N-acetylcysteine for Retinitis Pigmentosa

(NAC Attack Trial)

Not currently recruiting at 35 trial locations

Overseen By David Birch

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Johns Hopkins University

Disqualifiers: Active cancer, Renal failure, Liver disease, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 45 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether N-acetylcysteine (NAC) can slow vision loss in people with retinitis pigmentosa (RP). RP is a genetic condition that causes night blindness and eventually tunnel vision. NAC may protect the eye from further damage. Participants will take either NAC or a placebo (a pill with no active ingredient) to determine if NAC is effective. This trial suits those with RP experiencing night vision issues and narrowing vision fields. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for RP.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot take supplements other than vitamin A, and your blood pressure must be controlled if you are on antihypertensive medication.

Is there any evidence suggesting that N-acetylcysteine is likely to be safe for humans?

A previous study found that taking oral N-acetylcysteine (NAC) was safe and well-tolerated by people with retinitis pigmentosa (RP). This research suggested that NAC might improve certain aspects of vision. Another study confirmed that NAC is generally safe for long-term use. NAC reduces oxidative stress, a type of cell damage, which might help protect vision. Overall, current findings indicate that NAC appears safe for people with RP. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for retinitis pigmentosa?

Unlike the standard treatments for retinitis pigmentosa, which often focus on slowing vision loss through supplements or gene therapy, N-acetylcysteine (NAC) offers a fresh approach. NAC is unique because it aims to protect the retina by acting as an antioxidant, potentially reducing oxidative stress that contributes to cell damage. Researchers are excited about NAC because its antioxidant properties could offer a new layer of defense, possibly preserving vision more effectively than current options. This new mechanism of action sets it apart and brings hope for better management of this progressive eye condition.

What evidence suggests that N-acetylcysteine might be an effective treatment for retinitis pigmentosa?

Research shows that N-acetylcysteine (NAC), which participants in this trial may receive, might help improve vision in people with retinitis pigmentosa (RP). Studies have found that NAC is generally safe and well-tolerated, and it may support the eye's cone cells, which are crucial for vision. In an earlier trial, people with RP who took NAC for six months showed slight improvements in vision tests. This suggests that NAC might slow the damage to cone cells caused by RP. Since harmful molecules can damage these cells, NAC's ability to reduce this damage could explain its effectiveness. ^{1 2 6 7 8}

Who Is on the Research Team?

Peter A Campochiaro, MD

Principal Investigator

Johns Hopkins University

Xiangrong Kong

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

Adults aged 18-65 with Retinitis Pigmentosa (RP), willing to consent and follow the study protocol, not taking supplements other than vitamin A, and using contraception if of childbearing potential. Excluded are those with uncontrolled blood pressure, recent participation in another drug/device trial, certain genetic disorders like phenylketonuria or fructose intolerance, active cancer within a year (with exceptions), eye conditions that could affect results, severe myopia over -8 diopters, liver disease, cystic fibrosis, asthma/COPD or renal failure.

Inclusion Criteria

Both of my eyes are affected by RP, losing night vision and field of view but still see clearly.

Ability and willingness to provide informed consent

Ability and willingness to comply with the study protocol and to participate in all study visits and assessments in the investigator's judgement

Exclusion Criteria

My blood pressure is not under control.

I have a history of liver disease, cystic fibrosis, asthma, COPD, low platelet count, or other blood disorders.

I am receiving treatment for kidney failure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 1800 mg of N-acetylcysteine or placebo twice a day for 45 months

45 months

Regular visits at 4.5, 9, 18, 27, 36, 40.5, and 45 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• N-acetylcysteine
• Placebo

Trial Overview The clinical trial is testing whether long-term use of N-acetylcysteine (NAC) can slow down cone degeneration in patients with RP by reducing oxidative stress. Participants will either receive NAC or a placebo for several years across multiple locations internationally.

How Is the Trial Designed?

Group I: Group 1 - N-acetylcysteine Experimental Treatment 1 Intervention

This is the intervention group. Patients in this group will be receiving 1800 mg of N-acetylcysteine in the form of 3 effervescent 600 mg tablets dissolved in water twice a day for 45 months.

