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

Obstructive Sleep Apnea Clinical Trial

Official title:

Basis of Sex-specific Therapeutic Responses to Obstructive Sleep Apnea (OSA): a Trial of N-acetylcysteine (NAC) in Obstructive Sleep Apnea (OSA)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06311045
• Other study ID #: 23-01469
• Status: Not yet recruiting
• Phase: N/A
• Start date: April 2024
• Est. completion date: December 2028

Study information

• Verified date: March 2024
• Source: NYU Langone Health
• Contact: Rashmi Nisha Aurora, MD
• Phone: 443-513-6535
• Email: Rashmi.aurora[@]nyulangone.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 206
• Est. completion date: December 2028
• Est. primary completion date: June 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Apnea
• Obstructive Sleep Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

Dietary Supplement:
• N-acetylcysteine (NAC)
Participants will take two NAC 600mg capsules daily for four weeks.
• Placebo
Participants will take two placebo 600mg capsules daily for four weeks.

Procedure:
• Positive Airway Pressure (PAP) Therapy
All participants will receive PAP therapy per standard of care for OSA.

Locations

Country	Name	City	State
United States	NYU Langone Health	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
NYU Langone Health	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change in Overnight Levels of Glutathione (GSH)	GSH measured using participant blood samples.	Baseline, Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
Primary	Mean Change in Pre- to Post-Sleep GSH Levels	GSH measured using participant blood samples.	Baseline
Primary	Mean Change in Pre- to Post-Sleep GSH Levels	GSH measured using participant blood samples.	Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
Secondary	Ratio of GSH to oxidized GSH (GSSG) (GSH:GSSG)	GSH:GSSG measured using participant blood samples.	Baseline
Secondary	Ratio of GSH to oxidized GSH (GSSG) (GSH:GSSG)	GSH:GSSG measured using participant blood samples.	Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
Secondary	8-Isoprostane Level	8-isoprostane levels measured using participant blood samples.	Baseline
Secondary	8-Isoprostane Level	8-isoprostane levels measured using participant blood samples.	Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
Secondary	Plasma Nitrate Level	Plasma nitrate levels measured using participant blood samples.	Baseline
Secondary	Plasma Nitrate Level	Plasma nitrate levels measured using participant blood samples.	Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
Secondary	Plasma Nitrite Level	Plasma nitrite levels measured using participant blood samples.	Baseline
Secondary	Plasma Nitrite Level	Plasma nitrite levels measured using participant blood samples.	Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
Secondary	Organic Nitrite Level	Organic nitrite levels measured using participant blood samples.	Baseline
Secondary	Organic Nitrite Level	Organic nitrite levels measured using participant blood samples.	Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
Secondary	Interleukin 6 (IL-6) Level	IL-6 levels measured using participant blood samples.	Baseline
Secondary	Interleukin 6 (IL-6) Level	IL-6 levels measured using participant blood samples.	Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
Secondary	Tumor Necrosis Factor-alpha (TNFa) Receptor-1 (TNFa-R1) Level	TNFa-R1 levels measured using participant blood samples.	Baseline
Secondary	Tumor Necrosis Factor-alpha (TNFa) Receptor-1 (TNFa-R1) Level	TNFa-R1 levels measured using participant blood samples.	Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
Secondary	Tumor Necrosis Factor-alpha (TNFa) Receptor-2 (TNFa-R2) Level	TNFa-R2 levels measured using participant blood samples.	Baseline
Secondary	Tumor Necrosis Factor-alpha (TNFa) Receptor-2 (TNFa-R2) Level	TNFa-R2 levels measured using participant blood samples.	Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
Secondary	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.	Baseline
Secondary	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.	Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
Secondary	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.	Baseline
Secondary	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.	Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
Secondary	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).	Baseline
Secondary	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 (22-28).	Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
Secondary	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.	Baseline
Secondary	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.	Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)
Secondary	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.	Baseline
Secondary	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.	Final Study Visit (4 Weeks post Initiation of Study Therapy; up to Month 6)