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Disulfiram for Treatment of Retinal Degeneration

Primary Purpose

Inherited Retinal Dystrophy Primarily Involving Sensory Retina

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Disulfiram 250 mg
Placebo
Sponsored by
University of Washington
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Inherited Retinal Dystrophy Primarily Involving Sensory Retina

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age ≥18 years Only those with a clinical diagnosis of inherited retinal degeneration. When available, supporting genetic diagnosis form a CLIA approved lab will be further considered for inclusion. 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 Exclusion Criteria: 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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Placebo Comparator

    Active Comparator

    Arm Label

    Placebo

    Disulfiram

    Arm Description

    Placebo medication

    Disulfiram medication

    Outcomes

    Primary Outcome Measures

    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

    Secondary Outcome Measures

    Assess the effects of disulfiram on visual acuity in eyes afflicted with inherited retinal degenerations.
    Evaluate change in best corrected visual acuity assessed by ETDRS chart testing between disulfiram and placebo arms
    Assess the effects of disulfiram on photoreceptor functionality in eyes afflicted with inherited retinal degenerations.
    Evaluate the change in retinal sensitivity as measured by standard and adaptive optics-scanning laser ophthalmoscopy based microperimetry

    Full Information

    First Posted
    November 15, 2022
    Last Updated
    May 9, 2023
    Sponsor
    University of Washington
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05626920
    Brief Title
    Disulfiram for Treatment of Retinal Degeneration
    Official Title
    A Cross-over Randomized Control Trial to Evaluate the Retinaldehyde Dehydrogenase Inhibitor, Disulfiram, in Improving Retinal Sensitivity in Eyes Affected by Inherited Retinal Degeneration
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    June 2023 (Anticipated)
    Primary Completion Date
    June 2024 (Anticipated)
    Study Completion Date
    September 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    University of Washington

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Inherited Retinal Dystrophy Primarily Involving Sensory Retina

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Crossover Assignment
    Model Description
    Randomized Cross-over study
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    30 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Placebo medication
    Arm Title
    Disulfiram
    Arm Type
    Active Comparator
    Arm Description
    Disulfiram medication
    Intervention Type
    Drug
    Intervention Name(s)
    Disulfiram 250 mg
    Intervention Description
    Disulfiram treatment
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Placebo treatment
    Primary Outcome Measure Information:
    Title
    Assess the effects of disulfiram on retinal sensitivity in eyes afflicted with inherited retinal degenerations
    Description
    Evaluate change in contrast sensitivity measured by spatial contrast contrast sensitivity testing between disulfiram and placebo arms
    Time Frame
    Year 1
    Secondary Outcome Measure Information:
    Title
    Assess the effects of disulfiram on visual acuity in eyes afflicted with inherited retinal degenerations.
    Description
    Evaluate change in best corrected visual acuity assessed by ETDRS chart testing between disulfiram and placebo arms
    Time Frame
    Year 1
    Title
    Assess the effects of disulfiram on photoreceptor functionality in eyes afflicted with inherited retinal degenerations.
    Description
    Evaluate the change in retinal sensitivity as measured by standard and adaptive optics-scanning laser ophthalmoscopy based microperimetry
    Time Frame
    Year 1

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Age ≥18 years Only those with a clinical diagnosis of inherited retinal degeneration. When available, supporting genetic diagnosis form a CLIA approved lab will be further considered for inclusion. 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 Exclusion Criteria: 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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Debarshi Mustafi, MD, PhD
    Phone
    206-616-9305
    Email
    debarshi@uw.edu
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Debarshi Mustafi, MD, PhD
    Organizational Affiliation
    University of Washington
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

    Disulfiram for Treatment of Retinal Degeneration

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