Obstructive Sleep Apnea (OSA) and Sex-Specific Responses to N-acetylcysteine (NAC)

Basis of Sex-specific Therapeutic Responses to Obstructive Sleep Apnea (OSA): a Trial of N-acetylcysteine (NAC) in Obstructive Sleep Apnea (OSA)

This is a randomized controlled trial (RCT) of 4 weeks of study supplement N-acetylcysteine (NAC) versus placebo in persons with significant obstructive sleep apnea (OSA) who are receiving positive airway pressure therapy (PAP), the standard of care therapy. The purpose of the study is to determine if NAC is associated with sex-specific changes in overnight oxidative stress, inflammation, as well as endothelial dysfunction in persons with OSA.

Study Overview

• Status: Active, not recruiting
• Conditions: Obstructive Sleep Apnea
• Intervention / Treatment: Dietary supplement: N-acetylcysteine (NAC); Procedure: Positive Airway Pressure (PAP) Therapy; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Apnea-hypopnea index ≥15 events/hr on portable sleep monitoring
• HbA1c <6.5%

Exclusion Criteria:

• Body mass index (BMI) ≥40 kg/m2;
• Diagnosis of diabetes mellitus, defined as the use of any diabetes medication (including glucagon like peptide [GLP]-1 agonists) currently or in the previous three months or HbA1c ≥6.5%;
• Shift work (i.e., working hours that routinely cause sleep initiation after 1:00 a.m.);
• Another major sleep disorder (i.e., circadian rhythm disorder, any history of narcolepsy, concurrently diagnosed or medication-treated restless legs syndrome, concurrently diagnosed or medication-treated chronic insomnia with the exception of antidepressant therapy);
• Regular use (more than twice/week) of an opioid/narcotic, benzodiazepine, or prescription sleep medication other than antidepressants currently or within the last month;
• The use of N-acetylcysteine in any form (oral, intravenous, inhaled) in the last seven days
• The use of other over-the-counter antioxidant therapies including vitamin C or vitamin E in the preceding 10 days
• History of reduced ejection fraction heart failure, or chronic cardiac arrhythmia requiring medication or treatment;
• Unstable or uncontrolled medical or psychiatric comorbidity requiring hospitalization or change in medication during the previous three months;
• Use of biologics or immune modulators in the last year;
• Use of systemic steroids during the previous three months;
• Current tobacco smoking;
• Inability to sign informed consent;
• Currently use of positive airway pressure therapy or another OSA treatment (e.g., hypoglossal nerve stimulator, oral device);
• Recent history of alcoholism or drug abuse (within the last three months)
• Neurological condition that requires ongoing pharmacological therapy (e.g., Parkinson's disease, Alzheimer's dementia, multiple sclerosis, other degenerative neurological disease).
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NAC; Following run-in PAP therapy per standard clinical care for 12 weeks, participants randomized to the NAC arm will also receive the supplement N-acetylcysteine (NAC) for four weeks while remaining on PAP therapy.	Dietary supplement: N-acetylcysteine (NAC); Participants will take two NAC 600mg capsules daily for four weeks.; Procedure: Positive Airway Pressure (PAP) Therapy; All participants will receive PAP therapy per standard of care for OSA.
Experimental: Placebo; Following run-in PAP therapy per standard clinical care for 12 weeks, participants randomized to the placebo arm will also receive placebo for four weeks while remaining on PAP therapy.	Procedure: Positive Airway Pressure (PAP) Therapy; All participants will receive PAP therapy per standard of care for OSA.; Dietary supplement: Placebo; Participants will take two placebo 600mg capsules daily for four weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Overnight Levels of Glutathione (GSH)	GSH measured using participant blood samples.	Baseline, Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
Mean Change in Pre- to Post-Sleep GSH Levels	GSH measured using participant blood samples.	Baseline
Mean Change in Pre- to Post-Sleep GSH Levels	GSH measured using participant blood samples.	Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ratio of GSH to oxidized GSH (GSSG) (GSH:GSSG)	GSH:GSSG measured using participant blood samples.	Baseline
Ratio of GSH to oxidized GSH (GSSG) (GSH:GSSG)	GSH:GSSG measured using participant blood samples.	Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
8-Isoprostane Level	8-isoprostane levels measured using participant blood samples.	Baseline
8-Isoprostane Level	8-isoprostane levels measured using participant blood samples.	Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
Plasma Nitrate Level	Plasma nitrate levels measured using participant blood samples.	Baseline
Plasma Nitrate Level	Plasma nitrate levels measured using participant blood samples.	Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
Plasma Nitrite Level	Plasma nitrite levels measured using participant blood samples.	Baseline
Plasma Nitrite Level	Plasma nitrite levels measured using participant blood samples.	Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
Organic Nitrite Level	Organic nitrite levels measured using participant blood samples.	Baseline
Organic Nitrite Level	Organic nitrite levels measured using participant blood samples.	Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
Interleukin 6 (IL-6) Level	IL-6 levels measured using participant blood samples.	Baseline
Interleukin 6 (IL-6) Level	IL-6 levels measured using participant blood samples.	Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
