Disulfiram (Antabuse) for vision in retinal degeneration

The Effects of Disulfiram on Visual Acuity in Patients With Retinal Degeneration

This study will test whether taking oral disulfiram (Antabuse) improves vision in adults with retinal degeneration who are also being treated for alcohol use disorder.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Rochester (Academic / other)
• Locations: 1 site (Rochester, New York)
• Trial ID: NCT06319872 on ClinicalTrials.gov

What this trial studies

This Phase 1 interventional study gives oral disulfiram to adults with inherited retinal dystrophies or dry age-related macular degeneration who are also candidates for disulfiram treatment of alcohol use disorder. Participants will take disulfiram and undergo serial vision testing and retinal imaging (including best-corrected visual acuity, visual fields, and macular SD-OCT) to look for changes in image-forming vision and inner retinal structure. Key eligibility includes intact inner nuclear, inner plexiform, and ganglion cell layers on macular SD-OCT and a documented diagnosis of alcohol use disorder from an addiction specialist, with agreement to abstain from alcohol for 180 days. The study is conducted at the Flaum Eye Institute, University of Rochester Medical Center and is intended to detect early signals of visual benefit and safety in humans.

Who should consider this trial

Good fit: Adults (18+) with inherited retinal dystrophy or dry AMD who have alcohol use disorder, are candidates for disulfiram treatment, have intact inner retinal layers on macular SD-OCT, and can abstain from alcohol for 180 days.

Not a fit: Patients without alcohol use disorder, those unable to stop drinking, or those with severely damaged inner retinal layers are unlikely to benefit from this treatment.

Why it matters

Potential benefit: If successful, disulfiram could improve or slow loss of image-forming vision in some patients with retinal degeneration.

How similar studies have performed: Preclinical animal studies showed improved image-forming vision after disulfiram via reduced retinoic acid synthesis, but clinical human data are currently limited.

Eligibility criteria

Inclusion Criteria:

* All sexes, 18 years and older.
* Participants must speak English, understand, and sign the informed consent document.
* Stated willingness to comply with all study procedures and availability for the duration of the study.
* In good general health as evidenced by medical history and with a clinical diagnosis of inherited retinal dystrophy or dry-AMD.
* Best Corrected Visual Acuity (BCVA) of 20/20 (with constriction or other defects of Goldmann visual field) to Light Perception in the better eye.
* Intact inner nuclear layer, inner plexiform, and ganglion cell layer on macular SD-OCT.
* Ability to take oral medication and be willing to adhere to the disulfiram regimen.
* Patients must have the diagnosis of alcohol use disorder provided by an addiction specialist and be a candidate for therapeutic use of disulfiram for that condition.
* Patients must agree to refrain from all alcohol consumption for 180 days.
* Any female participant of childbearing potential must have a negative urine pregnancy test at screening.
* Any female participant of childbearing potential must have (or have a partner who has) had a surgical sterilization (vasectomy, hysterectomy, or tubal ligation), be completely abstinent from intercourse or must agree to practice two acceptable methods of contraception throughout the course of the study and for at least one week after disulfiram discontinuation. Acceptable methods of contraception include hormonal contraception (i.e., birth control pills, injected hormones, dermal patch, or vaginal ring); intrauterine device; barrier methods (diaphragm, condom) with spermicide.

Exclusion Criteria:

* A condition that, in the opinion of the investigator, would preclude participation in the study, e.g., cardiovascular disease, hepatitis.
* Individuals with a history of diabetes mellitus.
* Individuals with a history of psychosis.
* Individuals with hypothyroidism.
* Individuals with hypersensitivity to thiuram derivatives causing rubber contact dermatitis.
* Those on anticoagulant therapy or other medications that may be affected by disulfiram.
* Ophthalmic conditions with independent effect upon visual function (e.g. diabetic retinopathy, glaucoma, cataract, vitreous hemorrhage, retinal detachment, active intraocular inflammation or active infectious ocular diseases, choroidal neovascularization).
* Patients with No Light Perception (NLP) in both eyes.
* History of major ocular surgery within the prior 6 months or major ocular surgery anticipated within the next 6 months following randomization.
* Exam evidence of severe external ocular infection, including conjunctivitis, chalazion, or substantial blepharitis
* Participation in an investigational trial that involves treatment with any drug within 30 days of randomization that has not received regulatory approval at the time of study entry. Note: study participants cannot receive another investigational drug while participating in this study.
* Known allergy or hypersensitivity to any component of the study drug.
* For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 12 months.
* Participants who expect to move out of the area of the clinical center during the 8 months of the study

Where this trial is running

Rochester, New York

• Flaum Eye Institute, University of Rochester Medical Center — Rochester, New York, United States (Recruiting)

Study contacts

• Study coordinator: Evan Burr

Conditions Alcohol Use Disorder; Retinal Dystrophies; Age-Related Macular Degeneration; Retinitis Pigmentosa; Stargardt Disease