The Dark-Adapted Retinal Function Response in Choroideremia (DARC) Study

Study Overview
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Brief Summary
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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.

Official Title
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Characterization of Night Vision Impairment in Choroideremia and Short-Term Vitamin A Supplementation: The Dark-Adapted Retinal Function Response in Choroideremia (DARC) Study

Conditions
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Choroideremia

Intervention / Treatment
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* Dietary Supplement: Vitamin A palmitate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 15 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin A palmitate<br>Vitamin A palmitate, 15,000 IU daily for 4 months | Dietary Supplement: Vitamin A palmitate<br>* Vitamin A palmitate, 15,000 IU daily for 4 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in dark-adapted full-field visual field sensitivity | Dark-adapted full-field visual field sensitivity will be measured using the Medmont dark-adapted chromatic perimeter. | 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 | 
| Change in dark-adapted macular visual field sensitivity | Dark-adapted macular visual field sensitivity will be measured using the Medmont dark-adapted chromatic perimeter. | 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 | 
| Change in dark adaptometry | Dark adaptometry will be measured using the MacuLogix AdaptDx dark adaptometer. | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in best corrected visual acuity | Best corrected visual acuity will be measured using the ETDRS chart | 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 | 
| Change in low luminance visual acuity | Low luminance visual acuity will be measured using the ETDRS chart in low luminance conditions | 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 | 
| Change in full-field light-adapted visual field sensitivity | Light-adapted full-field visual field sensitivity will be measured using the Octopus 172-point GATE full-field semi-automated kinetic perimetry (SKP) | 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 | 
| Change in light-adapted macular visual field sensitivity | Light-adapted macular visual field sensitivity will be measured using the Centervue MAIA confocal macular microperimeter | 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 | 
| Change in retinal pigmented epithelium (RPE) atrophy by optical coherence tomography | 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) | 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 | 
| Change in retinal pigmented epithelium (RPE) atrophy by color photography | Retinal pigmented epithelium (RPE) atrophy will be measured using the Optos wide-field color fundus photography (WF-CFP) | 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 | 
| Change in retinal pigmented epithelium (RPE) atrophy by fundus autofluorescence | Retinal pigmented epithelium (RPE) atrophy will be measured using the Optos wide-field fundus auto-fluorescence (WF-FAF) | 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 | 
| Change in retinal pigmented epithelium (RPE) atrophy by fundoscopy | Retinal pigmented epithelium (RPE) atrophy will be assessed by slit lamp biomicroscopy | 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 | 
| Change in liver function | Liver function profile will be measured by laboratory using participant serum samples | Measurements at 0, 4, and 8 months | 
| Change in serum vitamin A levels | Serum vitamin A levels will be measured by laboratory using participant serum samples | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vitamin A, night vision