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

N/AActive Not RecruitingNCT06311045

NYU Langone Health14 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

DOUBLE

Enrollment

Conditions

Obstructive Sleep Apnea

Interventions

N-acetylcysteine (NAC)DIETARY_SUPPLEMENT

Participants will take two NAC 600mg capsules daily for four weeks.

PlaceboDIETARY_SUPPLEMENT

Participants will take two placebo 600mg capsules daily for four weeks.

Positive Airway Pressure (PAP) TherapyPROCEDURE

All participants will receive PAP therapy per standard of care for OSA.

Eligibility

Sex: ALLMin age: 55 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Locations (1)

NYU Langone Health

New York, New York, United States

Outcomes

Primary Outcomes

Percent Change in Overnight Levels of Glutathione (GSH)

GSH measured using participant blood samples.

Time frame: 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.

Time frame: Baseline

Mean Change in Pre- to Post-Sleep GSH Levels

GSH measured using participant blood samples.

Time frame: Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)

Secondary Outcomes

Ratio of GSH to oxidized GSH (GSSG) (GSH:GSSG)

GSH:GSSG measured using participant blood samples.

Time frame: Baseline

Ratio of GSH to oxidized GSH (GSSG) (GSH:GSSG)

GSH:GSSG measured using participant blood samples.

Time frame: 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.

Time frame: Baseline

8-Isoprostane Level

8-isoprostane levels measured using participant blood samples.

Time frame: 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.

Data from ClinicalTrials.gov

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Time frame: Baseline

Plasma Nitrate Level

Plasma nitrate levels measured using participant blood samples.

Time frame: 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.

Time frame: Baseline

Plasma Nitrite Level

Plasma nitrite levels measured using participant blood samples.

Time frame: 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.

Time frame: Baseline

Organic Nitrite Level

Organic nitrite levels measured using participant blood samples.

Time frame: 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.

Time frame: Baseline

Interleukin 6 (IL-6) Level

IL-6 levels measured using participant blood samples.

Time frame: 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.

Time frame: Baseline

Tumor Necrosis Factor-alpha (TNFα) Receptor-1 (TNFα-R1) Level

TNFα-R1 levels measured using participant blood samples.

Time frame: 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.

Time frame: Baseline

Tumor Necrosis Factor-alpha (TNFα) Receptor-2 (TNFα-R2) Level

TNFα-R2 levels measured using participant blood samples.

Time frame: 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.

Time frame: Baseline

Reactive Hyperemia Index (RHI) Score

Time frame: 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.

Time frame: Baseline

Epworth Sleepiness Scale (ESS) Score

Time frame: 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).

Time frame: Baseline

Insomnia Severity Index (ISI) Score

Time frame: 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.

Time frame: Baseline

Fatigue Severity Scale (FSS) Score

Time frame: 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.

Time frame: Baseline

Pittsburgh Sleep Quality Index (PSQI) Score

Time frame: Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)