Disulfiram for Retinal Degeneration

Overseen By Debarshi Mustafi, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Washington

Must not be taking: Anticoagulants, others

Disqualifiers: Diabetes, Psychosis, Hypothyroidism, others

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether disulfiram, a medication approved for other uses, can improve vision in people with inherited retinal degeneration, a condition where vision deteriorates over time. The trial compares disulfiram to a placebo (a harmless, inactive substance) to determine if it can prevent or slow vision loss by targeting specific chemical signals in the eye. Individuals diagnosed with inherited retinal degeneration, who can see at least 20/40 with glasses or contacts, and have a specific type of visual field constriction might be suitable candidates. Participants must avoid alcohol during the study and have normal liver function. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking vision research.

Will I have to stop taking my current medications?

The trial does not specify if you must 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 study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that disulfiram, also known as Antabuse®, is already FDA-approved for other uses, suggesting it might be safe for people. This drug, traditionally used to treat alcohol dependence, is now under study to determine if it can improve vision in individuals with retinal degeneration. In animal studies, disulfiram showed promise in enhancing vision by reducing the activity of certain eye cells that can worsen vision loss.

Since disulfiram is in the early stages of clinical trials for this new use, its safety for treating retinal degeneration is still under evaluation. However, its existing approval for other conditions provides some reassurance about its safety in humans. Participants should be aware that this is an experimental use, and the full range of possible side effects is not yet fully known. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Disulfiram is unique because it offers a fresh approach to treating retinal degeneration. Most treatments for this condition, like anti-VEGF injections, primarily focus on slowing disease progression. However, Disulfiram stands out with its potential to repurpose a well-known medication typically used for alcohol dependency, targeting oxidative stress pathways thought to contribute to retinal cell damage. Researchers are excited about its potential to not only halt but possibly reverse some of the damage caused by retinal degeneration, offering hope for improved vision outcomes.

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

This trial will compare the effects of Disulfiram with a placebo in treating retinal degeneration. Studies have shown that Disulfiram, originally used to treat alcohol abuse, may improve vision in people with certain eye diseases. In animal studies, Disulfiram improved vision by reducing unusual activity in the retina, the part of the eye that senses light. Specifically, research found that nearly blind mice treated with Disulfiram were better at seeing images, suggesting it might also help humans. The drug blocks a specific enzyme, which could help stop further vision loss in conditions like retinitis pigmentosa, an inherited eye disease. Early findings also suggest that Disulfiram might help with other eye conditions, such as age-related macular degeneration. ^{2 5 6 7 8}

Who Is on the Research Team?

Debarshi Mustafi, MD, PhD

Principal Investigator

University of Washington

Are You a Good Fit for This Trial?

Adults over 18 with a clinical diagnosis of inherited retinal degeneration, who have relatively good vision (20/40 or better) and can see within 10 degrees centrally. Participants must not drink alcohol for the duration of the study plus two weeks before and after. They should also have normal levels of albumin, total protein, ALT, AST, and ALP.

Inclusion Criteria

You have a narrow field of vision of 10 degrees in the center.

Your AST blood test result is below 40 IU/L.

I am 18 or older with a diagnosed inherited eye condition, possibly supported by genetic testing.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive disulfiram or placebo to evaluate effects on retinal sensitivity and visual function

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Disulfiram
• Placebo

Trial Overview

The trial is testing Disulfiram (250 mg), an FDA-approved drug that may improve visual function by inhibiting a pathway linked to vision loss in retinal degeneration. It's compared against a placebo to evaluate its effectiveness in humans.

How Is the Trial Designed?

Group I: Disulfiram Active Control 1 Intervention

Disulfiram medication

Group II: Placebo Placebo Group 1 Intervention

Placebo medication

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 Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Published Research Related to This Trial

Disulfiram, a drug traditionally used to treat alcoholism, has shown promising anticancer activity, particularly in suppressing liver metastases from ocular melanoma, making it a potential new treatment option.

This drug is not only inexpensive and widely available, but it also has a favorable safety profile compared to conventional cancer treatments, with negligible adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The value of proteasome inhibition in cancer. Can the old drug, disulfiram, have a bright new future as a novel proteasome inhibitor? Cvek, B., Dvorak, Z.[2015]

Disulfiram (Antabuse) effectively inhibits the RNA-dependent DNA polymerase of Rous sarcoma virus, preventing it from causing malignant transformation in chick embryo cells, highlighting its potential anti-cancer properties.

