Acetazolamide as a Means to Mitigate Falling Ventilatory Drive and Drive-dependent OSA

NCT06091085 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 2023P002472
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

Obstructive sleep apnea (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. For years, a "classic" model of OSA has been used to describe the disorder, which fails to capture it's complexity. Recently, a model for OSA called drive-dependent OSA was discovered be more prevalent in the OSA population. This drive-dependent OSA is due to ventilation instability that occurs during respiratory events however these individuals have spontaneous increases in drive during respiratory events that stabilize their airway (i.e., via improving upper airway muscle activity) and reduce the risk of respiratory events in people with OSA. Therefore, by stabilizing the ventilatory drive, OSA should be treatable. Acetazolamide is a pharmacological ventilatory stimulant and has been previously shown to reduce OSA severity. As such in this study, the goal is to demonstrate acetazolamide improves OSA severity in 'drive-dependent' OSA people by improving drive-related pharyngeal obstructions compared to the 'classic' OSA people.

Conditions

OSA

Outcome Measures

Primary Outcomes (1)

• Percentage reduction of apnea-hypopnea Index (AHI) with active versus placebo therapy in drive-dependent vs classic OSA groups

  The primary efficacy outcome measure is the apnea hypopnea index (3% desaturation or arousal), presented as a percent reduction from baseline. Differences in this measure with active versus placebo therapy will be assessed. The primary comparison will be the difference in this measure in drive-dependent versus classic OSA subgroups.

  1 night

Secondary Outcomes (3)

• Hypoxic burden, %.min/hr

  1 night

• Arousal index, events/hr

  1 night

• N1 sleep, %total sleep time

  1 night

Study Arms (2)

Acetazolamide

EXPERIMENTAL

Acetazolamide administered for 3 nights, half-dose (1 pill) on the first night followed by full dose (2x250mg pills) for 2 nights

Drug: Acetazolamide

Placebo

PLACEBO COMPARATOR

Placebo sugar pills administered for 3 nights, half-dose (1 pill) on the first night followed by full dose (2 pills) for 2 nights

Drug: Placebo

Interventions

Acetazolamide DRUG

Administered for 3 nights, half-dose (1 pill) on the first night followed by full dose (2x250mg pills) for 2 nights

Acetazolamide

Placebo DRUG

Placebo sugar pills administered for 3 nights, half-dose (1 pill) on the first night followed by full dose (2 pills) for 2 nights

Placebo

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ages 21-80 years
• Suspected OSA (snoring, sleepiness, witnessed apneas, other clinical symptoms) or diagnosed OSA (severity not required)
• Untreated; No use of OSA treatments within 2 weeks of the baseline study. No plans to start OSA treatments for the duration of the study protocol

You may not qualify if:

• Any unstable medical condition
• Current use of the study medication.
• Use of ventilatory stimulant or depressant medications that may complicated interpretation of results (including opioids, barbiturates, doxapram, almitrine, theophylline, 4-hydroxybutanoic acid).
• Contraindications for acetazolamide, including:
• Allergies to sulfonamides - e.g. acetazolamide, hydrochlorothiazide, furosemide, sulfasalazine, celecoxib, sumatriptan, and zonisamide.
• closed-angle glaucoma
• adrenal insufficiency
• known electrolyte or acid/base imbalance (hyponatremia, hypokalemia, hyperchloremia, metabolic acidosis, acidemia)
• clinically-significant kidney disorders (eGFR\<60 ml/min/1.73m2)
• clinically-significant liver disorders
• Use of more than 500 mg/day of Aspirin, due to the potential for an interaction of acetazolamide and very high doses of Aspirin (acetylsalicylic acid, a salicylate drug)
• Adrenocortical insufficiency
• Low sodium or potassium
• hyperchloremic acidosis
• Conditions likely to affect obstructive sleep apnea physiology: neuromuscular disease or other major neurological disorder, heart failure, or any other unstable major medical condition.

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02141, United States

RECRUITING

MeSH Terms

Interventions

Acetazolamide

Intervention Hierarchy (Ancestors)

Thiadiazoles; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Dillon Gilbertson

  Brigham and Women's Hospital and Harvard Medical School

  STUDY DIRECTOR

• Scott Sands, PhD

  Brigham and Women's Hospital and Harvard Medical School

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Scott Sands, PhD

CONTACT

8579280341; sasands@bwh.harvard.edu

Atqiya Aishah, PhD

CONTACT

aaishah@bwh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 4-week open-label acetazolamide extension and optional
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: October 16, 2023
• First Posted: October 19, 2023
• Study Start: January 31, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 4, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Deidentified data will be shared freely with collaborating scientists at any time and more broadly to other scientists 12 months following all planned publications using the data.
• Access Criteria: Requests should be made in writing to the lead investigator.

Locations

US (1)