment in patients with obstructive sleep apnea (OSA). However, the response to surgery is often variable. Instability of the respiratory control during sleep (or high loop gain) has been associated with poor surgical results in previous research. Acetazolamide (AZM), a carbonic anhydrase inhibitor, has shown potential in reducing loop gain without affecting other physiological OSA traits. In this protocol the investigators will evaluate the clinical efficacy of AZM add-on therapy to surgical procedures in patients with OSA.
Read the detailed description
Seventy-four patients with diagnosed moderate to severe OSA will be equally (1:1) randomized to AZM (250 mg twice daily) or placebo add-on therapy after surgery. Two surgical procedures will be performed throughout the study: barbed reposition pharyngoplasty (BRP) and upper airway stimulation (UAS) using electrical neurostimulation of the hypoglossal nerve.
Treatment allocation will occur after a satisfactory recovery in patients undergoing BRP and after titration of the device settings in patients treated with UAS. Treatment outcome will be assessed approximately 10 weeks thereafter by in-laboratory polysomnography. Two on-site follow-up visits will be scheduled to assess adherence and adverse events. The maximum treatment duration per participant will amount to 16 weeks.
Besides the aforementioned core clinical part, the study protocol will also include an optional exploratory part prior to surgery, assessing the physiological OSA traits and airflow features by means of polysomnography and drug-induced sleep endoscopy research measurements.
- Conditions
- Obstructive Sleep Apnea
- Being tested
- Acetazolamide, Placebo
- Keywords
- Acetazolamide, Carbonic anhydrase inhibitor, Upper airway stimulation, Surgery
- Medical subject headings
- Sleep Apnea, Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcetazolamideDrug
Also called Diamox, ATC code: S01EC01
Oral acetazolamide tablets of 250 mg taken twice daily.
PlaceboDrug
Matching placebo tablets taken twice daily.
| Study group | Role | What they receive |
|---|---|---|
| Acetazolamide | Active comparator | Acetazolamide will be prescribed in unembellished white capsules of 250 mg. The drug will be administered twice daily in the morning and evening (approximately one hour before bedtime). The total treatment length will amount to 16 weeks. In case of side effects hampering treatment adherence, the daily dosage will be reduced to a single evening dose of 250 mg. Receives: Drug: Acetazolamide |
| Placebo | Placebo comparator | The placebo regimen will be identical. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Apnea-hypopnea index (AHI)
Change in AHI (events/h) from baseline to follow-up. The AHI is an index of sleep apnea severity that encompasses the frequency of apneas (cessations in breathing) and hypopneas (reductions in airflow).
Measured: 10 weeks of add-on therapy
Secondary outcomes (6)
Oxygen desaturation index (ODI)
Change in ODI (events/h) from baseline to follow-up. The ODI represents the average number of desaturation episodes (≥3%) per hour sleep.
Measured: 10 weeks of add-on therapy
Oxygen saturation (SaO2)
Change in mean and minimal SaO2 (%) from baseline to follow-up.
Measured: 10 weeks of add-on therapy
Changes in daytime sleepiness measured with the Epworth Sleepiness Scale (ESS)
The questionnaire asks subjects to rate their probability of falling asleep on a scale from 0 to 3 for eight different situations that most people encounter in their daily lives. The scores for the eight questions are added together to obtain a single number (0-24). An ESS score higher than 10 indicates the presence of excessive daytime sleepiness.
Measured: 16 weeks of add-on therapy
Changes in sleep-related quality of life measured with the Functional Outcome of Sleep Questionnaire (FOSQ-10)
This questionnaire is an abbreviated version of the original 30-item version. The FOSQ-10 consists of 10 items that are distributed among 5 subscales: general productivity (2 items), activity level (3 items), vigilance (3 items), social outcomes (1 item), and intimacy and sexual relationships (1 item). The questionnaire has a 4-point scale. The total score is calculated as the sum of the subscale means and can range from 5 to 20. The minimal important difference ranges from 1.7 to 2.0 points.
Measured: 16 weeks of add-on therapy
Changes in snoring intensity measured with a Visual Analogue Scale (VAS)
If patients have a bed partner, a standard 10-point VAS ranging from 0 (no snoring) to 10 (extreme snoring causing the bed partner to leave the bedroom or sleep separately) will be used to evaluate the subjective status of snoring during sleep. Heavy snoring corresponds to a snoring index of at least 7. A decrease of 3 points after treatment is considered significant. A satisfactory improvements is defined as a reduction to an index that is no longer experiences as bothersome (i.e. <3).
Measured: 16 weeks of add-on therapy
Incidence of adverse events
Safety and tolerability of study treatment.
Measured: 16 weeks of add-on therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2020
- Study start22 Jan 2020
- Primary completion22 Apr 2023
- Study completionAug 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Obstructive Sleep ApneaStudies of the same condition, open and under way.
