N-acetyl Cysteine for Idiopathic Pulmonary Fibrosis

(PRECISIONS Trial)

Not currently recruiting at 25 trial locations

Overseen By Betsy Peters

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Fernando J Martinez

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether n-acetylcysteine (NAC) can aid individuals with idiopathic pulmonary fibrosis (IPF), a lung disease that makes breathing difficult. Researchers aim to determine if NAC, combined with standard care, can slow lung function decline compared to a placebo (a pill with no active medicine). Individuals with a specific genetic profile (TOLLIP rs3750920 TT genotype) and an IPF diagnosis might be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Research has shown that n-acetylcysteine (NAC) is usually safe for patients. In one study, participants reported that NAC was safe and easy to handle, with most experiencing no serious side effects. However, other studies have found that NAC may not be very effective for idiopathic pulmonary fibrosis (IPF), a lung disease. While researchers are testing NAC again, current evidence suggests it is safe but might not improve lung function in these patients. This information can help prospective trial participants weigh the benefits and risks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for idiopathic pulmonary fibrosis, which often include antifibrotic medications like nintedanib and pirfenidone, N-acetyl cysteine (NAC) offers a unique approach. NAC is an antioxidant that may help reduce lung damage by replenishing glutathione levels, a powerful antioxidant in the body. Researchers are excited about NAC because it targets oxidative stress, which is believed to play a crucial role in the progression of lung scarring. This could potentially slow down disease progression in a different, complementary way to existing therapies.

What evidence suggests that N-acetyl cysteine might be an effective treatment for idiopathic pulmonary fibrosis?

Research has shown that N-acetylcysteine (NAC), which participants in this trial may receive, may help people with idiopathic pulmonary fibrosis (IPF) by slowing lung damage. One study found that NAC reduced the decline in lung function, measured by how much air a person can exhale. Another study found that NAC helped people walk longer distances in a 6-minute test, indicating better exercise ability. While NAC is not a cure, these findings suggest it may help manage IPF symptoms and slow its progression, especially for those with a specific genetic type called TOLLIP rs3750920 TT. ^{4 6 7 8 9}

Who Is on the Research Team?

Cathie Spino, ScD

Principal Investigator

University of Michigan

Fernando J Martinez, MD

Principal Investigator

University of Massachusetts Chan Medical School

Imre Noth, MD

Principal Investigator

University of Virginia

Kevin Flaherty, MS, MD

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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?

Fernando J Martinez

Lead Sponsor

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+

Published Research Related to This Trial

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4902516/

Efficacy of N-Acetylcysteine in Idiopathic Pulmonary Fibrosis N-acetylcysteine was found to have a significant effect only on decreases in percentage of predicted vital capacity and 6 minutes walking test distance.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04300920

NCT04300920 | Prospective Treatment Efficacy in IPF ... 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 ...

3. bmcpulmmed.biomedcentral.com bmcpulmmed.biomedcentral.com/articles/10.1186/s12890-022-02281-8

Design and rationale for the prospective treatment efficacy in ... Patients with idiopathic pulmonary fibrosis (IPF) that have the TOLLIP rs3750920 TT genotype will exhibit improved clinical outcomes when ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa042976

High-Dose Acetylcysteine in Idiopathic Pulmonary Fibrosis We conducted a double-blind, randomized, placebo-controlled multicenter study that assessed the effectiveness over one year of a high oral dose ...

5. spandidos-publications.com spandidos-publications.com/10.3892/etm.2019.7579

Efficacy and safety of N‑acetylcysteine therapy for ... NAC therapy reduced the decline in lung function, as indicated by the FVC and DLCO, and slowed the progression of the disease, as indicated by the PaO2.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6566037/

Efficacy and safety of N-acetylcysteine therapy for ... These results suggest good efficacy, tolerability and safety of the treatment. Furthermore, subgroup analysis revealed that combined therapy ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03720483

NCT03720483 | Inhaled NAC in Treatment of IPF This study plans to learn more about the safety and tolerability of inhaled N-Acetylcysteine (NAC) in patients with pulmonary fibrosis. The study will also ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4116664/

Randomized Trial of N-acetylcysteine in Idiopathic Pulmonary ... Conclusions. Compared to placebo NAC offered no benefit for the preservation of FVC in IPF patients with mild-to-moderate physiological abnormalities.

9. thelancet.com thelancet.com/journals/lanres/article/PIIS2213-2600%2816%2930327-7/fulltext

N-acetylcysteine for idiopathic pulmonary fibrosis an overall strong negative tone for using N-acetylcysteine is evident and use of N-acetylcysteine in patients with idiopathic pulmonary fibrosis is discouraged.