Obstructive Sleep Apnea (OSA) and Sex-Specific Responses to N-acetylcysteine (NAC)
- Conditions
- Obstructive Sleep Apnea
- Interventions
- Dietary Supplement: PlaceboDietary Supplement: N-acetylcysteine (NAC)Procedure: Positive Airway Pressure (PAP) Therapy
- Registration Number
- NCT06311045
- Lead Sponsor
- NYU Langone Health
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 206
- Apnea-hypopnea index ≥15 events/hr on portable sleep monitoring
- HbA1c <6.5%
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo 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. NAC Positive Airway Pressure (PAP) Therapy 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. NAC N-acetylcysteine (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. Placebo Positive Airway Pressure (PAP) Therapy 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.
- Primary Outcome Measures
Name Time Method Percent Change in Overnight Levels of Glutathione (GSH) Baseline, Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6) GSH measured using participant blood samples.
Mean Change in Pre- to Post-Sleep GSH Levels Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6) GSH measured using participant blood samples.
- Secondary Outcome Measures
Name Time Method Ratio of GSH to oxidized GSH (GSSG) (GSH:GSSG) Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6) GSH:GSSG measured using participant blood samples.
8-Isoprostane Level Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6) 8-isoprostane levels measured using participant blood samples.
Organic Nitrite Level Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6) Organic nitrite levels measured using participant blood samples.
Tumor Necrosis Factor-alpha (TNFα) Receptor-1 (TNFα-R1) Level Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6) TNFα-R1 levels measured using participant blood samples.
Interleukin 6 (IL-6) Level Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6) IL-6 levels measured using participant blood samples.
Plasma Nitrate Level Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6) Plasma nitrate levels measured using participant blood samples.
Plasma Nitrite Level Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6) Plasma nitrite levels measured using participant blood samples.
Tumor Necrosis Factor-alpha (TNFα) Receptor-2 (TNFα-R2) Level Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6) TNFα-R2 levels measured using participant blood samples.
Reactive Hyperemia Index (RHI) Score Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6) 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.
Epworth Sleepiness Scale (ESS) Score Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6) 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.
Pittsburgh Sleep Quality Index (PSQI) Score Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6) 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.
Insomnia Severity Index (ISI) Score Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6) 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).
Fatigue Severity Scale (FSS) Score Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6) 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.
Trial Locations
- Locations (1)
NYU Langone Health
🇺🇸New York, New York, United States