Group II: Group 2 - Placebo Placebo Group 1 Intervention

Patients in the placebo group will receive identical effervescent tablets lacking active drug.

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

Approved in United States as N-acetylcysteine for:

• Acetaminophen overdose
• Chronic bronchitis
• Cystic fibrosis
• Mucolytic agent

Approved in European Union as N-acetylcysteine for:

• Paracetamol overdose
• Chronic bronchitis
• Cystic fibrosis
• Mucolytic agent

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

McGill University

Collaborator

Trials

421

Recruited

1,017,000+

Medical University of Graz

Collaborator

Trials

524

Recruited

9,334,000+

Radboud University Medical Center

Collaborator

Trials

1,203

Recruited

1,157,000+

Universität Tübingen

Collaborator

Trials

30

Recruited

14,900+

Retina Foundation of the Southwest

Collaborator

Trials

15

Recruited

1,600+

University of Florida

Collaborator

Trials

1,428

Recruited

987,000+

Stanford University

Collaborator

Trials

2,527

Recruited

17,430,000+

Massachusetts Eye and Ear Infirmary

Collaborator

Trials

115

Recruited

15,000+

Northwestern University

Collaborator

Trials

1,674

Recruited

989,000+

Published Research Related to This Trial

In a study involving 30 patients with retinitis pigmentosa, higher doses of N-acetylcysteine (NAC) were linked to a reduced risk of sensitivity loss in the macula, suggesting that NAC may help protect vision during treatment.

The research found that loci with low baseline sensitivity were more likely to show both decreases and increases in sensitivity, with foveal regions showing a greater likelihood of improvement, indicating that areas with higher cone density may respond better to NAC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Locus-Level Changes in Macular Sensitivity in Patients with Retinitis Pigmentosa Treated with Oral N-acetylcysteine. Kong, X., Hafiz, G., Wehling, D., et al.[2022]

In a study involving 8 patients with retinitis pigmentosa, treatment with a topical carbonic anhydrase inhibitor (2% dorzolamide) led to significant reductions in foveal thickness and foveal zone thickness, indicating a positive effect on cystoid macular edema.

Three out of the eight patients experienced clinically significant improvements in visual acuity, suggesting that this treatment may not only reduce edema but also enhance vision in some individuals with retinitis pigmentosa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continued use of dorzolamide for the treatment of cystoid macular oedema in patients with retinitis pigmentosa. Fishman, GA., Apushkin, MA.[2022]

Oral N-acetylcysteine (NAC) is safe and well tolerated in patients with moderately advanced retinitis pigmentosa (RP), with a maximum tolerated dose of 1800 mg twice daily, despite some gastrointestinal side effects that resolved with dose adjustments.

The treatment showed significant improvements in best-corrected visual acuity (BCVA) over 24 weeks, particularly in the higher dose cohort (1800 mg), suggesting NAC may enhance the function of compromised cone photoreceptors in RP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral N-acetylcysteine improves cone function in retinitis pigmentosa patients in phase I trial. Campochiaro, PA., Iftikhar, M., Hafiz, G., et al.[2020]

Gene therapy targeting the RPE65 mutation in Leber congenital amaurosis (LCA) has shown promising results in six patients, leading to significant visual improvements without any reported side effects.

The successful outcomes in these trials suggest potential for further research in younger patients and higher dosages, as well as applications to other related retinal disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful RPE65 gene replacement and improved visual function in humans. Koenekoop, RK.[2012]

In a study involving 79 eyes of 40 patients with chronic posterior blepharitis, N-acetylcysteine (NAC) significantly improved the fluorescein break-up time (FBUT) and mucous fern pattern, indicating enhanced tear stability and eye surface health.

The mechanism of action for NAC in this context is believed to involve the blocking of lipid peroxidation, which may help alleviate symptoms of chronic blepharitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-acetylcysteine in chronic blepharitis. Yalçin, E., Altin, F., Cinhüseyinoglue, F., et al.[2019]

Oral administration of N-acetylcysteine (NAC) significantly reduced cone cell death and preserved cone function in two mouse models of retinitis pigmentosa (RP) for at least 6 months, indicating its potential as a long-term treatment.

