Disulfiram for Retinal Degeneration

Overseen By Evan Burr

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Rochester

Must be taking: Disulfiram

Must not be taking: Anticoagulants, others

Disqualifiers: Cardiovascular disease, Diabetes, Psychosis, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 26 weeks

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether disulfiram can improve vision in individuals with retinal degeneration, a condition affecting the retina that can lead to vision loss. Disulfiram, typically used to manage alcohol use disorder, is being tested for its potential benefits on vision. Participants will receive either the drug or a placebo for 180 days. This trial is suitable for those with retinal dystrophy or dry-AMD who also have alcohol use disorder and are prepared to abstain from alcohol during the study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this treatment for vision issues.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on anticoagulant therapy or other medications that may be affected by disulfiram. It's best to discuss your current medications with the trial team to see if they are compatible.

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

Research has shown that disulfiram, also known as Antabuse, is generally safe for use. The FDA has approved it for treating alcohol use disorder, indicating it has passed safety tests for that purpose. In animal studies, disulfiram showed promise in improving vision in cases of retinal degeneration. While these findings are encouraging, this trial remains in the early stages. Researchers are still learning about its safety and effects on vision in people with retinal problems. Trial participants will be closely monitored to ensure their safety and manage any possible side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for retinal degeneration, which often focus on slowing progression through supplements or injections like anti-VEGF therapies, disulfiram offers a novel approach by repurposing a medication originally used for alcohol dependence. Researchers are excited about disulfiram because it targets a different pathway, potentially reducing oxidative stress linked to retinal damage. This unique mechanism of action could pave the way for a groundbreaking treatment with potentially fewer side effects and a novel method to preserve vision.

What evidence suggests that disulfiram might be an effective treatment for retinal degeneration?

Research has shown that disulfiram, also known as Antabuse®, may improve vision in animals with retinal damage. It reduces certain chemicals that cause overactive signals in the eye, potentially restoring some vision. Studies in mice found that disulfiram can decrease the "sensory noise" that impairs clear vision. This suggests the drug might help people with eye conditions like retinitis pigmentosa and possibly age-related macular degeneration. While these results are promising, this trial will evaluate disulfiram's effectiveness in humans. Participants will receive either the drug or a placebo for 180 days. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for patients with various types of retinal degeneration, such as Stargardt Disease and Age-Related Macular Degeneration. Participants must also be receiving disulfiram for alcohol use disorder management. Specific inclusion and exclusion criteria details are not provided.

Inclusion Criteria

Intact inner nuclear layer, inner plexiform, and ganglion cell layer on macular SD-OCT

Patients must agree to refrain from all alcohol consumption for 180 days

Best Corrected Visual Acuity (BCVA) of 20/20 to Light Perception in the better eye

Exclusion Criteria

A condition that, in the opinion of the investigator, would preclude participation in the study, e.g., cardiovascular disease, hepatitis

Participants who expect to move out of the area of the clinical center during the 8 months of the study

History of psychosis

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either disulfiram or placebo for 180 days to evaluate its impact on visual acuity in patients with retinal degeneration

26 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Disulfiram

Trial Overview

The study is testing the effects of oral disulfiram (Antabuse®) on improving vision in patients with retinal degeneration. It's based on findings that it may reduce hyperactivity in the retina by decreasing Retinoic Acid synthesis.

How Is the Trial Designed?

Group I: All participants Experimental Treatment 1 Intervention

Participants will receive either drug or placebo for 180 days.

Disulfiram is already approved in United States, European Union for the following indications:

Approved in United States as Antabuse for:

• Alcohol dependence

Approved in European Union as Antabuse for:

• Alcohol dependence

Who Is Running the Clinical Trial?

University of Rochester

Lead Sponsor

Trials

883

Recruited

555,000+

Published Research Related to This Trial

Modulators targeting the RPE65 enzyme in the visual cycle can help protect the retina from damage by forming retinaldehyde adducts, but direct inhibition of RPE65 can lead to adverse effects due to slowed visual pigment regeneration.

A new series of compounds, including an isopropyl derivative, showed reduced RPE65 inhibitory activity while still providing some retinal protection, indicating that balancing RPE65 inhibition and retinal sequestration could be key for developing effective treatments for retinal disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rational Tuning of Visual Cycle Modulator Pharmacodynamics. Kiser, PD., Zhang, J., Badiee, M., et al.[2020]

A case study of an ichthyologist revealed that chronic skin exposure to the fish anesthetic MS-222 led to significant visual problems and electroretinogram abnormalities, indicating retinotoxic effects similar to those seen in animal studies.

