Vitamin A Palmitate Supplementation in People With Age-Related Macular Degeneration (and Without Reticular Pseudodrusen) and Delayed Dark Adaptation

Objective:

The objective of this study is to investigate the potential efficacy and safety of vitamin A palmitate dosing in improving dark adaptation in participants with age-related macular degeneration (AMD) and abnormal dark adaptation.

Study Population:

The first cohort consists of five participants with AMD who meet the eligibility criteria. The second cohort will consist of five participants with AMD who meet the eligibility criteria. Up to five additional participants may be accrued in the second cohort to account for participants who withdraw from the study prior to receiving one month of study supplementation for a reason unrelated to an adverse reaction. Up to 18 participants may be enrolled in this study.

Design:

This is a prospective, uncontrolled, single center, pilot study to investigate the potential efficacy and safety of vitamin A palmitate dosing in improving dark adaptation in participants with AMD and abnormal dark adaptation. Participants in the first cohort were instructed to take 16,000 IU of vitamin A palmitate daily for two months. Enrollment for Cohort 1 ended on May 24, 2019. Participants in the second cohort will be instructed to take 48,000 IU of vitamin A palmitate daily for one month. Participants in both cohorts will continue in the study for one month after ending Vitamin A supplementation. Participants in Cohort 1 may enroll into Cohort 2 as long as their last intake of vitamin A palmitate was greater than two months prior to their enrollment into Cohort 2.

Outcome Measures:

For each cohort, the primary outcome is the measurement of dark adaptation parameters (thresholds and kinetics) by the following: dark adaptation times as measured by the AdaptDx comparing before and after vitamin A palmitate supplementation and dark adaptation parameters as measured by the Medmont comparing before and after vitamin A palmitate supplementation. The primary outcome will be assessed at Month 2 in the first cohort and Month 1 in the second cohort. For both cohorts, the secondary outcomes include changes in low luminance visual acuity (LLVA) and changes in patient reported outcomes as measured by the low luminance questionnaire (LLQ). The secondary outcomes also include measurement of dark adaptation parameters (thresholds and kinetics) comparing baseline and one month after completing supplementation (Month 3 in Cohort 1 and Month 2 in Cohort 2).

• INCLUSION CRITERIA:

To be eligible, the following inclusion criteria must be met, where applicable.

• Participant must be 50 years of age or older.
• Participant must understand and sign the protocol s informed consent document.
• Any participant of childbearing potential must be willing to undergo urine pregnancy tests throughout the study.
• Any participant of childbearing potential and any participant able to father children must have (or have a partner who has) had a hysterectomy or vasectomy, be completely abstinent from intercourse, or must agree to practice at least one acceptable method of contraception throughout the course of the study and for one week after study supplement discontinuation. Acceptable methods of contraception include:

• Hormonal contraception (i.e. birth control pills, injected hormones, dermal patch or vaginal ring),
• Intrauterine device,
• Barrier methods (diaphragm, condom) with spermicide, or
• Surgical sterilization (tubal ligation).
• Participants must agree to notify the study investigator or coordinator if any of their doctors initiate a new prescription medication during the course of this study.
• Participant must agree to not take greater than or equal to 8000 IU vitamin A palmitate outside the study supplementation.
• For supplementation eligibility, participant must have normal liver function as demonstrated by the Chemistry 20 panel, or have mild abnormalities not above grade 1 as defined by the Common Terminology Criteria for Adverse Events v4.0 (CTCAE).

Exclusion criteria

A participant is not eligible if any of the following exclusion criteria are present:

• Participant is in another investigational study and actively receiving study therapy.
• Participant is unable to comply with study procedures or follow-up visits.
• Participant is already taking vitamin A palmitate supplements greater than or equal to 8,000 IU.
• Participant has a history of vitamin A deficiency.
• Participant has a condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure and glycemic control).
• Participant has a history of hepatitis or liver failure.
• Participant has chronic gastrointestinal disease.
• Participant will be excluded if the participant has serologic evidence of an active hepatitis infection.
• Participant was in Cohort 1 and took his/her last dose of vitamin A palmitate less than two months prior to enrolling in Cohort 2.

STUDY EYE ELIGIBILITY CRITERIA:

The participant must have at least one eye meeting all inclusion criteria and none of the exclusion criteria listed below.

STUDY EYE INCLUSION CRITERIA:

• The eye must have a best-corrected ETDRS visual acuity score better than or equal to 20/80 (i.e., equal to or better than 54 letters).
• Participant must have at least one large druse.
• Abnormal dark adaptation, which is defined as having an Adapt Dx test with a RIT of 16 minutes or more at the screening visit. This is at least one standard deviation greater than the average normal RIT and includes room to account for variability in testing. If at any point during current testing or under a previous NEI protocol, a participant has exceeded the 40 minute test ceiling, they will have satisfied the inclusion criteria.

STUDY EYE EXCLUSION CRITERIA:

• Presence of advanced macular degeneration with central geographic atrophy or choroidal neovascularization.
• Presence of definite reticular pseudodrusen.
• An ocular condition is present (other than retinal vein occlusion) that, in the opinion of the investigator, might alter visual acuity during the course of the study (e.g., vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, Irvine-Gass Syndrome, etc.).
• Substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by three lines or more (i.e., cataract would be reducing acuity to 20/40 or worse if eye was otherwise normal).
• History of major ocular surgery (e.g. cataract extraction, scleral buckle, any intraocular surgery, etc.) within three months prior to study entry.
• History of YAG (Yttrium-Aluminum Garnet) capsulotomy performed within two months prior to study entry.