Choroideremia
Conditions
Keywords
vitamin A, night vision
Brief summary
Choroideremia (CHM) is an inherited retinal disorder that causes progressive vision loss, ultimately leading to complete blindness. The first symptom is generally night blindness, although, to date, little is known about the extent, type, pattern, and progression of dark-adapted visual function measures in CHM patients. We hypothesize that one of the key events causing night blindness in CHM is deficiency in the chromophore of the rod visual pigment, rhodopsin. We propose that this deficiency is at least in part due to inadequate delivery of vitamin A (all-trans-retinol) to the photoreceptors (PRs) from the ailing retinal pigment epithelium (RPE), characteristic of CHM. We hypothesize that increased availability of vitamin A would potentiate its entry into the RPE-mediated visual cycle, ultimately enabling delivery to the PRs. This would in turn allow rods to perform better by partially overcoming the RPE damage and the impaired chromophore recycling that we postulate exists in CHM. The goals of this proposal are: (1) to test the hypothesis that oral vitamin A supplementation can improve night time and peripheral vision in CHM patients, and (2) to provide detailed characterization of dark-adapted visual function outcome measures to guide interventional CHM trials.
Interventions
DIETARY_SUPPLEMENTVitamin A palmitate
Vitamin A palmitate, 15,000 IU daily for 4 months
Sponsors
Foundation Fighting Blindness
Duke University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
15 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* males at least 15 years of age with molecularly-confirmed diagnosis of choroideremia
Exclusion criteria
* inability to participate in visual field testing reliably and reproducibly
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in dark-adapted full-field visual field sensitivity | Measurements at 0, 4, and 8 months. The 0 months measurement will serve as the baseline. The 4 month measurement will assess change due to vitamin A supplementation. The 8 month measurement will assess reversal of this change following washout period | Dark-adapted full-field visual field sensitivity will be measured using the Medmont dark-adapted chromatic perimeter. |
| Change in dark-adapted macular visual field sensitivity | Measurements at 0, 4, and 8 months. The 0 months measurement will serve as the baseline. The 4 month measurement will assess change due to vitamin A supplementation. The 8 month measurement will assess reversal of this change following washout period | Dark-adapted macular visual field sensitivity will be measured using the Medmont dark-adapted chromatic perimeter. |
| Change in dark adaptometry | Measurements at 0, 4, and 8 months. The 0 months measurement will serve as the baseline. The 4 month measurement will assess change due to vitamin A supplementation. The 8 month measurement will assess reversal of this change following washout period | Dark adaptometry will be measured using the MacuLogix AdaptDx dark adaptometer. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in light-adapted macular visual field sensitivity | Measurements at 0, 4, and 8 months. The 0 months measurement will serve as the baseline. The 4 month measurement will assess change due to vitamin A supplementation. The 8 month measurement will assess reversal of this change following washout period | Light-adapted macular visual field sensitivity will be measured using the Centervue MAIA confocal macular microperimeter |
| Change in retinal pigmented epithelium (RPE) atrophy by optical coherence tomography | Measurements at 0, 4, and 8 months. The 0 months measurement will serve as the baseline. The 4 month measurement will assess change due to vitamin A supplementation. The 8 month measurement will assess reversal of this change following washout period | Retinal pigmented epithelium (RPE) atrophy will be measured using the Spectralis macular spectral domain optical coherence tomography (SD-OCT) with and without enhanced depth imaging (EDI) |
| Change in retinal pigmented epithelium (RPE) atrophy by color photography | Measurements at 0, 4, and 8 months. The 0 months measurement will serve as the baseline. The 4 month measurement will assess change due to vitamin A supplementation. The 8 month measurement will assess reversal of this change following washout period | Retinal pigmented epithelium (RPE) atrophy will be measured using the Optos wide-field color fundus photography (WF-CFP) |
| Change in best corrected visual acuity | Measurements at 0, 4, and 8 months. The 0 months measurement will serve as the baseline. The 4 month measurement will assess change due to vitamin A supplementation. The 8 month measurement will assess reversal of this change following washout period | Best corrected visual acuity will be measured using the ETDRS chart |
| Change in retinal pigmented epithelium (RPE) atrophy by fundoscopy | Measurements at 0, 4, and 8 months. The 0 months measurement will serve as the baseline. The 4 month measurement will assess change due to vitamin A supplementation. The 8 month measurement will assess reversal of this change following washout period | Retinal pigmented epithelium (RPE) atrophy will be assessed by slit lamp biomicroscopy |
| Change in liver function | Measurements at 0, 4, and 8 months | Liver function profile will be measured by laboratory using participant serum samples |
| Change in serum vitamin A levels | Measurements at 0, 4, and 8 months. The 0 months measurement will serve as the baseline. The 4 month measurement will assess change due to vitamin A supplementation. The 8 month measurement will assess reversal of this change following washout period | Serum vitamin A levels will be measured by laboratory using participant serum samples |
| Change in retinal pigmented epithelium (RPE) atrophy by fundus autofluorescence | Measurements at 0, 4, and 8 months. The 0 months measurement will serve as the baseline. The 4 month measurement will assess change due to vitamin A supplementation. The 8 month measurement will assess reversal of this change following washout period | Retinal pigmented epithelium (RPE) atrophy will be measured using the Optos wide-field fundus auto-fluorescence (WF-FAF) |
| Change in low luminance visual acuity | Measurements at 0, 4, and 8 months. The 0 months measurement will serve as the baseline. The 4 month measurement will assess change due to vitamin A supplementation. The 8 month measurement will assess reversal of this change following washout period | Low luminance visual acuity will be measured using the ETDRS chart in low luminance conditions |
| Change in full-field light-adapted visual field sensitivity | Measurements at 0, 4, and 8 months. The 0 months measurement will serve as the baseline. The 4 month measurement will assess change due to vitamin A supplementation. The 8 month measurement will assess reversal of this change following washout period | Light-adapted full-field visual field sensitivity will be measured using the Octopus 172-point GATE full-field semi-automated kinetic perimetry (SKP) |
Countries
United States
Outcome results
None listed