Purpose

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, Mexico, and Europe designed to determine if taking NAC for several years provides benefit in patients with RP.

Condition

Eligibility

Eligible Ages
Between 18 Years and 65 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

General - Ability and willingness to provide informed consent - Age ≥ 18 and ≤65 years at time of signing Informed Consent Form - Ability and willingness to comply with the study protocol and to participate in all study visits and assessments in the investigator's judgement - For candidates of childbearing potential: willingness to use a method of contraception - Agreement not to take supplements other than vitamin A Ocular Inclusion Criteria - Both eyes must exhibit the RP phenotype with evidence of loss of night vision, gradual constriction of visual fields, and maintenance of visual acuity; - In addition, an eye must meet the following criteria to be included in the study: - Gradable EZ on a horizontal SD-OCT scan through the fovea center with width ≤ 8000 µm and ≥1500 µm and with well-defined truncation at both the nasal and temporal sides; - BCVA ≥ ETDRS letter score of 61 (20/60 Snellen equivalent); - Sufficiently clear ocular media and adequate pupillary dilation to allow good quality images sufficient for analysis and grading by central reading center.

Exclusion Criteria

General Exclusion Criteria - Active cancer within the past 12 months, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or prostate cancer with Gleason score ≤ 6 and stable prostate specific antigen for > 12 months - Renal failure requiring renal transplant, hemodialysis, peritoneal dialysis, or anticipated to require hemodialysis or peritoneal dialysis during the study - Liver disease, cystic fibrosis, asthma, or chronic obstructive pulmonary disease (COPD), history of thrombocytopenia not due to a reversible cause or other blood dyscrasia - Uncontrolled blood pressure (defined as systolic > 180 and/or diastolic > 100 mmHg while at rest) at screening. If a patient's initial measurement exceeds these values, a second reading may be taken 30 or more minutes later. If the patient's blood pressure must be controlled by antihypertensive medication, the patient may become eligible if medication is taken continuously for at least 30 days. - History of other disease, physical examination finding, or clinical laboratory finding giving reasonable suspicion that oral NAC may be contraindicated or that follow up may be jeopardized - Cerebrovascular accident or myocardial infarction within 6 months of screening - Participation in an investigational study that involves treatment with any drug or device within 6 months of screening - Three relatives already enrolled in study - Pregnant, breast feeding, or intending to become pregnant during the study treatment period. Women of childbearing potential who have not had tubal ligation must have a urine pregnancy test at screening. - Known history of allergy to NAC - Having taken NAC in any form in the past 4 months - Phenylketonuria - Fructose intolerance - Glucose-galactose malabsorption - Sucrase-isomaltase insufficiency - Abnormal laboratory value including the value of alanine aminotransferase (ALT), aspartate aminotransferase (AST), or bilirubin being greater than 1.5 x the upper limit of normal - Any major abnormal findings on blood chemistry, hematology, and renal function lab tests that in the opinion of the Site Investigator and/or the Study Chair makes the candidate not suitable to participate in the trial - HIV or hepatitis B infection Ocular Exclusion Criteria - Evidence of cone-rod dystrophy or pattern dystrophy including focal areas of atrophy or pigmentary changes in the central macula - Cystoid spaces involving the fovea substantially reducing vision - Glaucoma or other optic nerve disease causing visual field loss or reduced visual acuity - Intra ocular pressure >27 mm Hg from two measurements. If a patient's initial measurement exceeds 27 mm Hg, a second reading must be taken. - Any retinal disease other than RP causing reduction in visual field or visual acuity - Any prior macular laser photocoagulation - Intraocular surgery within 3 months prior to screening - High myopia with spherical equivalent refractive error > 8 diopters. If an eye has had cataract surgery or refractive surgery, a pre-operative refractive error spherical equivalent > 8 diopters is an exclusion - Any concurrent ocular condition that might affect interpretation of results - History of uveitis in either eye