Tumor Necrosis Factor-alpha (TNFα) Receptor-1 (TNFα-R1) Level	TNFα-R1 levels measured using participant blood samples.	Baseline
Tumor Necrosis Factor-alpha (TNFα) Receptor-1 (TNFα-R1) Level	TNFα-R1 levels measured using participant blood samples.	Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
Tumor Necrosis Factor-alpha (TNFα) Receptor-2 (TNFα-R2) Level	TNFα-R2 levels measured using participant blood samples.	Baseline
Tumor Necrosis Factor-alpha (TNFα) Receptor-2 (TNFα-R2) Level	TNFα-R2 levels measured using participant blood samples.	Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
Reactive Hyperemia Index (RHI) Score	RHI is a measure of endothelial-dependent vasodilation and is assessed using a noninvasive vascular tone measure (EndoPAT®). RHI reflects endothelial health, with lower scores signifying more dysfunction. RHI less than 1.67 is considered a sign of endothelial dysfunction and RHI equal to or greater than 1.67 is considered normal function.	Baseline
Reactive Hyperemia Index (RHI) Score	RHI is a measure of endothelial-dependent vasodilation and is assessed using a noninvasive vascular tone measure (EndoPAT®). RHI reflects endothelial health, with lower scores signifying more dysfunction. RHI less than 1.67 is considered a sign of endothelial dysfunction and RHI equal to or greater than 1.67 is considered normal function.	Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
Epworth Sleepiness Scale (ESS) Score	ESS is an 8-item questionnaire assessing usual likelihood of falling asleep during each of eight common activities. Each item is rated on a Likert scale from 0-3. The total score is the sum of responses and ranges from 0-24; higher scores indicate greater subjective daytime sleepiness.	Baseline
Epworth Sleepiness Scale (ESS) Score	ESS is an 8-item questionnaire assessing usual likelihood of falling asleep during each of eight common activities. Each item is rated on a Likert scale from 0-3. The total score is the sum of responses and ranges from 0-24; higher scores indicate greater subjective daytime sleepiness.	Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
Insomnia Severity Index (ISI) Score	ISI is a 7-item questionnaire assessing the nature, severity, and impact of insomnia. Each item is rated on a 5-point Likert scale from 0-4. The total score is the sum of responses and ranges from 0-28. Scores are interpreted as follows: absence of insomnia (0-7); sub-threshold insomnia (8-14); moderate insomnia (15-21); or severe insomnia (21-28).	Baseline
Insomnia Severity Index (ISI) Score	ISI is a 7-item questionnaire assessing the nature, severity, and impact of insomnia. Each item is rated on a 5-point Likert scale from 0-4. The total score is the sum of responses and ranges from 0-28. Scores are interpreted as follows: absence of insomnia (0-7); sub-threshold insomnia (8-14); moderate insomnia (15-21); or severe insomnia (22-28).	Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
Fatigue Severity Scale (FSS) Score	FSS is a 9-item measure of fatigue severity from a variety of medical and neurological disorders. Each item is rated on a Likert scale from 1-7. The total score is the sum of responses and ranges from 9-63, with higher scores indicating greater fatigue.	Baseline
Fatigue Severity Scale (FSS) Score	FSS is a 9-item measure of fatigue severity from a variety of medical and neurological disorders. Each item is rated on a Likert scale from 1-7. The total score is the sum of responses and ranges from 9-63, with higher scores indicating greater fatigue.	Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
Pittsburgh Sleep Quality Index (PSQI) Score	PSQI is a 19-item questionnaire that is routinely used in both clinical and research settings to assess sleep quality over the preceding one month. The total score ranges from 0-21, with higher scores reflecting worse sleep quality.	Baseline
Pittsburgh Sleep Quality Index (PSQI) Score	PSQI is a 19-item questionnaire that is routinely used in both clinical and research settings to assess sleep quality over the preceding one month. The total score ranges from 0-21, with higher scores reflecting worse sleep quality.	Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Rashmi Nisha Aurora, MD, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2024
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: March 8, 2024
• First Submitted That Met QC Criteria: March 8, 2024
• First Posted (Actual): March 15, 2024

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Wake Disorders; Apnea; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Amino Acids, Peptides, and Proteins; Sulfur Compounds; Organic Chemicals; Amino Acids; Cysteine; Amino Acids, Sulfur; Acetylcysteine; Therapeutics
• Other Study ID Numbers: 23-01469

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The de-identified participant data from the final research dataset used in the published manuscript will be shared upon reasonable request beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research provided the investigator who proposes to use the data executes a data use agreement with NYU Langone Health. Requests may be directed to: Rashmi.aurora@nyulangone.org. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research. Requests should be directed to Rashmi.aurora@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Access Criteria: The investigator who proposed to use the data will be granted access upon reasonable request.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No