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NCT03478865

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

Completed EARLY_PHASE1 Results posted Last updated 15 April 2025
What this trial tests

EARLY_PHASE1 trial testing Vitamin A palmitate in AMD in 8 participants. Completed in 16 June 2023.

Timeline
20 April 2018
Primary endpoint
16 June 2023
16 June 2023

Quick facts

Lead sponsorNational Eye Institute (NEI)
PhaseEARLY_PHASE1
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment8
Start date20 April 2018
Primary completion16 June 2023
Estimated completion16 June 2023
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Eye Institute (NEI)

Who can join

50 and older, any sex, with AMD. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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) Primary · Baseline to Month 2 for Cohort 1 and Baseline to 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%.

Baseline Visit
GroupValue95% CI
Cohort 125.12± 10.755
Cohort 220.03± 6.793
Treatment Completion Visit
GroupValue95% CI
Cohort 122.58± 8.219
Cohort 219.77± 7.753
Change from Baseline at the Treatment Completion Visit
GroupValue95% CI
Cohort 1-2.54± 4.322
Cohort 2-0.27± 1.767
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). Secondary · Baseline to Month 3 for Cohort 1 and Baseline to 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%.

Baseline Visit
GroupValue95% CI
Cohort 125.12± 10.755
Cohort 220.03± 6.793
Post-Treatment Follow-Up Visit
GroupValue95% CI
Cohort 121.56± 6.271
Cohort 223.27± 12.847
Change from Baseline at the Post-Treatment Follow-Up Visit
GroupValue95% CI
Cohort 1-3.56± 7.793
Cohort 23.23± 6.512
Change in Low Luminance Visual Acuity (LLVA) From Baseline in the Study Eye at the Treatment Completion and Post-Treatment Follow-Up Visits Secondary · 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

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.

Baseline Visit
GroupValue95% CI
Cohort 166.8± 16.22
Cohort 256.3± 16.17
Treatment Completion Visit
GroupValue95% CI
Cohort 171.6± 11.41
Cohort 259.3± 16.01
Change from Baseline at the Treatment Completion Visit
GroupValue95% CI
Cohort 14.8± 17.31
Cohort 23.0± 1.73
Post-Treatment Follow-Up Visit
GroupValue95% CI
Cohort 169.8± 6.69
Cohort 259.3± 17.01
Change from Baseline at the Post-Treatment Follow-Up Visit
GroupValue95% CI
Cohort 13.0± 14.88
Cohort 23.0± 2.00
Change in Low Luminance Questionnaire (LLQ) Composite Score From Baseline at the Treatment Completion and Post-Treatment Follow-Up Visits Secondary · 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

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; (we

Baseline Visit
GroupValue95% CI
Cohort 186.35± 17.521
Cohort 286.79± 11.431
Treatment Completion Visit
GroupValue95% CI
Cohort 187.38± 17.420
Cohort 286.13± 9.958
Post-Treatment Follow-Up Visit
GroupValue95% CI
Cohort 184.83± 19.142
Cohort 288.73± 7.382
Change from Baseline at the Treatment Completion Visit
GroupValue95% CI
Cohort 11.03± 1.087
Cohort 2-0.66± 2.815
Change from Baseline at the Post-Treatment Follow-Up Visit
GroupValue95% CI
Cohort 1-1.51± 3.283
Cohort 21.93± 5.435
Change in Low Luminance Questionnaire (LLQ) Driving Subscale Score From Baseline at the Treatment Completion and Post-Treatment Follow-Up Visits Secondary · 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

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 scor

Baseline Visit
GroupValue95% CI
Cohort 186.00± 20.433
Cohort 268.33± 37.859
Treatment Completion Visit
GroupValue95% CI
Cohort 187.00± 17.889
Cohort 255.00± 36.056
Post-Treatment Follow-Up Visit
GroupValue95% CI
Cohort 184.00± 22.192
Cohort 263.33± 33.292
Change from Baseline at the Treatment Completion Visit
GroupValue95% CI
Cohort 11.00± 8.944
Cohort 2-13.33± 5.774
Change from Baseline at the Post-Treatment Follow-Up Visit
GroupValue95% CI
Cohort 1-2.00± 4.472
Cohort 2-5.00± 5.000
Change in Low Luminance Questionnaire (LLQ) Extreme Lighting Subscale Score From Baseline at the Treatment Completion and Post-Treatment Follow-Up Visits Secondary · 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

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) subs

Baseline Visit
GroupValue95% CI
Cohort 181.25± 18.880
Cohort 273.96± 26.578
Treatment Completion Visit
GroupValue95% CI
Cohort 184.38± 20.492
Cohort 277.08± 25.259
Post-Treatment Follow-Up Visit
GroupValue95% CI
Cohort 178.75± 20.420
Cohort 280.83± 12.521
Change from Baseline at the Treatment Completion Visit
GroupValue95% CI
Cohort 13.13± 5.846
Cohort 23.13± 5.413
Change from Baseline at the Post-Treatment Follow-Up Visit
GroupValue95% CI
Cohort 1-2.50± 6.775
Cohort 26.88± 26.612
Change in Low Luminance Questionnaire (LLQ) Mobility Subscale Score From Baseline at the Treatment Completion and Post-Treatment Follow-Up Visits Secondary · 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

