Basis of Sex-specific Therapeutic Responses to Obstructive Sleep Apnea (OSA): a Trial of N-acetylcysteine (NAC) in Obstructive Sleep Apnea (OSA)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Active, not recruiting
- Sponsor
- NYU Langone Health
- Enrollment
- 14
- Locations
- 1
- Primary Endpoint
- Percent Change in Overnight Levels of Glutathione (GSH)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Other
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 55 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
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.
Intervention: Placebo (Dietary Supplement)
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.
Intervention: N-acetylcysteine (NAC) (Dietary Supplement)
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.
Intervention: Positive Airway Pressure (PAP) Therapy (Procedure)
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.
Intervention: Positive Airway Pressure (PAP) Therapy (Procedure)
Outcomes
Primary Outcomes
Percent Change in Overnight Levels of Glutathione (GSH)
Time Frame: 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
Time Frame: 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
Time Frame: Baseline
GSH measured using participant blood samples.
Secondary Outcomes
- Ratio of GSH to oxidized GSH (GSSG) (GSH:GSSG)(Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6))
- 8-Isoprostane Level(Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6))
- Organic Nitrite Level(Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6))
- Tumor Necrosis Factor-alpha (TNFα) Receptor-1 (TNFα-R1) Level(Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6))
- Interleukin 6 (IL-6) Level(Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6))
- Plasma Nitrate Level(Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6))
- Plasma Nitrite Level(Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6))
- Tumor Necrosis Factor-alpha (TNFα) Receptor-2 (TNFα-R2) Level(Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6))
- Reactive Hyperemia Index (RHI) Score(Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6))
- Epworth Sleepiness Scale (ESS) Score(Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6))
- Pittsburgh Sleep Quality Index (PSQI) Score(Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6))
- Insomnia Severity Index (ISI) Score(Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6))
- Fatigue Severity Scale (FSS) Score(Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6))
- Organic Nitrite Level(Baseline)
- Interleukin 6 (IL-6) Level(Baseline)
- Ratio of GSH to oxidized GSH (GSSG) (GSH:GSSG)(Baseline)
- 8-Isoprostane Level(Baseline)
- Plasma Nitrate Level(Baseline)
- Plasma Nitrite Level(Baseline)
- Tumor Necrosis Factor-alpha (TNFα) Receptor-1 (TNFα-R1) Level(Baseline)
- Tumor Necrosis Factor-alpha (TNFα) Receptor-2 (TNFα-R2) Level(Baseline)
- Reactive Hyperemia Index (RHI) Score(Baseline)
- Epworth Sleepiness Scale (ESS) Score(Baseline)
- Insomnia Severity Index (ISI) Score(Baseline)
- Fatigue Severity Scale (FSS) Score(Baseline)
- Pittsburgh Sleep Quality Index (PSQI) Score(Baseline)