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

NCT ID: NCT03478865

Last Updated: 2025-04-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-20
• Study Completion Date: 2023-06-16

Brief Summary

Background:

Age-related macular degeneration (AMD) is an eye disease. It is the leading cause of vision loss in people over 55 in the U.S. Changes in the eye can make it difficult for the eye to adjust to low light. This is known as dark adaptation. Identifying and watching the early to middle stages of AMD and changes in dark adaptation might help researchers develop new treatments to stop the disease before it becomes severe. Taking vitamin A might help improve vision in people with AMD.

Objectives:

To see if taking 16,000 IU of vitamin A per day improves vision in people with AMD. Also to improve understanding of AMD and associated dark adaptation.

Eligibility:

Adults ages 50 and older with AMD and normal liver function

Design:

Participants will be screened with:

Medical and eye disease history

Eye exam: The pupil will be dilated with eye drops. Pictures will be taken of the retina and the inside of the eye.

Including the screening visit, participants will have at least 5 visits. They will be about once a month over 6 months. Visits include:

Questions about eye problems in certain light

Eye exam

Blood and urine tests

Dark adaptation protocol: Participants will sit at a machine in a dark room. They will look into the machine and push a button when they see a light. This lasts 20-30 minutes.

Participants will take a vitamin A supplement by mouth once a day for 2 months. They will record when they take the pills in a diary.

Detailed Description

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).

Conditions

AMD

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Participants

Participants with age-related macular degeneration

Group Type: EXPERIMENTAL

Vitamin A palmitate

Intervention Type: DRUG

Provide vitamin A to participants with pre/post assessments of vision.

Interventions

Vitamin A palmitate

Provide vitamin A to participants with pre/post assessments of vision.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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).

• 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.

Exclusion Criteria

• 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:

• 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.

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Eye Institute (NEI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emily Y Chew, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Eye Institute (NEI)

Locations

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Countries

United States

References

Pfau K, Jeffrey BG, Cukras CA. LOW-DOSE SUPPLEMENTATION WITH RETINOL IMPROVES RETINAL FUNCTION IN EYES WITH AGE-RELATED MACULAR DEGENERATION BUT WITHOUT RETICULAR PSEUDODRUSEN. Retina. 2023 Sep 1;43(9):1462-1471. doi: 10.1097/IAE.0000000000003840.

Reference Type: RESULT

PMID: 37315571 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2018-EI-0067.html

NIH Clinical Center Detailed Web Page

Other Identifiers

18-EI-0067

Identifier Type: -

Identifier Source: secondary_id

180067

Identifier Type: -

Identifier Source: org_study_id