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

Not Applicable

Withdrawn

• Conditions: Choroideremia
• Interventions: Dietary Supplement: Vitamin A palmitate

• Registration Number: NCT05045703
• Lead Sponsor: Duke University

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2021-09-07
• Study First Submitted QC: 2021-09-07
• Study First Posted: 2021-09-16
• Study Start: 2023-05
• Status Verified: 2023-06
• Last Update Submitted: 2023-06-27
• Last Update Posted: 2023-06-29
• Primary Completion: 2024-03
• Study Completion: 2024-05

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: Male
• Target Recruitment: Not specified

Inclusion Criteria

• males at least 15 years of age with molecularly-confirmed diagnosis of choroideremia

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Exclusion Criteria

• inability to participate in visual field testing reliably and reproducibly

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Vitamin A palmitate	Vitamin A palmitate	Vitamin A palmitate, 15,000 IU daily for 4 months

Primary Outcome Measures

Name	Time	Method
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-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 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 Outcome Measures

Name	Time	Method
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 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)
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 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 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 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 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

Trial Locations

Locations (1)

Duke Eye Center; 🇺🇸 Durham, North Carolina, United States