Clinical trial NCT06311045: Obstructive Sleep Apnea (OSA) and Sex-Specific Responses to N-acetylcysteine (NAC)
Official title: Basis of Sex-specific Therapeutic Responses to Obstructive Sleep Apnea (OSA): a Trial of N-acetylcysteine (NAC) in Obstructive Sleep Apnea (OSA)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Obstructive Sleep Apnea
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2024-03-15
Enrollment: 206
Sex: ALL
Minimum age (years): 55
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Percent Change in Overnight Levels of Glutathione (GSH)
timeFrame: Baseline, Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
measure: Mean Change in Pre- to Post-Sleep GSH Levels
timeFrame: Baseline
measure: Mean Change in Pre- to Post-Sleep GSH Levels
timeFrame: Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
Secondary outcomes:
measure: Ratio of GSH to oxidized GSH (GSSG) (GSH:GSSG)
timeFrame: Baseline
measure: Ratio of GSH to oxidized GSH (GSSG) (GSH:GSSG)
timeFrame: Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
measure: 8-Isoprostane Level
timeFrame: Baseline
measure: 8-Isoprostane Level
timeFrame: Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
measure: Plasma Nitrate Level
timeFrame: Baseline
measure: Plasma Nitrate Level
timeFrame: Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
measure: Plasma Nitrite Level
timeFrame: Baseline
measure: Plasma Nitrite Level
timeFrame: Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
measure: Organic Nitrite Level
timeFrame: Baseline
measure: Organic Nitrite Level
timeFrame: Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
measure: Interleukin 6 (IL-6) Level
timeFrame: Baseline
measure: Interleukin 6 (IL-6) Level
timeFrame: Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
measure: Tumor Necrosis Factor-alpha (TNFα) Receptor-1 (TNFα-R1) Level
timeFrame: Baseline
measure: Tumor Necrosis Factor-alpha (TNFα) Receptor-1 (TNFα-R1) Level
timeFrame: Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
measure: Tumor Necrosis Factor-alpha (TNFα) Receptor-2 (TNFα-R2) Level
timeFrame: Baseline
measure: Tumor Necrosis Factor-alpha (TNFα) Receptor-2 (TNFα-R2) Level
timeFrame: Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
measure: Reactive Hyperemia Index (RHI) Score
timeFrame: Baseline
measure: Reactive Hyperemia Index (RHI) Score
timeFrame: Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
measure: Epworth Sleepiness Scale (ESS) Score
timeFrame: Baseline
measure: Epworth Sleepiness Scale (ESS) Score
timeFrame: Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
measure: Insomnia Severity Index (ISI) Score
timeFrame: Baseline
measure: Insomnia Severity Index (ISI) Score
timeFrame: Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
measure: Fatigue Severity Scale (FSS) Score
timeFrame: Baseline
measure: Fatigue Severity Scale (FSS) Score
timeFrame: Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
measure: Pittsburgh Sleep Quality Index (PSQI) Score
timeFrame: Baseline
measure: Pittsburgh Sleep Quality Index (PSQI) Score
timeFrame: Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
Other outcomes:
Locations:
city: New York
country: United States
facility: NYU Langone Health
state: New York
Study officials:
affiliation: NYU Langone Health
name: Rashmi Nisha Aurora, MD
role: PRINCIPAL_INVESTIGATOR
References: