N-acetylcysteine for Obstructive Sleep Apnea

Overseen By Rashmi Nisha Aurora, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: NYU Langone Health

Must not be taking: Opioids, Benzodiazepines, Antioxidants, others

Disqualifiers: Diabetes, Major sleep disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

206 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop all current medications, but you cannot participate if you use certain medications like diabetes drugs, opioids, benzodiazepines, or prescription sleep medications regularly. You also cannot have used N-acetylcysteine or certain antioxidants recently.

What evidence supports the effectiveness of the drug N-acetylcysteine for obstructive sleep apnea?

Research shows that N-acetylcysteine (NAC) is a well-tolerated antioxidant that helps reduce the risk of worsening symptoms in chronic obstructive pulmonary disease (COPD), which shares some characteristics with obstructive sleep apnea. This suggests potential benefits of NAC for respiratory conditions. ^{1 2 3 4 5}

Is N-acetylcysteine generally safe for humans?

N-acetylcysteine (NAC) is generally well-tolerated in humans, as shown in studies for conditions like chronic obstructive pulmonary disease (COPD). However, in premature infants with chronic lung disease, it may increase airway resistance and cause issues like bradycardia (slow heart rate) and cyanosis (bluish skin due to lack of oxygen). ^{1 3 4 6 7}

How is the drug N-acetylcysteine (NAC) unique for treating obstructive sleep apnea?

N-acetylcysteine (NAC) is unique for treating obstructive sleep apnea because it acts as an antioxidant and mucolytic (helps break down mucus), which may help reduce airway obstruction. Unlike other treatments, NAC is taken orally and has been studied for its potential to improve breathing by reducing mucus and inflammation. ^{1 2 4 5 7}

Research Team

Rashmi Nisha Aurora, MD

Principal Investigator

NYU Langone Health

Eligibility Criteria

This trial is for individuals with significant obstructive sleep apnea (OSA) who are already using standard treatment, positive airway pressure therapy (PAP). Participants should be interested in seeing if the supplement N-acetylcysteine (NAC) can reduce overnight oxidative stress and inflammation specific to their sex.

Inclusion Criteria

HbA1c <6.5%

Apnea-hypopnea index ≥15 events/hr on portable sleep monitoring

Exclusion Criteria

Current tobacco smoking

Shift work (i.e., working hours that routinely cause sleep initiation after 1:00 a.m.)

I have diabetes, as shown by my medication use or an HbA1c level of 6.5% or higher.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in

Participants undergo PAP therapy per standard clinical care

12 weeks

Treatment

Participants receive N-acetylcysteine (NAC) or placebo while continuing PAP therapy

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• N-acetylcysteine (NAC)

Trial Overview The study tests whether taking N-acetylcysteine (NAC) for four weeks has different effects on men and women with OSA, compared to a placebo. It's randomized, meaning participants are put into the NAC or placebo group by chance.

Participant Groups

Group I: Placebo Experimental Treatment 2 Interventions

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.

Group II: NAC Experimental Treatment 2 Interventions

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.

N-acetylcysteine (NAC) is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Acetadote for:

• Acetaminophen overdose
• Chronic bronchitis
• Cystic fibrosis
• Pneumonia
• Chronic obstructive pulmonary disease (COPD)
• Mucolytic agent

Approved in European Union as Fluimucil for:

• Symptomatic treatment of respiratory tract disorders associated with productive cough
• Chronic bronchitis
• Cystic fibrosis
• Pneumonia
• Chronic obstructive pulmonary disease (COPD)
• Mucolytic agent

Approved in Canada as Mucomyst for:

• Symptomatic treatment of respiratory tract disorders associated with productive cough
• Chronic bronchitis
• Cystic fibrosis
• Pneumonia
• Chronic obstructive pulmonary disease (COPD)
• Mucolytic agent

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Findings from Research

In a study of 20 patients with obstructive sleep apnoea syndrome (OSAS), those treated with N-acetylcysteine (NAC) showed significant improvements in sleep quality, including increased slow wave sleep and sleep efficiency, as well as reductions in apnoea-hypopnoea index and oxygen desaturation events after 30 days of treatment.

NAC also decreased markers of oxidative stress, suggesting it may help improve OSAS symptoms and potentially reduce reliance on continuous positive airway pressure therapy in the long term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-oxidant treatment in obstructive sleep apnoea syndrome. Sadasivam, K., Patial, K., Vijayan, VK., et al.[2011]

N-Acetylcysteine (NAC) has been shown to reduce pulmonary fibrosis in COPD by inhibiting the VWF/p38 MAPK signaling pathway, as demonstrated in a study involving 10 non-smokers and 10 smokers with COPD, along with COPD rat models.