- More trials run by University Hospital, AntwerpThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, double-blind, placebo-controlled trial
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Antwerp
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, ethisch.comite@uza.be, University Hospital, Antwerp
- Investigators
- Olivier Vanderveken, MD, PhD, Principal investigator, University Hospital, Antwerp
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04227093
- Sponsor's protocol ID
- B300201942507
- Acronym
- ACTOS
- Status last verified
- Jun 2024
- First submitted
- 20 Dec 2019
- Last updated
- 18 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acetazolamide as add-on Therapy to Obstructive Sleep Apnea Surgery (ACTOS): a Parallel-group, Double-blind, Placebo-controlled, Randomized Trial
- ClinicalTrials.gov ID
- NCT04227093
- Acronym / sponsor ID
- ACTOS / B300201942507
- Conditions
- Obstructive Sleep Apnea
- Keywords
- Acetazolamide, Carbonic anhydrase inhibitor, Upper airway stimulation, Surgery
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 26 participants (actual)
- Lead sponsor
- University Hospital, AntwerpUniversity, hospital or other
- Study start
- 22 Jan 2020 (actual)
- Primary completion
- 22 Apr 2023 (actual)
- Study completion
- Aug 2024 (estimated)
- First posted
- 13 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Surgical procedures are routinely performed as an alternative to continuous positive airway pressure treatment in patients with obstructive sleep apnea (OSA). However, the response to surgery is often variable. Instability of the respiratory control during sleep (or high loop gain) has been associated with poor surgical results in previous research. Acetazolamide (AZM), a carbonic anhydrase inhibitor, has shown potential in reducing loop gain without affecting other physiological OSA traits. In this protocol the investigators will evaluate the clinical efficacy of AZM add-on therapy to surgical procedures in patients with OSA.
Detailed description
Seventy-four patients with diagnosed moderate to severe OSA will be equally (1:1) randomized to AZM (250 mg twice daily) or placebo add-on therapy after surgery. Two surgical procedures will be performed throughout the study: barbed reposition pharyngoplasty (BRP) and upper airway stimulation (UAS) using electrical neurostimulation of the hypoglossal nerve.
Treatment allocation will occur after a satisfactory recovery in patients undergoing BRP and after titration of the device settings in patients treated with UAS. Treatment outcome will be assessed approximately 10 weeks thereafter by in-laboratory polysomnography. Two on-site follow-up visits will be scheduled to assess adherence and adverse events. The maximum treatment duration per participant will amount to 16 weeks.
Besides the aforementioned core clinical part, the study protocol will also include an optional exploratory part prior to surgery, assessing the physiological OSA traits and airflow features by means of polysomnography and drug-induced sleep endoscopy research measurements.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
- Model description
- Randomized, double-blind, placebo-controlled trial
| Arm | Type | Receives |
|---|---|---|
| Acetazolamide | Active comparator | Drug: AcetazolamideAcetazolamide will be prescribed in unembellished white capsules of 250 mg. The drug will be administered twice daily in the morning and evening (approximately one hour before bedtime). The total treatment length will amount to 16 weeks. In case of side effects hampering treatment adherence, the daily dosage will be reduced to a single evening dose of 250 mg. |
| Placebo | Placebo comparator | Drug: PlaceboThe placebo regimen will be identical. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Diagnosis of moderate to severe OSA (i.e. 15≤ AHI <65 events per hour)
- Eligibility for either BRP or UAS surgery
- Fitness for general anesthesia (ASA ≤2)
- Capability of giving informed consent and willingness to undergo surgery
Key exclusion criteria (15 listed)
- Craniofacial anomalies affecting the UA
- Body mass index (BMI) >35 kg/m²
- General contra-indications for surgery
- Central sleep apnea (defined as central AHI ≥5 events per hour)
- Contra-indications related to acetazolamide treatment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AcetazolamideAlso: Diamox, ATC code: S01EC01Oral acetazolamide tablets of 250 mg taken twice daily. | Drug | Acetazolamide |
| PlaceboMatching placebo tablets taken twice daily. | Drug | Placebo |
Primary outcome
Apnea-hypopnea index (AHI)
Time frame: 10 weeks of add-on therapy
Change in AHI (events/h) from baseline to follow-up. The AHI is an index of sleep apnea severity that encompasses the frequency of apneas (cessations in breathing) and hypopneas (reductions in airflow).
6 secondary outcomes
Oxygen desaturation index (ODI)
Time frame: 10 weeks of add-on therapy
Oxygen saturation (SaO2)
Time frame: 10 weeks of add-on therapy
Changes in daytime sleepiness measured with the Epworth Sleepiness Scale (ESS)
Time frame: 16 weeks of add-on therapy
Changes in sleep-related quality of life measured with the Functional Outcome of Sleep Questionnaire (FOSQ-10)
Time frame: 16 weeks of add-on therapy
Changes in snoring intensity measured with a Visual Analogue Scale (VAS)
Time frame: 16 weeks of add-on therapy
Incidence of adverse events
Time frame: 16 weeks of add-on therapy
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Olivier Vanderveken, MD, PhD principal investigator
University Hospital, Antwerp
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Acetazolamide in people with Obstructive Sleep Apnea, run by University Hospital, Antwerp at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Apnea-hypopnea index (AHI) (time frame: 10 weeks of add-on therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2024.