Disulfiram induces the synthesis of specific proteins in normal cells and shows a greater impact on DNA synthesis compared to RNA and protein synthesis, suggesting it may influence cellular processes beyond its use in treating alcoholism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of antabuse (disulfiram) on Rous sarcoma virus and on eukaryotic cells. Levinson, W., Mikelens, P., Oppermann, H., et al.[2019]

In a double-blind trial involving 15 HIV-positive men, disulfiram was administered at doses of 100 mg or 400 mg daily for 4 weeks, but it did not show any significant effects on immune function or overall health.

Despite its potential as an immunomodulating agent, disulfiram did not improve immunological, hematological, or clinical outcomes in participants with low CD4 counts or impaired lymphocyte response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of immunomodulating effect of disulfiram on HIV positive patients. Hørding, M., Gøtzsche, PC., Bygbjerg, IC., et al.[2019]

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]

In a study of 10 patients with chronic graft-versus-host disease (cGVHD), long-term use of 3% diquafosol ophthalmic solution significantly improved symptoms of dry eye disease, particularly corneal and conjunctival health, without major adverse events.

After an average treatment duration of 12 months, diquafosol improved tear film stability and reduced staining scores, indicating its efficacy in managing dry eye symptoms associated with cGVHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Topical Diquafosol Tetrasodium Treatment of Dry Eye Disease Caused by Chronic Graft-Versus-Host Disease: A Retrospective Study. Yamane, M., Ogawa, Y., Fukui, M., et al.[2018]

Disulfiram (Antabuse) is an effective part of alcoholism treatment when combined with counseling and support, and its effectiveness is enhanced by supervised administration to ensure patient compliance.

The disulfiram-ethanol reaction (DER) is crucial for demonstrating the drug's effectiveness, serving as a positive reinforcement for sobriety, and the therapy is generally safe with few serious side effects, although there are specific concerns regarding hepatotoxicity, especially in women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How to get the best out of antabuse. Kristenson, H.[2013]

In a study of 97 patients with inactive tuberculous chorioretinitis, retinalamine injections significantly improved retinal function, leading to a 66.3% increase in visual acuity and enhanced electrophysiological activity in the majority of cases.

Retinalamine treatment also slowed the progression of age-related cataracts, preventing vision loss in a high percentage of patients over four years, demonstrating its potential as an effective bioregulator in ocular tuberculosis management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment with the peptide bioregulator retinalamine in patients with tuberculosis of the organ of vision]. Aleksandrov, EI., Aleksandrova, TE.[2008]

There is currently no FDA-approved treatment for the dry form of age-related macular degeneration (AMD), which is a leading cause of blindness, and it is linked to the accumulation of toxic lipofuscin pigments in retinal pigment epithelium (RPE).

Inhibiting the production of these harmful lipofuscin bisretinoids, such as A2E, through various pharmacological strategies, including enzyme inhibitors and vitamin A analogs, presents a promising approach for developing treatments for dry AMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological inhibition of lipofuscin accumulation in the retina as a therapeutic strategy for dry AMD treatment. Petrukhin, K.[2021]

Disulfiram (DSF) and its metabolite diethyldithiocarbamate (DDTC) were evaluated against 30 types of bacteria, with DDTC showing notable antibacterial activity specifically against Bacillus anthracis.

The study suggests that while DSF's metabolites do not significantly enhance its antibacterial properties, DDTC can boost the effectiveness of DSF, indicating its potential as an antibiotic adjuvant for treating resistant staph infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibacterial activity of disulfiram and its metabolites. Frazier, KR., Moore, JA., Long, TE.[2019]

Citations

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Oral disulfiram (Antabuse®) has been shown to improve image-forming vision in animal models with retinal degeneration due to its ability to ...

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fightingblindness.org/news/drug-for-alcohol-abuse-may-restore-vision-for-people-with-retinal-diseases-835

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The research team believes the drug may restore vision in people with RP and perhaps other retinal conditions such as age-related macular ...

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A key to restoring sight may be held in a drug that treats ...

They found that nearly blind mice, treated with disulfiram, were much better at detecting images on a computer screen. Mouse retinal ganglion ...

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Antabuse may help revive vision in people with progressive ...

The drug may revive sight in humans with the inherited disease retinitis pigmentosa (RP), and perhaps in other vision disorders, including age- ...

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The Effects of Disulfiram (Antabuse®) on Visual Acuity in ...

Oral disulfiram (Antabuse®) has been shown to improve image-forming vision in animal models with retinal degeneration due to its ability to ...

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fightingblindness.org/news/antabuse-moves-into-clinical-trial-for-people-with-rp-896

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Antabuse may help revive vision in people with progressive ...

The drug may revive sight in humans with the inherited disease retinitis pigmentosa (RP), and perhaps in other vision disorders, including age- ...