N-acetylcysteine for Retinitis Pigmentosa

(NAC Attack Trial)

Recruiting at34 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Johns Hopkins University

Disqualifiers: Active cancer, Renal failure, Liver disease, others

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing if N-acetylcysteine (NAC) can help slow down vision loss in people with Retinitis Pigmentosa (RP). RP is a genetic condition that causes gradual vision loss. NAC reduces damage caused by too much oxygen around eye cells, potentially protecting vision. N-acetylcysteine (NAC) has been shown to reduce oxidative damage and increase cone function/survival in studies related to 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.

What data supports the effectiveness of the drug N-acetylcysteine for retinitis pigmentosa?

Research shows that N-acetylcysteine (NAC) can improve vision and protect eye cells in people with retinitis pigmentosa by reducing oxidative stress (damage caused by harmful molecules). In a study, patients taking NAC experienced improved visual function, and animal studies showed that NAC helped preserve eye cell structure and function over time. ^{1 2 3 4 5}

How does the drug N-acetylcysteine differ from other treatments for retinitis pigmentosa?

N-acetylcysteine (NAC) is unique for retinitis pigmentosa as it is an antioxidant that may help protect retinal cells from oxidative stress, unlike other treatments like gene therapy or carbonic anhydrase inhibitors, which target specific genetic mutations or reduce fluid buildup in the eye. ^{2 6 7 8 9}

Research Team

Peter A Campochiaro, MD

Principal Investigator

Johns Hopkins University

Xiangrong Kong

Principal Investigator

Johns Hopkins University

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• N-acetylcysteine (Antioxidant)
• Placebo (Other)

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.

Participant Groups

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.

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Theodore DeWeese

Johns Hopkins University

Chief Executive Officer since 2023

MD from an unspecified institution

Allen Kachalia

Johns Hopkins University

Chief Medical Officer since 2023

MD from an unspecified institution

McGill University

Collaborator

Trials

421

Recruited

1,017,000+

Philippe Drouet

McGill University

Chief Executive Officer since 2021

Master of Science and Bachelor in Chemical Engineering from McGill University

Marianne Mancini

McGill University

Chief Medical Officer

BS in Nutritional Sciences from McGill University

Medical University of Graz

Collaborator

Trials

524

Recruited

9,334,000+

Prof. Josef Smolle

Medical University of Graz

Chief Executive Officer since 2019

MD from Karl-Franzens University of Graz

Prof. Hildegard T. Greinix

Medical University of Graz

Chief Medical Officer since 2016

MD from Karl-Franzens University of Graz

Radboud University Medical Center

Collaborator

Trials

1,203

Recruited

1,157,000+

Jacques Lemmens

Radboud University Medical Center

Chief Executive Officer since 2020

PhD in Organic Chemistry, University of Nijmegen

Louis Denis

Radboud University Medical Center

Chief Medical Officer

MD, Vrije Universiteit Brussel

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+

Dr. Stephen J. Motew

University of Florida

Chief Executive Officer since 2024

MD cum laude from the University of Illinois at Chicago School of Medicine, Master's in Healthcare Administration from the University of North Carolina at Chapel Hill

Dr. Timothy E. Morey

University of Florida

Chief Medical Officer since 2023

MD and Bachelor's from the University of Florida

Stanford University

Collaborator

Trials

2,527

Recruited

17,430,000+

Dr. Richard A. Miller

Stanford University

Chief Executive Officer since 2023

Stanford University, MD

Dr. Robert Schott

Stanford University

Chief Medical Officer since 2021

University of Michigan, MD

Massachusetts Eye and Ear Infirmary

Collaborator

Trials

115

Recruited

15,000+

CarolAnn Williams

Massachusetts Eye and Ear Infirmary

Chief Executive Officer

MBA from Harvard Business School

Aalok Agarwala

Massachusetts Eye and Ear Infirmary

Chief Medical Officer since 2019

MD from University of California, Los Angeles

Northwestern University

Collaborator

Trials

1,674

Recruited

989,000+

Dr. Jeffrey Sherman

Northwestern University

Chief Medical Officer

MD from Northwestern University

Dr. Alicia Löffler

Northwestern University

Chief Executive Officer since 2010

PhD from the University of Massachusetts at Amherst, post-doctoral training at Caltech

Findings from Research

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]

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 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]

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]

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]

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]

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]

References

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

Locus-Level Changes in Macular Sensitivity in Patients with Retinitis Pigmentosa Treated with Oral N-acetylcysteine. [2022]

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

Continued use of dorzolamide for the treatment of cystoid macular oedema in patients with retinitis pigmentosa. [2022]

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

N-acetylcysteine in chronic blepharitis. [2019]

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

Oral N-acetylcysteine improves cone function in retinitis pigmentosa patients in phase I trial. [2020]

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

N-Acetylcysteine promotes long-term survival of cones in a model of retinitis pigmentosa. [2013]

6. England pubmed.ncbi.nlm.nih.gov

The first gene therapy for RPE65 biallelic dystrophy with voretigene neparvovec-rzyl in Brazil. [2022]

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

Efficacy and prognostic factors of response to carbonic anhydrase inhibitors in management of cystoid macular edema in retinitis pigmentosa. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

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

9. England pubmed.ncbi.nlm.nih.gov

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