Disulfiram for Treatment of Retinal Degeneration

NCT05626920 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: STUDY00015434
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Aberrant retinoic acid signaling driven by the degenerating outer retina leads to pathological changes to the inner retina. The resulting hyperactivity of retinal ganglion cells leads to further diminution of the remaining vision in those afflicted with inherited retinal diseases. Inhibition of this pathway has led to improved visual function in murine models of retinal degeneration. This can be accomplished in humans with the FDA-approved irreversible inhibitor of aldehyde dehydrogenases, disulfiram.

Conditions

Inherited Retinal Dystrophy Primarily Involving Sensory Retina

Outcome Measures

Primary Outcomes (1)

• Assess the effects of disulfiram on retinal sensitivity in eyes afflicted with inherited retinal degenerations

  Evaluate change in contrast sensitivity measured by spatial contrast contrast sensitivity testing between disulfiram and placebo arms

  Year 1

Secondary Outcomes (2)

• Assess the effects of disulfiram on visual acuity in eyes afflicted with inherited retinal degenerations.

  Year 1

• Assess the effects of disulfiram on photoreceptor functionality in eyes afflicted with inherited retinal degenerations.

  Year 1

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo medication

Drug: Placebo

Disulfiram

ACTIVE COMPARATOR

Disulfiram medication

Drug: Disulfiram 250 mg

Interventions

Disulfiram 250 mg DRUG

Disulfiram treatment

Disulfiram

Placebo DRUG

Placebo treatment

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Only one eye per subject should be identified as the study eye. The study eye must meet the following criteria:
• Best corrected ETDRS visual acuity letter score ≥ 70 (i.e., 20/40 or better) within 30 days of enrollment.
• Goldmann visual field exhibiting constriction of visual fields to 10 degrees centrally
• Able and willing to provide informed consent
• Willing and able to abstain from alcohol consumption for the duration of the study and the 2 weeks preceding it and 2 weeks following the study end point
• Liver function values that fall in the normal range as specified below:
• Alanine transaminase (ALT): less than 40 IU/L
• Aspartate transaminase (AST): less than 40 IU/L
• Alkaline phosphatase (ALP): less than 300 IU/L
• Albumin (Alb): less than 50 g/L
• Total Protein: less than 80 g/L
• Total Bilirubin: less than 30 umol/L

You may not qualify if:

• A condition that, in the opinion of the investigator, would preclude participation in the study, e.g., alcohol dependence, 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.
• An ocular condition, other than inherited retinal degeneration, is present such that, in the opinion of the investigator, visual acuity might be affected (e.g., foveal atrophy, pigment abnormalities, dense subfoveal hard exudates, non-retinal conditions such as epiretinal membrane or vitreo-macular traction, vein occlusion, uveitis or other ocular inflammatory diseases such as neovascular glaucoma, etc).
• 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. Women who are potential study participants should be questioned about the potential for pregnancy. Investigator judgment will be used to determine when a pregnancy test is needed.
• Participants who expect to move out of the area of the clinical center during the 8 months of the study

Sponsors & Collaborators

• University of Washington: lead

Study Sites (1)

University of Washington-South Lake Union Retina Center

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Interventions

Disulfiram

Intervention Hierarchy (Ancestors)

Ditiocarb; Thiocarbamates; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Disulfides; Sulfides; Sulfur Compounds

Study Officials

• Debarshi Mustafi, MD, PhD

  University of Washington

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Debarshi Mustafi, MD, PhD

CONTACT

206-616-9305; debarshi@uw.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor: Dept of Ophthamology

Model Details: Randomized Cross-over study

Study Record Dates

• First Submitted: November 15, 2022
• First Posted: November 25, 2022
• Study Start: May 3, 2026
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: May 5, 2026

Record last verified: 2026-04

Locations

US (1)