search
Back to results

Acetazolamide Add-On Therapy to OSA Surgery (ACTOS)

Primary Purpose

Obstructive Sleep Apnea

Status
Unknown status
Phase
Phase 4
Locations
Belgium
Study Type
Interventional
Intervention
Acetazolamide
Placebo
Sponsored by
University Hospital, Antwerp
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Obstructive Sleep Apnea focused on measuring Acetazolamide, Carbonic anhydrase inhibitor, Upper airway stimulation, Surgery

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
    • 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

Sites / Locations

  • Antwerp University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Acetazolamide

Placebo

Arm Description

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.

The placebo regimen will be identical.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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.
Oxygen saturation (SaO2)
Change in mean and minimal SaO2 (%) from baseline to follow-up.
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.
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.
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).
Incidence of adverse events
Safety and tolerability of study treatment.

Full Information

First Posted
December 20, 2019
Last Updated
January 23, 2020
Sponsor
University Hospital, Antwerp
search

1. Study Identification

Unique Protocol Identification Number
NCT04227093
Brief Title
Acetazolamide Add-On Therapy to OSA Surgery
Acronym
ACTOS
Official Title
Acetazolamide as add-on Therapy to Obstructive Sleep Apnea Surgery (ACTOS): a Parallel-group, Double-blind, Placebo-controlled, Randomized Trial
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Unknown status
Study Start Date
January 22, 2020 (Actual)
Primary Completion Date
December 2022 (Anticipated)
Study Completion Date
December 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital, Antwerp

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obstructive Sleep Apnea
Keywords
Acetazolamide, Carbonic anhydrase inhibitor, Upper airway stimulation, Surgery

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Randomized, double-blind, placebo-controlled trial
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
74 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Acetazolamide
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
The placebo regimen will be identical.
Intervention Type
Drug
Intervention Name(s)
Acetazolamide
Other Intervention Name(s)
Diamox, ATC code: S01EC01
Intervention Description
Oral acetazolamide tablets of 250 mg taken twice daily.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo tablets taken twice daily.
Primary Outcome Measure Information:
Title
Apnea-hypopnea index (AHI)
Description
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).
Time Frame
10 weeks of add-on therapy
Secondary Outcome Measure Information:
Title
Oxygen desaturation index (ODI)
Description
Change in ODI (events/h) from baseline to follow-up. The ODI represents the average number of desaturation episodes (≥3%) per hour sleep.
Time Frame
10 weeks of add-on therapy
Title
Oxygen saturation (SaO2)
Description
Change in mean and minimal SaO2 (%) from baseline to follow-up.
Time Frame
10 weeks of add-on therapy
Title
Changes in daytime sleepiness measured with the Epworth Sleepiness Scale (ESS)
Description
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.
Time Frame
16 weeks of add-on therapy
Title
Changes in sleep-related quality of life measured with the Functional Outcome of Sleep Questionnaire (FOSQ-10)
Description
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.
Time Frame
16 weeks of add-on therapy
Title
Changes in snoring intensity measured with a Visual Analogue Scale (VAS)
Description
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).
Time Frame
16 weeks of add-on therapy
Title
Incidence of adverse events
Description
Safety and tolerability of study treatment.
Time Frame
16 weeks of add-on therapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Eli Van de Perck, MD
Phone
38213436
Ext
+32
Email
eli.vandeperck@uza.be
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Olivier Vanderveken, MD, PhD
Organizational Affiliation
University Hospital, Antwerp
Official's Role
Principal Investigator
Facility Information:
Facility Name
Antwerp University Hospital
City
Edegem
State/Province
Antwerp
ZIP/Postal Code
2650
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eli Van de Perck, MD
First Name & Middle Initial & Last Name & Degree
Olivier Vanderveken, MD, PhD

12. IPD Sharing Statement

Learn more about this trial

Acetazolamide Add-On Therapy to OSA Surgery

We'll reach out to this number within 24 hrs