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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Choroideremia
• Intervention / Treatment: Dietary supplement: Vitamin A palmitate

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Eye Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vitamin A palmitate; Vitamin A palmitate, 15,000 IU daily for 4 months	Dietary supplement: Vitamin A palmitate; Vitamin A palmitate, 15,000 IU daily for 4 months

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Foundation Fighting Blindness

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2023
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: September 7, 2021
• First Submitted That Met QC Criteria: September 7, 2021
• First Posted (Actual): September 16, 2021

Study Record Updates

• Last Update Posted (Actual): June 29, 2023
• Last Update Submitted That Met QC Criteria: June 27, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: vitamin A; night vision
• Additional Relevant MeSH Terms: Eye Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Uveal Diseases; Eye Diseases, Hereditary; Choroid Diseases; Choroideremia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Protective Agents; Micronutrients; Vitamins; Antioxidants; Anticarcinogenic Agents; Vitamin A; Retinol palmitate
• Other Study ID Numbers: Pro00108901

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No