N-acetylcysteine for Retinitis Pigmentosa

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Johns Hopkins University

Must be taking: N-acetylcysteine

Disqualifiers: Age-related macular degeneration, diabetic retinopathy, retinal vein occlusion, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether N-acetylcysteine (NAC), a potent antioxidant, can slow or stop vision loss in individuals with Retinitis Pigmentosa (RP), a serious eye condition that leads to tunnel vision and eventually blindness. Researchers believe NAC could protect the eye's cone cells from oxidative damage, a key factor in RP. Participants will take NAC in effervescent tablet form. Suitable candidates for this trial are those diagnosed with RP who do not have other eye diseases like macular degeneration or diabetic retinopathy. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this potentially groundbreaking therapy.

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

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that N-acetylcysteine (NAC) is generally safe. Many studies have tested this antioxidant for conditions like cystic fibrosis and chronic obstructive pulmonary disease (COPD), using doses up to 1800 mg per day, which have been well-tolerated. The most common side effects include stomach issues like nausea and diarrhea, though these are rare.

One study found that participants took a high dose of 11.2 grams per day for three months without serious problems. However, some less common reactions include allergies, breathing problems, and skin rashes. For retinitis pigmentosa (RP), a type of eye disease, NAC has been tested on patients without major issues. Specifically, the FIGHT-RP 1 Study found that doses up to 1800 mg twice a day were safe.

Overall, NAC has a strong safety record, and many people tolerate it well. ^{1 2 3 4 5}

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

Most treatments for Retinitis Pigmentosa focus on managing symptoms and slowing progression using vitamin A supplements, DHA, and sometimes gene therapy. However, N-acetylcysteine (NAC) is unique because it targets oxidative stress, which is a significant factor in the degeneration of retinal cells in this condition. NAC works as an antioxidant, potentially offering a new way to protect retinal cells from damage. Researchers are excited about NAC because it could offer a more direct approach to preserving vision by addressing one of the underlying causes of cell damage rather than just managing symptoms.

What evidence suggests that NAC might be an effective treatment for Retinitis Pigmentosa?

Research shows that N-acetylcysteine (NAC) might help treat retinitis pigmentosa (RP), a condition affecting vision. Earlier studies found that NAC improved the function of macular cones, which are crucial for central vision, in people with moderately advanced RP. Animal studies suggest that NAC, a strong antioxidant, protects the eye's cone cells from damage. In one study, a similar compound reduced the loss of light-sensitive cells by over 50% in Usher syndrome, a condition related to RP. While these findings are promising, more research is needed to confirm NAC's effectiveness in people with RP. In this trial, all participants will receive NAC effervescent tablets to further evaluate its potential benefits for RP. ^{1 3 4 6 7}

Who Is on the Research Team?

Peter Campochiaro

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Retinitis Pigmentosa (RP), a condition leading to vision loss. Participants must consent to use their health information and understand the study's details. It excludes those with other eye diseases affecting central vision, active eye infections, or uncontrolled high blood pressure.

Inclusion Criteria

I have been diagnosed with retinitis pigmentosa.

Authorization of use and disclosure of protected health information

Informed consent

Exclusion Criteria

I have an eye condition affecting the center of my vision.

My blood pressure is not controlled even with medication.

I currently have an eye infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive N-Acetylcysteine (NAC) at a dose of 1800 mg twice a day

Up to 2 years

Visits every three months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants may continue receiving NAC to assess long-term safety and tolerability

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• NAC effervescent tablets

Trial Overview The FIGHT-RP 1 Extension Study tests NAC effervescent tablets as a potential treatment for RP. The study builds on previous findings that suggest antioxidants like NAC could help preserve eyesight in RP by reducing oxidative damage in the retina.

How Is the Trial Designed?

Group I: Experimental Arm Experimental Treatment 1 Intervention

All participants to receive study intervention.

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Zambon SpA

Industry Sponsor

Trials

31

Recruited

6,300+

Published Research Related to This Trial

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]

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]

N-acetylcysteine (NAC) is an antioxidant that helps replenish glutathione and has various mechanisms of action, making it useful in both prescription and over-the-counter applications.

Despite its long history and potential benefits in treating rare diseases related to mitochondrial dysfunction, there is a lack of comprehensive clinical studies on NAC's pharmacokinetics and pharmacodynamics, highlighting the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-acetylcysteine Pharmacology and Applications in Rare Diseases-Repurposing an Old Antioxidant. Sahasrabudhe, SA., Terluk, MR., Kartha, RV.[2023]

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]

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]

N-acetylcysteine (NAC) effectively increases plasma cysteine and glutathione levels, particularly at a dose of 70 mg/kg, which also correlates with improved handgrip exercise performance.

Higher doses of NAC (140 mg/kg) can lead to significant gastrointestinal adverse reactions, suggesting that lower doses may be safer and still effective for enhancing thiol levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-acetylcysteine in handgrip exercise: plasma thiols and adverse reactions. Ferreira, LF., Campbell, KS., Reid, MB.[2021]

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]

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. 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 ...

3. nacuity.com nacuity.com/?page_id=624

Nacuity Pharmaceuticals Announces Positive Data from ... NPI-001 shows more than 50% reduction in photoreceptor loss caused by RP associated with USH over two years. NPI-001 was well tolerated, ...

4. 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.

5. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT05537220

Oral N-acetylcysteine for Retinitis Pigmentosa 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 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31805012/

Oral N-acetylcysteine improves cone function in retinitis ... N-acetylcysteine (NAC) reduces oxidative damage and increases cone function/survival in RP models. We tested the safety, tolerability, and ...

7. clinicaltrial.be clinicaltrial.be/en/details/5130?per_page=20&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

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 ...