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Acetazolamide on REM OSA (RemmOSA)

Primary Purpose

Obstructive Sleep Apnea

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Placebo oral capsule
Acetazolamide
Sponsored by
Brigham and Women's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Obstructive Sleep Apnea

Eligibility Criteria

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

Inclusion Criteria:

  • Diagnosed REM OSA (per baseline screening: REM AHI/nREM AHI≥2) [31-33]
  • REM duration>10 minutes
  • Not using CPAP (>1 week).

Exclusion Criteria:

  • Any uncontrolled medical condition
  • Current use of the medications under investigation
  • Use of medications expected to stimulate or depress respiration (including opioids, barbiturates, doxapram, almitrine, theophylline, 4-hydroxybutanoic acid).
  • Conditions likely to affect obstructive sleep apnea physiology: neuromuscular disease or other major neurological disorder, heart failure (also below), or any other unstable major medical condition.
  • Respiratory disorders other than sleep disordered breathing:

chronic hypoventilation/hypoxemia (awake SaO2 < 92% by oximetry) due to chronic obstructive pulmonary disease or other respiratory conditions.

  • Other sleep disorders: periodic limb movements (periodic limb movement arousal index > 10/hr), narcolepsy, or parasomnias.

  • Contraindications for acetazolamide, including:

    • Hyperchloremic acidosis
    • Hypokalemia
    • Hyponatremia
    • Adrenal insufficiency
    • Impaired kidney function
    • Hypersensitivity to acetazolamide or other sulfonamides.
    • Marked liver disease or impairment of liver function, including cirrhosis.
  • Contraindications to the use of lidocaine 4%/oxymetazoline HCT.
  • Claustrophobia
  • Pregnancy or nursing

Sites / Locations

  • Brigham and Women's HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo

Acetazolamide

Arm Description

Placebo capsule before bedtime for 3 nights before the studies (inclusive)

Acetazolamide 250 mg before bedtime 3 nights before the study, Acetazolamide 500 mg before bedtime for 2 nights before the study (inclusive)

Outcomes

Primary Outcome Measures

Apnea hypopnea index
Number of events/hour of sleep
Hypoxic burden
The total area under the respiratory event-related desaturation curve, measured as in %min/hr
Ventilatory drive in REM and NREM
Ventilatory drive will be calculated using diaphragm EMG (as percent of eupneic ventilatory drive)
Genioglossus activity in REM and NREM
Genioglossus activity will be calculated using EMG wires under the tongue (as percent of eupneic activity or maximal activity)

Secondary Outcome Measures

Full Information

First Posted
October 18, 2022
Last Updated
February 6, 2023
Sponsor
Brigham and Women's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05589792
Brief Title
Acetazolamide on REM OSA
Acronym
RemmOSA
Official Title
The Effect of Acetazolamide on the Severity of REM Obstructive Sleep Apnea
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 30, 2023 (Actual)
Primary Completion Date
September 1, 2023 (Anticipated)
Study Completion Date
December 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brigham and Women's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
OSA is a highly prevalent disorder that has major consequences for cardiovascular health, neurocognitive function, risk of traffic accidents, daytime sleepiness and quality of life. In particular, REM sleep is accompanied by more frequent and longer obstructive events, that yield more profound hypoxemia than during non-REM (nREM). Exaggerated OSA severity in REM is the consequence of ventilatory drive dips, particularly during phasic eye movements. Unfortunately, the leading treatment for REM and nREM OSA, CPAP-which acts to pneumatically splint the pharynx open-is intolerable for many patients. Treatment outcomes for REM OSA are burdened by further incomplete CPAP adherence later in the night, which commonly leaves REM periods undertreated. In this protocol, the investigators will test the effect of Acetazolamide on REM OSA and on ventilatory parameters such as genioglossus muscle activity and ventilatory drive.
Detailed Description
After a baseline home sleep test that will assess the presence of OSA and REM OSA, two overnight, in-lab sleep studies will be performed: a drug night and a placebo night. The patient will breath spontaneously (without CPAP) for both nights. On the study nights, subjects will present to the laboratory in the evening and be instrumented with a full polysomnigraphy for monitoring sleep, physiological variables (endotypes), and respiratory events. Participants will also be instrumented with EMG wires and introesophageal catheter for the recording of genioglossus muscle activity and respiratory drive, respectively. A history and physical examination will be performed on each night prior to beginning the study, as will a urine pregnancy test in premenopausal women. Acetazolamide 500 mg will be taken for 2 days (including the day of the study), after a day in which it will be administered at half dose, before bedtime. Subjects will sleep at least 50% of the night in the supine position. At least four hours of sleep with high quality signal acquisition will be required for a study to be judged adequate. Subjective sleep quality will be assessed in the morning. After the first overnight study is completed, there will be a four day washout period prior to crossing over to the other treatment

