Obstructive Sleep Apnea
Conditions
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.
Interventions
DIETARY_SUPPLEMENTN-acetylcysteine (NAC)
Participants will take two NAC 600mg capsules daily for four weeks.
DIETARY_SUPPLEMENTPlacebo
Participants will take two placebo 600mg capsules daily for four weeks.
All participants will receive PAP therapy per standard of care for OSA.
Sponsors
NYU Langone Health
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
55 Years to 75 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline | GSH measured using participant blood samples. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ratio of GSH to oxidized GSH (GSSG) (GSH:GSSG) | Baseline | GSH:GSSG measured using participant blood samples. |
| 8-Isoprostane Level | Baseline | 8-isoprostane levels measured using participant blood samples. |
| Plasma Nitrate Level | Baseline | Plasma nitrate levels measured using participant blood samples. |
| Plasma Nitrite Level | Baseline | Plasma nitrite levels measured using participant blood samples. |
| Organic Nitrite Level | Baseline | Organic nitrite levels measured using participant blood samples. |
| Interleukin 6 (IL-6) Level | Baseline | IL-6 levels measured using participant blood samples. |
| Tumor Necrosis Factor-alpha (TNFα) Receptor-1 (TNFα-R1) Level | Baseline | TNFα-R1 levels measured using participant blood samples. |
| Tumor Necrosis Factor-alpha (TNFα) Receptor-2 (TNFα-R2) Level | Baseline | TNFα-R2 levels measured using participant blood samples. |
| Reactive Hyperemia Index (RHI) Score | Baseline | 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 | Baseline | 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. |
| Insomnia Severity Index (ISI) Score | Baseline | 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). |
| Fatigue Severity Scale (FSS) Score | Baseline | 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. |
| Pittsburgh Sleep Quality Index (PSQI) Score | Baseline | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORRashmi Nisha Aurora, MD
NYU Langone Health
Outcome results
None listed