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
438 participants will be enrolled and randomized at approximately 30 clinical sites in the Americas and Europe. Patients will be eligible if both eyes have an RP phenotype consisting of severe loss of rod function (night blindness) followed by progressive constriction of visual fields with best-corrected visual acuity (BCVA) of 20/60 or better. Gradable ellipsoid zone (EZ) width on the horizontal fovea spectral domain-optical coherence tomography (SD-OCT) scan must be < 8000 µm and ≥ 1500 µm. Eligible patients will be randomized 2:1 to NAC 1800 mg bid versus placebo. The primary efficacy objective is to determine if the progressive loss in EZ width measured as the cumulative loss of EZ (calculated as the area above the curve) between baseline and month (M) 45 is significantly less in eyes of participants taking NAC 1800 mg bid compared with that in eyes of participants taking placebo. The safety objective is to evaluate the long-term safety and tolerability of oral NAC for 45 months.
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Group 1 - N-acetylcysteine
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.
  • Drug: N-acetylcysteine
    After randomization, participants will be given about 10-months supply of study drug (intervention), with instructions to take 3 effervescent tablets in water twice a day. They will return to the clinic at M4.5 for evaluation and then at M9, M18, M27, M36, M40.5 and M45. At each in-clinic visit, drug reconciliation will occur. At each visit at Baseline, M9, M18, M27, M36, that is, every 9 months, participants will be given another 10-month supply of study drug.
Placebo Comparator
Group 2 - Placebo
Patients in the placebo group will receive identical effervescent tablets lacking active drug.
  • Drug: Placebo
    After randomization, participants will be given about 10-months supply of placebo, with instructions to take 3 effervescent tablets in water twice a day. They will return to the clinic at M4.5 for evaluation and then at M9, M18, M27, M36, M40.5 and M45. At each in-clinic visit, efficacy and safety assessments will be done and drug reconciliation will occur. At baseline, M9, M18, M27, and M36 participants will be given another 10-month supply of placebo.

Recruiting Locations

University of California - Davis, Department of Ophthalmology & Vision Science
Davis, California 95817
Contact:
Denise Macias, CCRP
916-734-6303
dcmacias@ucdavis.edu

University of Southern California, Keck School of Medicine
Los Angeles, California 90089
Contact:
Mariana Edwards Mariana Edwards
323-442-6490
Mariana.Edwards@med.usc.edu

University of California - San Francisco, Department of Ophthalmology
San Francisco, California 94158
Contact:
Nicholas Bobbitt
Nicholas.Bobbitt@ucsf.edu

Stanford University, Byers Eye Institute
Stanford, California 94303
Contact:
Lorraine Almeada
650-497-9205
lalmeda@stanford.edu

Vitreo Retinal Associates
Gainesville, Florida 32607
Contact:
Jing Zhang
352-300-8412
jingzhang@vra-pa.com

University of Florida - Jacksonville, UF Health Jacksonville
Jacksonville, Florida 32209
Contact:
Ghulam S Hamdani
904-244-9305
Ghulam.hamdani@jax.ufl.edu

University of Miami, Bascom Palmer Eye Institute
Miami, Florida 33136
Contact:
Adriana Padilla Drada
apd86@med.miami.edu

Emory University, Emory Eye Center
Atlanta, Georgia 30322
Contact:
Lindy DuBois, MEd, MMS
404-778-4443
ldubois@emory.edu

University Of Illinois At Chicago
Chicago, Illinois 60612
Contact:
Jianrong (Sharon) Sheng
312-996-1783
jiashe@uic.edu

Northwestern University
Evanston, Illinois 60208
Contact:
Davis Bhagat
davis.bhagat@northwestern.edu

University of Iowa, Carver College of Medicine
Iowa City, Iowa 52242
Contact:
Arlene V Drack, MD
arlene-drack@uiowa.edu