Topical application of NAC also effectively reduced oxidative damage in the retina, suggesting that both oral and topical forms of NAC could be safe and feasible options for prolonged treatment in humans with RP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-Acetylcysteine promotes long-term survival of cones in a model of retinitis pigmentosa. Lee, SY., Usui, S., Zafar, AB., et al.[2013]

The first Brazilian patient with RPE65 deficiency was treated with voretigene neparvovec-rzyl (VN), showing no complications and stable best-corrected visual acuity after treatment.

Significant improvements were observed in the patient's full-field stimulus threshold and visual fields, enhancing their ability to perform daily activities, particularly in low-light conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The first gene therapy for RPE65 biallelic dystrophy with voretigene neparvovec-rzyl in Brazil. Ferraz Sallum, JM., Godoy, J., Kondo, A., et al.[2022]

A novel point mutation in the RPE65 gene (c.353G>A, p.(Arg118Lys)) was identified in a 40-year-old male with severe retinitis pigmentosa, which is associated with significant macular atrophy, highlighting its potential role in the disease's pathology.

This mutation, previously classified as likely benign, is suggested to be reclassified as likely pathogenic, indicating that patients with this mutation may be eligible for genetic treatment with voretigene neparvovec, a therapy aimed at providing a functional RPE65 gene.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RPE65 c.353G>A, p.(Arg118Lys): A Novel Point Mutation Associated with Retinitis Pigmentosa and Macular Atrophy Bjeloš, M., Bušić, M., Ćurić, A., et al.[2023]

In a study of 81 subjects with retinitis pigmentosa, 40% of eyes treated with topical dorzolamide showed a significant reduction in cystoid macular edema, with an average decrease in central subfield thickness of 105 μm after about 3 months.

Oral acetazolamide also showed efficacy, with 28.1% of eyes improving in thickness by an average of 115 μm over a median of 4 months, indicating both treatments can be effective for managing CME in retinitis pigmentosa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and prognostic factors of response to carbonic anhydrase inhibitors in management of cystoid macular edema in retinitis pigmentosa. Liew, G., Moore, AT., Webster, AR., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7269599/

Oral N-acetylcysteine improves cone function in retinitis ... Oral NAC is safe and well tolerated in patients with moderately advanced RP and may improve suboptimally functioning macular cones.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05537220

Oral N-acetylcysteine for Retinitis Pigmentosa (NAC Attack) In a phase I clinical trial in patients with RP, NAC taken by month for 6 months caused some small improvements in two different vision tests suggesting that ...

3. fightingblindness.org fightingblindness.org/news/nacuity-s-antioxidative-therapy-naca-performs-encouragingly-in-phase-1-2-clinical-trial-2785

Nacuity's Antioxidative Therapy NACA Performs ... NACA is a gene-agnostic, oral medication designed to preserve vision in people with retinitis pigmentosa and Usher syndrome.

4. nacuity.com nacuity.com/development-programs/

Development Programs The results of this 24-week study of 30 subjects showed that oral NAC was relatively well-tolerated and suggested slight improvements in suboptimally ...

5. hopkinsmedicine.org hopkinsmedicine.org/wilmer/research/nac-attack

NAC Attack Clinical Trial This study observed 1800mg twice per day was tolerable. This supports the next step of a multicenter, randomized, placebo-controlled and masked clinical trial ...

6. usher-syndrome.org usher-syndrome.org/research/clinical-trials.html

Current Clinical Trials & Natural History Studies This Phase 3 study is recruiting and will test whether oral N-acetylcysteine (NAC) is safe and beneficial for patients with RP. NAC is a tablet that was ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S135094622500076X

Keeping the Lights On: a new Role for an old Drug to ... Oral N-acetylcysteine improves cone function in retinitis pigmentosa patients in phase I trial. Journal of Clinical Investigation, 130 (2020) ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03999021

Study Details | NCT03999021 | FIGHT-RP 1 Extension Study Since oral and/or topical administration of NAC is feasible for long-term treatment in humans, and NAC has a good safety profile, there is good rationale to ...