AzTrials
AzTrials

AMDEarly Phase 1NCT03478865

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

A Early Phase 1 study testing Vitamin A palmitate in people with AMD, run by National Eye Institute (NEI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 50 years and older
Conditions the study is for
AMD
What is being tested?
Vitamin A palmitate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
1 siteUnited States
Study dates
20 Apr 2018to 16 Jun 2023
Phase
Early Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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),
Show all 12Show fewer
  • 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).

Who cannot join

  • 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).
Show all 23Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: An Investigation of Vitamin A Palmitate Supplementation in Patients With Age-Related Macular Degeneration (and Without Reticular Pseudodrusen) and Delayed Dark Adaptation

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.

Read more

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.

Read the 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
Being tested
Vitamin A palmitate
Keywords
Eye Examinations, Retinal Pigment Epithelium

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Vitamin A palmitateDrug

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

Study groups in NCT03478865
Study groupRoleWhat they receive
ParticipantsExperimentalParticipants with age-related macular degeneration
Receives: Drug: Vitamin A palmitate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Dark Adaptation Rod Intercept Time (RIT) From Baseline in the Study Eye at the Treatment Completion Visit (Month 2 for Cohort 1 and Month 1 for Cohort 2)

    The mean change in rod intercept time (RIT) in the study eye at the treatment completion visit from baseline was descriptively summarized and assessed using a Student's paired t-test at a two-sided Type I error rate of 5%.

    Measured: Baseline to Month 2 for Cohort 1 and Baseline to Month 1 for Cohort 2

Secondary outcomes (9)
  1. Change in Dark Adaptation Rod Intercept Time (RIT) From Baseline in the Study Eye at the Post-Treatment Follow-Up Visit (Month 3 for Cohort 1 and Month 2 for Cohort 2).

    The mean change in rod intercept time (RIT) in the study eye at the post-treatment follow-up visit from baseline was descriptively summarized and assessed using a Student's paired t-test at a two-sided Type I error rate of 5%.

    Measured: Baseline to Month 3 for Cohort 1 and Baseline to Month 2 for Cohort 2

  2. Change in Low Luminance Visual Acuity (LLVA) From Baseline in the Study Eye at the Treatment Completion and Post-Treatment Follow-Up Visits

    The mean change in low luminance visual acuity (LLVA) in the study eye from baseline at the treatment completion and post-treatment follow-up visits were descriptively summarized.

    Measured: Treatment Completion Visit: Month 2 for Cohort 1 and Month 1 for Cohort 2; Post-Treatment Follow-Up Visit: Month 3 for Cohort 1 and Month 2 for Cohort 2

  3. Change in Low Luminance Questionnaire (LLQ) Composite Score From Baseline at the Treatment Completion and Post-Treatment Follow-Up Visits

    The mean change in low luminance questionnaire (LLQ) composite score from baseline at the treatment completion and post-treatment completion visits were descriptively summarized. LLQ is a 32-item questionnaire relating to difficulty with visual function in low luminance settings. Questions are scored on a range from 0 (indicative of maximum difficulty) to 100 (indicative of no difficulty) in 25 point increments where higher scores indicate better functioning. Each question is assigned to one of six distinct subscales. Applicable questions are averaged to produce (weighted) subscale scores; (weighted) subscale scores are averaged to produce a composite score.

    Measured: Treatment Completion Visit: Month 2 for Cohort 1 and Month 1 for Cohort 2; Post-Treatment Follow-Up Visit: Month 3 for Cohort 1 and Month 2 for Cohort 2

  4. Change in Low Luminance Questionnaire (LLQ) Driving Subscale Score From Baseline at the Treatment Completion and Post-Treatment Follow-Up Visits

    The mean change in low luminance questionnaire (LLQ) driving subscale score from baseline at the treatment completion and post-treatment completion visits were descriptively summarized. LLQ is a 32-item questionnaire relating to difficulty with visual function in low luminance settings. Questions are scored on a range from 0 (indicative of maximum difficulty) to 100 (indicative of no difficulty) in 25 point increments where higher scores indicate better functioning. Each question is assigned to one of six distinct subscales. Applicable questions are averaged to produce (weighted) subscale scores.

    Measured: Treatment Completion Visit: Month 2 for Cohort 1 and Month 1 for Cohort 2; Post-Treatment Follow-Up Visit: Month 3 for Cohort 1 and Month 2 for Cohort 2

  5. Change in Low Luminance Questionnaire (LLQ) Extreme Lighting Subscale Score From Baseline at the Treatment Completion and Post-Treatment Follow-Up Visits

    The mean change in low luminance questionnaire (LLQ) extreme lighting subscale score from baseline at the treatment completion and post-treatment completion visits were descriptively summarized. LLQ is a 32-item questionnaire relating to difficulty with visual function in low luminance settings. Questions are scored on a range from 0 (indicative of maximum difficulty) to 100 (indicative of no difficulty) in 25 point increments where higher scores indicate better functioning. Each question is assigned to one of six distinct subscales. Applicable questions are averaged to produce (weighted) subscale scores.

