N-acetyl Cysteine for Idiopathic Pulmonary Fibrosis

(PRECISIONS Trial)

Recruiting at 25 trial locations

Overseen By Betsy Peters

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Weill Medical College of Cornell University

Must not be taking: NAC therapy

Disqualifiers: Pregnancy, Lung cancer, Liver failure, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

202 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to compare the effect of n-acetylcysteine (NAC) plus standard care with matched placebo plus standard of care in patients diagnosed with idiopathic pulmonary fibrosis (IPF) who have the TOLLIP rs3750920 TT genotype. The study will compare the time to a composite endpoint of relative decline in lung function \[10% relative decline in forced vital capacity (FVC), first respiratory hospitalization, lung transplantation, or all-cause mortality\] The secondary objectives will be to examine the effect of NAC on the components of the primary composite endpoint, the rates of clinical events, change in physiology, change in health status, and change in respiratory symptoms.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are taking pirfenidone or nintedanib, you must be on a stable dose for at least 6 weeks before joining the study.

What data supports the effectiveness of the drug N-acetyl cysteine for idiopathic pulmonary fibrosis?

Research shows that N-acetyl cysteine (NAC) can slow the decline of lung function in idiopathic pulmonary fibrosis (IPF) patients when used with other medications. It also helps increase glutathione levels, an important antioxidant, in the lungs of IPF patients, which may enhance lung protection. ^{1 2 3 4 5}

Is N-acetylcysteine safe for humans?

N-acetylcysteine (NAC) is generally considered safe for humans, with low toxicity and rare adverse effects, even when used with other treatments. In studies involving patients with idiopathic pulmonary fibrosis and other chronic respiratory diseases, no significant adverse effects were noted. ^{1 2 4 6 7}

How does the drug N-acetyl cysteine work for idiopathic pulmonary fibrosis?

N-acetyl cysteine (NAC) is unique for idiopathic pulmonary fibrosis (IPF) because it acts as an antioxidant, helping to slow lung function decline by increasing glutathione levels, a key antioxidant in the lungs. It can be administered through inhalation or intravenously, offering flexibility in treatment options. ^{1 2 4 5 8}

Research Team

Fernando J Martinez, MD

Principal Investigator

Weill Medical College of Cornell University

Imre Noth, MD

Principal Investigator

University of Virginia

Cathie Spino, ScD

Principal Investigator

University of Michigan

Kevin Flaherty, MS, MD

Principal Investigator

University of Michigan

Eligibility Criteria

This trial is for adults over 40 with idiopathic pulmonary fibrosis (IPF) who have a specific genetic marker (TOLLIP rs3750920 TT genotype). They must be on a stable dose of certain IPF medications if used, and able to give informed consent. Pregnant women, those planning pregnancy or not using effective contraception are excluded, as well as individuals with severe illnesses or recent use of investigational drugs.

Inclusion Criteria

I have been on a stable dose of pirfenidone or nintedanib for at least 6 weeks.

Signed informed consent

I am 40 years old or older.

Exclusion Criteria

Your lung function test shows that you have less than 45% of the expected breathing capacity.

I have not had a respiratory infection treated with antibiotics in the last 4 weeks.

I am on the lung transplant list.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 600 mg oral N-acetylcysteine (NAC) or placebo three times daily for 24 months

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• N-acetyl cysteine
• Placebo

Trial Overview The PRECISIONS trial is testing whether N-acetylcysteine (NAC), added to standard care for IPF patients with a particular genotype, can slow down lung function decline compared to placebo. It will also look at hospitalization rates, transplant needs, survival rates, changes in respiratory symptoms and overall health status.

Participant Groups

Group I: N-acetylcysteine Experimental Treatment 1 Intervention

600 mg oral N-acetylcysteine (NAC) three times daily for 24 months.

Group II: Placebo Placebo Group 1 Intervention

Placebo tablet three times daily for 24 months.

N-acetyl cysteine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Acetylcysteine for:

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

Approved in European Union as Acetylcysteine for:

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

Approved in Canada as Acetylcysteine for:

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

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

University of Washington

Collaborator

Trials

1,858

Recruited

2,023,000+

Pulmonary Fibrosis Foundation

Collaborator

Trials

8

Recruited

12,600+

Three Lakes Foundation

Collaborator

Trials

1

Recruited

200+

University of Michigan

Collaborator

Trials

1,891

Recruited

6,458,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

University of Virginia

Collaborator

Trials

802

Recruited

1,342,000+

Findings from Research

N-acetylcysteine (NAC) can significantly reduce the production of inflammatory markers like TNF-alpha and TGF-beta1 in alveolar macrophages from patients with idiopathic pulmonary fibrosis (IPF), suggesting its potential as an anti-inflammatory treatment.

In a study involving 16 IPF patients, NAC demonstrated a dose-dependent effect, with the highest concentration (10 mM) leading to substantial suppression of both spontaneous and LPS-stimulated inflammatory responses, indicating its possible role in slowing disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-acetylcysteine inhibits TNF-alpha, sTNFR, and TGF-beta1 release by alveolar macrophages in idiopathic pulmonary fibrosis in vitro. Cu, A., Ye, Q., Sarria, R., et al.[2016]

N-acetylcysteine (NAC) is effective as a mucolytic agent in cystic fibrosis and serves as a safe antidote for acetaminophen overdose, demonstrating its versatility in treating respiratory conditions.

Due to its antioxidative and anti-inflammatory properties, NAC may benefit patients with chronic respiratory diseases like COPD and asthma, with low toxicity and rare side effects, making it a cost-effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in the Use of N-Acetylcysteine in Chronic Respiratory Diseases. Mokra, D., Mokry, J., Barosova, R., et al.[2023]

References

1. Italy pubmed.ncbi.nlm.nih.gov

N-acetylcysteine inhibits TNF-alpha, sTNFR, and TGF-beta1 release by alveolar macrophages in idiopathic pulmonary fibrosis in vitro. [2016]

2. United States pubmed.ncbi.nlm.nih.gov

Intravenous N-acetylcysteine and lung glutathione of patients with pulmonary fibrosis and normals. [2013]

3. England pubmed.ncbi.nlm.nih.gov

The effect of oral N-acetylcysteine on lung glutathione levels in idiopathic pulmonary fibrosis. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Advances in the Use of N-Acetylcysteine in Chronic Respiratory Diseases. [2023]

5. Iran pubmed.ncbi.nlm.nih.gov

N-Acetylcysteine attenuated pulmonary fibrosis induced by bleomycin via immunomodulation responses. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Efficacy of N-Acetylcysteine in Idiopathic Pulmonary Fibrosis: A Systematic Review and Meta-Analysis. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Multifaceted activity of N-acetyl-l-cysteine in chronic obstructive pulmonary disease. [2019]

8. Japan pubmed.ncbi.nlm.nih.gov

Long-term efficacy of inhaled N-acetylcysteine in patients with idiopathic pulmonary fibrosis. [2019]