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obstructive Sleep Apnea

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo capsule before bedtime for 3 nights before the studies (inclusive)
Arm Title
Acetazolamide
Arm Type
Active Comparator
Arm Description
Acetazolamide 250 mg before bedtime 3 nights before the study, Acetazolamide 500 mg before bedtime for 2 nights before the study (inclusive)
Intervention Type
Drug
Intervention Name(s)
Placebo oral capsule
Intervention Description
Placebo before sleep for 3 nights before the study (inclusive)
Intervention Type
Drug
Intervention Name(s)
Acetazolamide
Intervention Description
Acetazolamide 250 mg 3 nights before the study at bedtime, Acetazolamide 500 mg for 2 nights before the study (inclusive) at bedtime.
Primary Outcome Measure Information:
Title
Apnea hypopnea index
Description
Number of events/hour of sleep
Time Frame
1 night
Title
Hypoxic burden
Description
The total area under the respiratory event-related desaturation curve, measured as in %min/hr
Time Frame
1 night
Title
Ventilatory drive in REM and NREM
Description
Ventilatory drive will be calculated using diaphragm EMG (as percent of eupneic ventilatory drive)
Time Frame
1 night
Title
Genioglossus activity in REM and NREM
Description
Genioglossus activity will be calculated using EMG wires under the tongue (as percent of eupneic activity or maximal activity)
Time Frame
1 night

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosed REM OSA (per baseline screening: REM AHI/nREM AHI≥2) [31-33] REM duration>10 minutes Not using CPAP (>1 week). Exclusion Criteria: Any uncontrolled medical condition Current use of the medications under investigation Use of medications expected to stimulate or depress respiration (including opioids, barbiturates, doxapram, almitrine, theophylline, 4-hydroxybutanoic acid). Conditions likely to affect obstructive sleep apnea physiology: neuromuscular disease or other major neurological disorder, heart failure (also below), or any other unstable major medical condition. Respiratory disorders other than sleep disordered breathing: chronic hypoventilation/hypoxemia (awake SaO2 < 92% by oximetry) due to chronic obstructive pulmonary disease or other respiratory conditions. Other sleep disorders: periodic limb movements (periodic limb movement arousal index > 10/hr), narcolepsy, or parasomnias. Contraindications for acetazolamide, including: Hyperchloremic acidosis Hypokalemia Hyponatremia Adrenal insufficiency Impaired kidney function Hypersensitivity to acetazolamide or other sulfonamides. Marked liver disease or impairment of liver function, including cirrhosis. Contraindications to the use of lidocaine 4%/oxymetazoline HCT. Claustrophobia Pregnancy or nursing
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ludovico Messineo, MD, PhD
Phone
8572726188
Email
lmessineo@bwh.harvard.edu
Facility Information:
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nicole Calianese, BS
Phone
617-732-8976
Email
ncalianese@partners.org

12. IPD Sharing Statement

Plan to Share IPD
No

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Acetazolamide on REM OSA

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