NAC not only promotes immune response but also suppresses the epithelial-mesenchymal transformation (EMT) process, indicating its potential as a therapeutic target for alleviating COPD symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The antioxidant N-acetylcysteine promotes immune response and inhibits epithelial-mesenchymal transition to alleviate pulmonary fibrosis in chronic obstructive pulmonary disease by suppressing the VWF/p38 MAPK axis. Zhu, L., Xu, F., Kang, X., et al.[2022]

In a study involving 10 premature infants with chronic lung disease, intratracheal administration of N-acetylcysteine did not improve clinical status or pulmonary function, and was associated with increased airway resistance.

The treatment led to adverse effects, including bradycardia and cyanosis in some infants, indicating that N-acetylcysteine may not be safe or effective as a mucolytic agent in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intratracheal N-acetylcysteine use in infants with chronic lung disease. Bibi, H., Seifert, B., Oullette, M., et al.[2019]

N-acetylcysteine (NAC) significantly reduced the rate of healthcare resource utilization (HCU) events related to COPD exacerbations by 20% compared to placebo, with an even greater reduction of 23% in current and ex-smokers.

In patients using long-acting bronchodilators without inhaled corticosteroids (ICS), NAC led to a remarkable 60% reduction in exacerbation rates compared to those receiving placebo, suggesting NAC could be a beneficial alternative to ICS in certain COPD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of smoking status and concomitant medications on the effect of high-dose N-acetylcysteine on chronic obstructive pulmonary disease exacerbations: A post-hoc analysis of the PANTHEON study. Papi, A., Zheng, J., Criner, GJ., et al.[2020]

In a study involving 333 hospitalized patients with respiratory diseases, intravenous (IV) N-acetylcysteine (NAC) was found to be significantly more effective than placebo in reducing sputum viscosity and improving expectoration difficulty.

NAC was also shown to be non-inferior to ambroxol, a standard treatment, indicating that it is a viable alternative for patients needing mucolytic therapy, with a good safety profile and no new safety concerns identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous N-acetylcysteine in respiratory disease with abnormal mucus secretion. Tang, W., Zhu, D., Wu, F., et al.[2023]

The thioester prodrug A-1 of N-acetylcysteine (NAC) showed improved stability and bioavailability compared to NAC, with significant effects on reducing lung inflammation and improving lung function in a rat model of pulmonary inflammation.

By masking the thiol group, A-1 was odorless and demonstrated effective delivery of NAC at half the dose, suggesting that this prodrug strategy could enhance NAC's therapeutic potential while minimizing its drawbacks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Thioester Prodrug of N-acetylcysteine for Odor Masking and Bioavailability Enhancement. Bhilare, NV., Dhaneshwar, SS., Sinha, AJ., et al.[2019]

A study involving 46 healthy participants demonstrated that a new 2% oral N-acetylcysteine formulation is bioequivalent to an existing reference product, meaning they have similar pharmacokinetic profiles.

The new formulation was found to be safe and well tolerated, with most side effects being mild or moderate and not linked to the study drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, open-label, crossover study evaluating bioequivalence of two N-acetylcysteine 2% oral solution formulations in healthy subjects . Donath, F., Armogida, M., Shneyer, L.[2019]

References

1. India pubmed.ncbi.nlm.nih.gov

Anti-oxidant treatment in obstructive sleep apnoea syndrome. [2011]

2. England pubmed.ncbi.nlm.nih.gov

The antioxidant N-acetylcysteine promotes immune response and inhibits epithelial-mesenchymal transition to alleviate pulmonary fibrosis in chronic obstructive pulmonary disease by suppressing the VWF/p38 MAPK axis. [2022]

3. Norway pubmed.ncbi.nlm.nih.gov

Intratracheal N-acetylcysteine use in infants with chronic lung disease. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Impact of smoking status and concomitant medications on the effect of high-dose N-acetylcysteine on chronic obstructive pulmonary disease exacerbations: A post-hoc analysis of the PANTHEON study. [2020]

5. Italy pubmed.ncbi.nlm.nih.gov

Intravenous N-acetylcysteine in respiratory disease with abnormal mucus secretion. [2023]

6. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Novel Thioester Prodrug of N-acetylcysteine for Odor Masking and Bioavailability Enhancement. [2019]

7. Germany pubmed.ncbi.nlm.nih.gov

A randomized, open-label, crossover study evaluating bioequivalence of two N-acetylcysteine 2% oral solution formulations in healthy subjects . [2019]