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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the supplement N-acetylcysteine (NAC) can alleviate obstructive sleep apnea (OSA) by reducing stress, inflammation, and blood vessel issues during sleep. Participants will receive either NAC or a placebo while continuing their standard positive airway pressure therapy. The study seeks individuals with significant OSA affecting breathing during sleep, excluding those with diabetes or other major sleep disorders. As an unphased trial, participants can contribute to groundbreaking research that may enhance future OSA treatments.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that N-acetylcysteine (NAC) is generally safe for most adults. The FDA has approved it for lung issues and as a treatment for acetaminophen overdose. Studies have found that taking NAC orally, particularly at a dose of 600 mg daily, is well-tolerated in individuals with breathing problems, with few side effects reported. While some side effects can occur, they are usually mild. This makes NAC a promising option for those considering participation in a trial for obstructive sleep apnea. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard treatments for obstructive sleep apnea, which often rely on continuous positive airway pressure (PAP) machines, N-acetylcysteine (NAC) brings a fresh approach. NAC is an antioxidant known for reducing oxidative stress and inflammation, which might help alleviate symptoms of sleep apnea. Researchers are excited about NAC because it could offer a non-invasive, supplementary option to enhance current therapies, potentially improving patient comfort and adherence.

What evidence suggests that N-acetylcysteine might be an effective treatment for obstructive sleep apnea?

Research has shown that N-acetylcysteine (NAC), which participants in this trial may receive, might help people with obstructive sleep apnea (OSA). In a study with 20 individuals with OSA, those who took NAC experienced improved sleep quality. NAC reduces damage and swelling in the body, potentially alleviating OSA symptoms by addressing stress and inflammation. Although more research is needed, these early results suggest NAC could be a helpful supplement for people with OSA. ^{4 6 7 8 9}

Who Is on the Research Team?

Rashmi Nisha Aurora, MD

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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) 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 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]

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]

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]

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]

Citations

1. atsjournals.org atsjournals.org/doi/10.1164/rccm.201308-1555rr

High-Dose N-Acetylcysteine in Chronic Obstructive ... Oral N-acetylcysteine (NAC) has been proposed as adjunctive COPD therapy, given its antioxidant, antiinflammatory, and mucolytic effects.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06311045

NCT06311045 | Obstructive Sleep Apnea (OSA) and Sex- ... 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8211525/

N-Acetylcysteine: A Review of Clinical Usefulness (an Old ... N-acetylcysteine may be useful as an adjuvant in treating various medical conditions, especially chronic diseases.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10526097/

Advances in the Use of N-Acetylcysteine in Chronic ... This article brings a review of information on the mechanisms of inflammation and oxidative stress in selected chronic respiratory diseases and discusses the ...

5. withpower.com withpower.com/trial/phase-sleep-apnea-obstructive-3-2024-4763b

N-acetylcysteine for Obstructive Sleep Apnea In a study of 20 patients with obstructive sleep apnoea syndrome (OSAS), those treated with N-acetylcysteine (NAC) showed significant improvements in sleep ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7892733/

Safety of N-Acetylcysteine at High Doses in Chronic ... Thus, the safety data on oral NAC 600 mg daily in respiratory disease showed that the treatment is well tolerated and the adverse events ...

7. go.drugbank.com go.drugbank.com/drugs/DB06151

Acetylcysteine: Uses, Interactions, Mechanism of Action Acetylcysteine is a medication that can be used as a mucolytic in patients with certain lung conditions and as an antidote for acetaminophen overdose.

8. webmd.com webmd.com/vitamins/ai/ingredientmono-1018/n-acetyl-cysteine-nac/

N-Acetyl Cysteine (Nac) – Uses, Side Effects, and More When taken by mouth: N-acetyl cysteine is likely safe for most adults. N-acetyl cysteine is an FDA-approved prescription drug. It can cause side effects such as ...

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2006/021539s004lbl.pdf

Acetadote (acetylcysteine) Injection Package Insert Evaluable data were available from a total of 148 pediatric patients (less than 16 years of age) who were admitted for poisoning following ...