Wilmer Eye Institute- Johns Hopkins University
Baltimore, Maryland 21287
Contact:
Dagmar Wehling
410-502-7621
dwehlin1@jhu.edu

Harvard University, Mass. Eye and Ear
Boston, Massachusetts 02114
Contact:
Mirjana Nordmann, PhD
617-573-6060
CenterforClinicalResearchOperations@MEEI.HARVARD.EDU

University of Michigan, Kellogg Eye Center
Ann Arbor, Michigan 48105
Contact:
Courtney Soto
734-936-9798
cosoto@med.umich.edu

University of Minnesota, Department of Ophthalmology and Visual Neurosciences
Minneapolis, Minnesota 55455
Contact:
Meaghyn Kramer
612-625-4400
krame706@umn.edu

Mayo Clinic, Department of Ophthalmology
Rochester, Minnesota 55905
Contact:
Suzy Wernimont
Wernimont.Suzanne@mayo.edu

University of Oklahoma, Dean McGee Eye Institute
Oklahoma City, Oklahoma 73104
Contact:
Crystal McAfee
405-271-6307
Crystal-McAfee@dmei.org

Scheie Eye Institute
Philadelphia, Pennsylvania 19104
Contact:
Alexandra Garafalo
215-662-9981

Vanderbilt University, Vanderbilt Eye Institute
Nashville, Tennessee 37211
Contact:
Lindsay Veach
615-421-8216
Lindsay.Veach@vumc.org

Retina Foundation of the Southwest
Dallas, Texas 75231
Contact:
Kaylie Jones
214-363-3911
kwebb@retinafoundation.org;

University of Utah, Moran Eye Center
Salt Lake City, Utah 84132
Contact:
Deborah Harrison
801-585-6645
deborah.harrison@hsc.utah.edu

University of Washington, Department of Ophthalmology
Seattle, Washington 98109
Contact:
Ankanksha Singh
akan06@uw.edu

University of Wisconsin - Madison, McPherson Eye Research Institute
Madison, Wisconsin 53705
Contact:
Nickie J Stangel
608-263-8783
nstangel@wisc.edu

Medical College of Wisconsin, The Eye Institute
Milwaukee, Wisconsin 53226
Contact:
Katie McKenney
414-955-7866
kmckenney@mcw.edu

More Details

NCT ID
NCT05537220
Status
Recruiting
Sponsor
Johns Hopkins University

Study Contact

Xiangrong Kong, PhD
410-502-7621
NACAttackCC@live.johnshopkins.edu

Detailed Description

Retinitis Pigmentosa (RP) is a disease in which one of several different mutations differentially causes degeneration of rod photoreceptors while sparing cone photoreceptors. The loss of rod photoreceptors results in poor vision in dim illumination (night blindness), but does not affect most activities of daily life including reading or driving. However, after most rod photoreceptors are eliminated, cone photoreceptors begin to die, resulting in gradual constriction of visual fields which over time causes visual disability. Rods outnumber cones by a ratio of 95:5 and therefore after mutation-induced degeneration of rods, the majority of cells in the outer retina have been eliminated, markedly reducing oxygen utilization. However, oxygen supply is unchanged resulting in a large excess of tissue oxygen surrounding cones. This results in progressive oxidative damage that contributes to slowly progressive degeneration of cone photoreceptors. N-acetylcysteine (NAC) is a strong antioxidant that is approved for acetaminophen overdose. Orally administered NAC in a mouse model of RP reduced oxidative damage to cones and promoted maintenance of function and survival of cones. In a phase I clinical trial in patients with RP, oral administration of NAC for 6 months was well-tolerated and resulted in a small but statistically significant improvement in visual acuity and light sensitivity in the retina. This suggests that long-term administration of NAC may promote survival and maintenance of function of cones. NAC Attack is a phase III, multicenter, randomized, placebo controlled trial that will determine if oral NAC provides benefit and is safe in patients with RP.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.