After stopping exposure to MS-222 for 7 months, the ichthyologist's vision and electroretinogram readings returned to normal, highlighting the potential for recovery after ceasing contact with this harmful substance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retinal toxicity associated with occupational exposure to the fish anesthetic MS-222. Bernstein, PS., Digre, KB., Creel, DJ.[2019]

DMSO (dimethyl sulphoxide) at concentrations of 0.6% or higher causes a significant, dose-dependent decrease in retinal function in Long Evans rats, particularly affecting the mid-retinal bipolar and inner retinal responses, while photoreceptors remain unaffected at all doses.

A single dose of DMSO at or below 0.1% is considered safe for use in the vitreous of rat eyes, as it does not impair retinal function, whereas higher doses lead to short-term retinal dysfunction lasting at least 24 hours.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dimethyl sulphoxide dose-response on rat retinal function. Tsai, TI., Bui, BV., Vingrys, AJ.[2021]

In a study involving 220 patients with dry eye disease, both 1% and 2% rebamipide solutions significantly improved tear film break-up time (TBUT) and tear volume compared to a placebo after 12 weeks of treatment.

The 2% rebamipide solution showed a greater reduction in corneal staining scores than the placebo, indicating its potential effectiveness in stabilizing the ocular surface in patients with dry eye disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of 1% and 2% rebamipide clear solution in dry eye disease: a multicenter randomized trial. Eom, Y., Chung, SH., Chung, TY., et al.[2023]

In a study involving 40 patients with dry eye syndrome after penetrating keratoplasty, both rebamipide (REB) and diquafosol (DQS) significantly improved tear breakup time and corneal staining scores after 4 weeks of treatment.

The improvements in ocular surface health were similar for both treatments, indicating that REB and DQS are equally effective options for managing dry eye syndrome post-surgery, although neither showed significant changes in quality of life scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Comparison Between Rebamipide Ophthalmic Suspension and Diquafosol Ophthalmic Solution for Dry Eye After Penetrating Keratoplasty. Kobashi, H., Kamiya, K., Shimizu, K.[2022]

Medications can cause a wide range of ocular disorders, with the eyelids and conjunctiva being the most frequently affected areas, often due to inflammation or hypersensitivity reactions, particularly from drug preservatives in topical treatments.

Long-term use of glucocorticoids is associated with increased intraocular pressure leading to open-angle glaucoma and the development of cataracts, highlighting the need for careful monitoring of ocular health in patients on these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug-induced ocular disorders. Li, J., Tripathi, RC., Tripathi, BJ.[2021]

Bisphosphonates have been linked to ocular inflammation, including newly reported cases of drug-related scleritis, highlighting a significant safety concern for patients using these medications.

Topiramate has been identified as a cause of angle-closure glaucoma, while cetirizine can lead to oculogyric crises, and retinoids are strongly associated with intracranial hypertension, indicating the need for careful monitoring of these drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse ocular drug reactions recently identified by the National Registry of Drug-Induced Ocular Side Effects. Fraunfelder, FW., Fraunfelder, FT.[2018]

Toxic retinopathies can be caused by external substances like nicotine and methanol, as well as by systemic drugs, making it crucial to differentiate these effects from other retinal diseases.

The paper discusses confirmed and potential side effects of various medications, emphasizing the need for careful screening to recognize these adverse effects, especially for long-approved and novel drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Toxic retinopathies]. Kellner, U., Kellner, S., Weinitz, S., et al.[2020]

There is a significant need for new treatments for dry age-related macular degeneration (AMD), and repurposing existing FDA-approved drugs presents a promising strategy.

Several classes of drugs, including GPR-143 agonists, anti-diabetic medications, mitochondrial activators, and serotonin pathway drugs, are being explored for their potential to reduce AMD diagnosis, highlighting the innovative approach of using existing medications for new therapeutic purposes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repurposing Drugs for Treatment of Age-Related Macular Degeneration. Francisco, SG., Rowan, S.[2023]

Emerging treatments for dry age-related macular degeneration (AMD) focus on two main strategies: preventing cell loss through neuroprotection and oxidative damage prevention, and suppressing inflammation.

Current and potential therapies include neuroprotective drugs, micronutrient supplementation, visual cycle modulators, and anti-inflammatory agents, suggesting a combination approach may be most effective in managing AMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New approaches and potential treatments for dry age-related macular degeneration. Damico, FM., Gasparin, F., Scolari, MR., et al.[2022]

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