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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Placebo medication |
|
| Disulfiram | Active Comparator | Disulfiram medication |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Disulfiram 250 mg | Drug | Disulfiram treatment |
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Year 1 |
| Assess the effects of disulfiram on photoreceptor functionality in eyes afflicted with inherited retinal degenerations. |
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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:
Liver function values that fall in the normal range as specified below:
Exclusion Criteria:
Note: study participants cannot receive another investigational drug while participating in this study.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Debarshi Mustafi, MD, PhD | Contact | 206-616-9305 | debarshi@uw.edu |
| Name | Affiliation | Role |
|---|---|---|
| Debarshi Mustafi, MD, PhD | University of Washington | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Washington-South Lake Union Retina Center | Recruiting | Seattle | Washington | 98109 | United States |
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| ID | Term |
|---|---|
| D004221 | Disulfiram |
| ID | Term |
|---|---|
| D004050 | Ditiocarb |
| D013859 | Thiocarbamates |
| D002219 | Carbamates |
| D000144 | Acids, Acyclic |
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Randomized Cross-over study
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| Drug |
Placebo treatment |
|
Evaluate the change in retinal sensitivity as measured by standard and adaptive optics-scanning laser ophthalmoscopy based microperimetry |
| Year 1 |
| D002264 |
| Carboxylic Acids |
| D009930 | Organic Chemicals |
| D004220 | Disulfides |
| D013440 | Sulfides |
| D013457 | Sulfur Compounds |