NCT05537220: NAC Attack

NAC Attack, A Phase III, Multicenter, Randomized, Parallel, Double Masked, Placebo-Controlled Study Evaluating the Efficacy and Safety of Oral N-Acetylcysteine in Patients With Retinitis Pigmentosa

Active, enrolled Phase 3 Last updated 1 May 2026

What this trial tests

Phase 3 trial testing N-acetylcysteine in Retinitis Pigmentosa in 485 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

11 October 2023

Primary endpoint
1 May 2029

1 May 2030

Quick facts

Lead sponsor	Johns Hopkins University
Phase	Phase 3
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	485
Start date	11 October 2023
Primary completion	1 May 2029
Estimated completion	1 May 2030
Sites	31 locations across United States, Austria, Canada, Germany, Netherlands, Switzerland, United Kingdom

Drugs / interventions tested

• N-acetylcysteine — full drug profile →
• Placebo

Conditions studied

• Retinitis Pigmentosa — all drugs for Retinitis Pigmentosa →

Sponsor

Johns Hopkins University

Who can join

Adults 18 to 65, any sex, with Retinitis Pigmentosa. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Progressive change of ellipsoid zone (EZ) width
  Time frame: Baseline and 45 months
  The EZ is a hyperreflective band seen on SD-OCT scans that corresponds to photoreceptors with intact inner and outer segments. In RP patients at the stage of those participating in this trial, the EZ consists primarily of remaining cones with intact inner and outer segments. The EZ width is the length of the EZ on a horizontal SD-OCT scan through the fovea and provides a quantitative measure of su

Sponsor's own description

Retinitis pigmentosa (RP) is an inherited retinal degeneration caused by one of several mistakes in the genetic code. Such mistakes are called mutations. The mutations cause degeneration of rod photoreceptors which are responsible for vision in dim illumination resulting in night blindness. After rod photoreceptors are eliminated, gradual degeneration of cone photoreceptors occurs resulting in gradual constriction of side vision that eventually causes tunnel vision. Oxidative stress contributes to cone degeneration. N-acetylcysteine (NAC) reduces oxidative stress and in animal models of RP it slowed cone degeneration. 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 long-term administration of NAC might slow cone degeneration in RP. NAC Attack is a clinical trial being conducted at many institutions in the US, Canada, and Europe designed to determine if taking NAC for several years provides benefit in patients with RP.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Molecular mechanisms underlying inherited photoreceptor degeneration as targets for therapeutic intervention.
   Bighinati A, Adani E, Stanzani A, D'Alessandro S, et al · · 2024 · cited 26× · PMID 38370034 · DOI 10.3389/fncel.2024.1343544
2. Gene-agnostic approaches to treating inherited retinal degenerations.
   Chew LA, Iannaccone A. · · 2023 · cited 14× · PMID 37123404 · DOI 10.3389/fcell.2023.1177838
3. Recent advances in the understanding of cilia mechanisms and their applications as therapeutic targets.
   Saito M, Otsu W, Miyadera K, Nishimura Y. · · 2023 · cited 10× · PMID 37780208 · DOI 10.3389/fmolb.2023.1232188
4. Inherited Retinal Degenerations and Non-Neovascular Age-Related Macular Degeneration: Progress and Unmet Needs.
   Duncan JL, Bowman A, Laster A, Gelfman C, et al · · 2024 · cited 5× · PMID 39688851 · DOI 10.1167/tvst.13.12.28
5. RHO-Associated Retinitis Pigmentosa: Genetics, Phenotype, Natural History, Functional Assays, and Animal Model - In Preparation for Clinical Trials.
   Daich Varela M, Romo-Aguas JC, Guarascio R, Ziaka K, et al · · 2025 · cited 3× · PMID 40736177 · DOI 10.1167/iovs.66.9.69
6. Longitudinal Changes in Optoretinography Provide an Early and Sensitive Biomarker of Outer Retinal Disease.
   Liu T, Wendel BJ, Huey J, Pandiyan VP, et al · · 2025 · cited 3× · PMID 40447249 · DOI 10.1016/j.ajo.2025.05.032
7. Oxidative Stress, Inflammation and Altered Glucose Metabolism Contribute to the Retinal Phenotype in the Choroideremia Zebrafish.
   Méjécase C, Nair N, Sarkar H, Soro-Barrio P, et al · · 2024 · cited 2× · PMID 39765914 · DOI 10.3390/antiox13121587
8. Current approaches for Usher syndrome disease models and developing therapies.
   Leith FK, Lye J, Delaney DS, McLenachan S, et al · · 2025 · cited 1× · PMID 40620763 · DOI 10.3389/fcell.2025.1547523