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 sco

Baseline Visit
GroupValue95% CI
Cohort 188.33± 16.245
Cohort 296.53± 3.182
Treatment Completion Visit
GroupValue95% CI
Cohort 190.00± 14.006
Cohort 297.22± 2.406
Post-Treatment Follow-Up Visit
GroupValue95% CI
Cohort 188.33± 15.975
Cohort 297.22± 2.406
Change from Baseline at the Treatment Completion Visit
GroupValue95% CI
Cohort 11.67± 2.282
Cohort 20.69± 5.243
Change from Baseline at the Post-Treatment Follow-Up Visit
GroupValue95% CI
Cohort 10.00± 2.946
Cohort 20.69± 5.243
Change in Low Luminance Questionnaire (LLQ) Emotional Distress Subscale Score From Baseline at the Treatment Completion and Post-Treatment Follow-Up Visits Secondary · 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

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) su

Baseline Visit
GroupValue95% CI
Cohort 195.00± 8.149
Cohort 297.22± 4.811
Treatment Completion Visit
GroupValue95% CI
Cohort 193.75± 10.825
Cohort 295.14± 4.337
Post-Treatment Follow-Up Visit
GroupValue95% CI
Cohort 193.75± 10.825
Cohort 297.92± 3.608
Change from Baseline at the Treatment Completion Visit
GroupValue95% CI
Cohort 1-1.25± 2.795
Cohort 2-2.08± 3.608
Change from Baseline at the Post-Treatment Follow-Up Visit
GroupValue95% CI
Cohort 1-1.25± 2.795
Cohort 20.69± 1.203
Change in Low Luminance Questionnaire (LLQ) General Dim Lighting Subscale Score From Baseline at the Treatment Completion and Post-Treatment Follow-Up Visits Secondary · 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

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)

Baseline Visit
GroupValue95% CI
Cohort 182.50± 26.087
Cohort 290.28± 2.406
Treatment Completion Visit
GroupValue95% CI
Cohort 184.17± 24.008
Cohort 295.14± 4.337
Post-Treatment Follow-Up Visit
GroupValue95% CI
Cohort 182.50± 25.069
Cohort 293.06± 6.365
Change from Baseline at the Treatment Completion Visit
GroupValue95% CI
Cohort 11.67± 2.282
Cohort 24.86± 4.337
Change from Baseline at the Post-Treatment Follow-Up Visit
GroupValue95% CI
Cohort 10.00± 2.946
Cohort 22.78± 4.811
Change in Low Luminance Questionnaire (LLQ) Peripheral Vision Subscale Score From Baseline at the Treatment Completion and Post-Treatment Follow-Up Visits Secondary · 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

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) sub

Baseline Visit
GroupValue95% CI
Cohort 185.00± 22.361
Cohort 294.44± 9.623
Treatment Completion Visit
GroupValue95% CI
Cohort 185.00± 22.361
Cohort 297.22± 4.811
Post-Treatment Follow-Up Visit
GroupValue95% CI
Cohort 181.67± 25.276
Cohort 2100.00± 0.000
Change from Baseline at the Treatment Completion Visit
GroupValue95% CI
Cohort 10.00± 0.000
Cohort 22.78± 4.811
Change from Baseline at the Post-Treatment Follow-Up Visit
GroupValue95% CI
Cohort 1-3.33± 7.454
Cohort 25.56± 9.623

Adverse events — posted to ClinicalTrials.gov

Time frame: Participants enrolled are assessed for AEs starting at Baseline through study completion (Month 3 for Cohort 1 and Month 2 for Cohort 2).. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1
Serious: 0/5 (0%)
Deaths: 0/5
Cohort 2
Serious: 0/3 (0%)
Deaths: 0/3
Other adverse events (10 terms — click to expand)

ReactionSystemCohort 1Cohort 2
CataractEye disorders
Eye irritationEye disorders
Lacrimal disorderEye disorders
NauseaGastrointestinal disorders
SwellingGeneral disorders
Blood pressure increasedInvestigations
Blood uric acid increasedInvestigations
MyalgiaMusculoskeletal and connective tissue disorders
Prostatic massReproductive system and breast disorders
Visual ImpairmentEye disorders

Data from ClinicalTrials.gov NCT03478865 adverse events section.

Sponsor's own description

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.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

  1. The Role of Vitamin A in Retinal Diseases.
    Sajovic J, Meglič A, Glavač D, Markelj Š, et al · · 2022 · cited 52× · PMID 35162940 · DOI 10.3390/ijms23031014
  2. Inherited Retinal Dystrophies: Role of Oxidative Stress and Inflammation in Their Physiopathology and Therapeutic Implications.
    Pinilla I, Maneu V, Campello L, Fernández-Sánchez L, et al · · 2022 · cited 30× · PMID 35739983 · DOI 10.3390/antiox11061086
  3. Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration.
    Evans JR, Lawrenson JG. · · 2023 · cited 29× · PMID 37702300 · DOI 10.1002/14651858.cd000254.pub5
  4. Abstractband DOG 2022.
    · 2022 · cited 1× · PMID 36136142 · DOI 10.1007/s00347-022-01723-2
  5. Tracking Systemic and Ocular Vitamin A.
    Montenegro D, Zhao J, Kim H, Cheng S, et al · · 2026 · PMID 41597238 · DOI 10.3390/cells15020163

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