    Measured: Treatment Completion Visit: Month 2 for Cohort 1 and Month 1 for Cohort 2; Post-Treatment Follow-Up Visit: Month 3 for Cohort 1 and Month 2 for Cohort 2

  6. Change in Low Luminance Questionnaire (LLQ) Mobility Subscale Score From Baseline at the Treatment Completion and Post-Treatment Follow-Up Visits

    The mean change in low luminance questionnaire (LLQ) mobility subscale score from baseline at the treatment completion and post-treatment completion visits were descriptively summarized. LLQ is a 32-item questionnaire relating to difficulty with visual function in low luminance settings. Questions are scored on a range from 0 (indicative of maximum difficulty) to 100 (indicative of no difficulty) in 25 point increments where higher scores indicate better functioning. Each question is assigned to one of six distinct subscales. Applicable questions are averaged to produce (weighted) subscale scores.

    Measured: Treatment Completion Visit: Month 2 for Cohort 1 and Month 1 for Cohort 2; Post-Treatment Follow-Up Visit: Month 3 for Cohort 1 and Month 2 for Cohort 2

  7. Change in Low Luminance Questionnaire (LLQ) Emotional Distress Subscale Score From Baseline at the Treatment Completion and Post-Treatment Follow-Up Visits

    The mean change in low luminance questionnaire (LLQ) emotional distress subscale score from baseline at the treatment completion and post-treatment completion visits were descriptively summarized. LLQ is a 32-item questionnaire relating to difficulty with visual function in low luminance settings. Questions are scored on a range from 0 (indicative of maximum difficulty) to 100 (indicative of no difficulty) in 25 point increments where higher scores indicate better functioning. Each question is assigned to one of six distinct subscales. Applicable questions are averaged to produce (weighted) subscale scores.

    Measured: Treatment Completion Visit: Month 2 for Cohort 1 and Month 1 for Cohort 2; Post-Treatment Follow-Up Visit: Month 3 for Cohort 1 and Month 2 for Cohort 2

  8. Change in Low Luminance Questionnaire (LLQ) General Dim Lighting Subscale Score From Baseline at the Treatment Completion and Post-Treatment Follow-Up Visits

    The mean change in low luminance questionnaire (LLQ) general dim lighting subscale score from baseline at the treatment completion and post-treatment completion visits were descriptively summarized. LLQ is a 32-item questionnaire relating to difficulty with visual function in low luminance settings. Questions are scored on a range from 0 (indicative of maximum difficulty) to 100 (indicative of no difficulty) in 25 point increments where higher scores indicate better functioning. Each question is assigned to one of six distinct subscales. Applicable questions are averaged to produce (weighted) subscale scores.

    Measured: Treatment Completion Visit: Month 2 for Cohort 1 and Month 1 for Cohort 2; Post-Treatment Follow-Up Visit: Month 3 for Cohort 1 and Month 2 for Cohort 2

  9. Change in Low Luminance Questionnaire (LLQ) Peripheral Vision Subscale Score From Baseline at the Treatment Completion and Post-Treatment Follow-Up Visits

    The mean change in low luminance questionnaire (LLQ) peripheral vision subscale score from baseline at the treatment completion and post-treatment completion visits were descriptively summarized. LLQ is a 32-item questionnaire relating to difficulty with visual function in low luminance settings. Questions are scored on a range from 0 (indicative of maximum difficulty) to 100 (indicative of no difficulty) in 25 point increments where higher scores indicate better functioning. Each question is assigned to one of six distinct subscales. Applicable questions are averaged to produce (weighted) subscale scores.

    Measured: Treatment Completion Visit: Month 2 for Cohort 1 and Month 1 for Cohort 2; Post-Treatment Follow-Up Visit: Month 3 for Cohort 1 and Month 2 for Cohort 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Mar 2018
  2. Study start20 Apr 2018
  3. Primary completion16 Jun 2023
  4. Study completion16 Jun 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03478865
Sponsor's protocol ID
180067
Other IDs
18-EI-0067
Status last verified
Mar 2024
First submitted
15 Mar 2018
Last updated
15 Apr 2025
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 37315571

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Vitamin A palmitate in people with AMD, run by National Eye Institute (NEI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Dark Adaptation Rod Intercept Time (RIT) From Baseline in the Study Eye at the Treatment Completion Visit (Month 2 for Cohort 1 and Month 1 for Cohort 2) (time frame: Baseline to Month 2 for Cohort 1 and Baseline to Month 1 for Cohort 2). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03478865, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2025.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in