Obstructive Sleep Apnea (OSA) and Sex-Specific Responses to N-acetylcysteine (NAC)
Basis of Sex-specific Therapeutic Responses to Obstructive Sleep Apnea (OSA): a Trial of N-acetylcysteine (NAC) in Obstructive Sleep Apnea (OSA)
Study Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Study Type
Study Type
Enrollment (Actual)
Enrollment
Phase
Phase
- Not Applicable
Contacts and Locations
Study Contact
Study Contact
- Name: Rashmi Nisha Aurora, MD
- Phone Number: 443-513-6535
- Email: Rashmi.aurora@nyulangone.org
Study Contact Backup
- Name: Ariana Budhu
- Phone Number: 646-501-0617
- Email: Ariana.budhu@nyulangone.org
Study Locations
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New York
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New York, New York, United States, 10016
- NYU Langone Health
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-
Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Number of Arms
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
|---|---|
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Experimental: 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.
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Participants will take two NAC 600mg capsules daily for four weeks.
All participants will receive PAP therapy per standard of care for OSA.
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Experimental: 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.
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All participants will receive PAP therapy per standard of care for OSA.
Participants will take two placebo 600mg capsules daily for four weeks.
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What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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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)
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GSH measured using participant blood samples.
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Baseline, Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
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Mean Change in Pre- to Post-Sleep GSH Levels
Time Frame: Baseline
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GSH measured using participant blood samples.
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Baseline
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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)
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GSH measured using participant blood samples.
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Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
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Secondary Outcome Measures
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Ratio of GSH to oxidized GSH (GSSG) (GSH:GSSG)
Time Frame: Baseline
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GSH:GSSG measured using participant blood samples.
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Baseline
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Ratio of GSH to oxidized GSH (GSSG) (GSH:GSSG)
Time Frame: Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
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GSH:GSSG measured using participant blood samples.
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Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
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8-Isoprostane Level
Time Frame: Baseline
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8-isoprostane levels measured using participant blood samples.
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Baseline
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8-Isoprostane Level
Time Frame: Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
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8-isoprostane levels measured using participant blood samples.
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Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
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Plasma Nitrate Level
Time Frame: Baseline
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Plasma nitrate levels measured using participant blood samples.
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Baseline
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Plasma Nitrate Level
Time Frame: Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
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Plasma nitrate levels measured using participant blood samples.
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Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
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Plasma Nitrite Level
Time Frame: Baseline
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Plasma nitrite levels measured using participant blood samples.
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Baseline
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Plasma Nitrite Level
Time Frame: Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
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Plasma nitrite levels measured using participant blood samples.
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Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
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Organic Nitrite Level
Time Frame: Baseline
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Organic nitrite levels measured using participant blood samples.
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Baseline
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Organic Nitrite Level
Time Frame: Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
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Organic nitrite levels measured using participant blood samples.
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Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
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Interleukin 6 (IL-6) Level
Time Frame: Baseline
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IL-6 levels measured using participant blood samples.
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Baseline
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Interleukin 6 (IL-6) Level
Time Frame: Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
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IL-6 levels measured using participant blood samples.
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Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
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Tumor Necrosis Factor-alpha (TNFα) Receptor-1 (TNFα-R1) Level
Time Frame: Baseline
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TNFα-R1 levels measured using participant blood samples.
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Baseline
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Tumor Necrosis Factor-alpha (TNFα) Receptor-1 (TNFα-R1) Level
Time Frame: Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
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TNFα-R1 levels measured using participant blood samples.
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Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
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Tumor Necrosis Factor-alpha (TNFα) Receptor-2 (TNFα-R2) Level
Time Frame: Baseline
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TNFα-R2 levels measured using participant blood samples.
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Baseline
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Tumor Necrosis Factor-alpha (TNFα) Receptor-2 (TNFα-R2) Level
Time Frame: Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
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TNFα-R2 levels measured using participant blood samples.
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Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
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Reactive Hyperemia Index (RHI) Score
Time Frame: Baseline
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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.
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Baseline
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Reactive Hyperemia Index (RHI) Score
Time Frame: Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
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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.
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Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
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Epworth Sleepiness Scale (ESS) Score
Time Frame: Baseline
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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.
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Baseline
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Epworth Sleepiness Scale (ESS) Score
Time Frame: Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
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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.
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Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
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Insomnia Severity Index (ISI) Score
Time Frame: Baseline
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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).
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Baseline
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Insomnia Severity Index (ISI) Score
Time Frame: Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
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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).
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Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
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Fatigue Severity Scale (FSS) Score
Time Frame: Baseline
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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.
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Baseline
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Fatigue Severity Scale (FSS) Score
Time Frame: Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
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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.
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Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
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Pittsburgh Sleep Quality Index (PSQI) Score
Time Frame: Baseline
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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.
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Baseline
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Pittsburgh Sleep Quality Index (PSQI) Score
Time Frame: Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
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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.
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Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
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Collaborators and Investigators
Sponsor
Sponsor
Collaborators
Collaborators
Investigators
Investigators
- Principal Investigator: Rashmi Nisha Aurora, MD, NYU Langone Health
Study record dates
Study Major Dates
Study Start (Actual)
Study Start
Primary Completion (Estimated)
Primary Completion
Study Completion (Estimated)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (Actual)
First Posted
Study Record Updates
Last Update Posted (Actual)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Nervous System Diseases
- Respiratory Tract Diseases
- Respiration Disorders
- Sleep Wake Disorders
- Apnea
- Sleep Disorders, Intrinsic
- Dyssomnias
- Sleep Apnea Syndromes
- Sleep Apnea, Obstructive
- Amino Acids, Peptides, and Proteins
- Sulfur Compounds
- Organic Chemicals
- Amino Acids
- Cysteine
- Amino Acids, Sulfur
- Acetylcysteine
- Therapeutics
Other Study ID Numbers
Other Study ID Numbers
- 23-01469
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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