Clinical trial NCT03478878: Vitamin A Palmitate Supplementation in Patients With Reticular Pseudodrusen (RPD) and Delayed Dark Adaptation
Official title: An Investigation of Vitamin A Palmitate Supplementation in Patients With Reticular Pseudodrusen (RPD) and Delayed Dark Adaptation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Reticular Pseudodrusen (RPD)
Age-Related Macular Degeneration
Keywords: Eye Examinations
Retinal Pigment Epithelium
Age-Related Macular Degeneration (AMD)
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2018-03-27
Enrollment: 9
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 they eye to adjust to low light. This is known as dark adaptation. This is particularly significant in people with reticular pseudodrusen (RPD). Identifying and watching the early to middle stages of AMD and changes in dark adaptation might help researchers learn to stop the disease before it becomes severe. Taking vitamin A might help improve vision in people with RPD.

Objectives:

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

Eligibility:

Adults ages 50 and older with RPD 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 and last 4-6 hours. 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 20-40 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 reticular pseudodrusen (RPD) and abnormal dark adaptation.

Study Population: The first cohort consists of seven participants with RPD who meet the eligibility criteria. The second cohort will consist of five participants with RPD 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 two months 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 pilot, uncontrolled, prospective, single center study to investigate the potential efficacy and safety of vitamin A palmitate dosing in improving dark adaptation in participants with RPD and abnormal dark adaptation. Participants in the first cohort were instructed to take 16,000 IU of vitamin A palmitate daily for two months. Participants in the second cohort will be instructed to take 48,000 IU of vitamin A palmitate daily for one month. Enrollment for Cohort 1 ended on January 10, 2019. 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 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).

Eligibility criteria: * INCLUSION CRITERIA:

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

1. Participant must be 50 years of age or older.
2. Participant must understand and sign the protocol s informed consent document.
3. Any participant of childbearing potential must be willing to undergo urine pregnancy tests throughout the study.
4. 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).
5. 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.
6. Participant must agree to not take vitamin A palmitate greater than or equal to 8,000 IU outside the study supplementation.
7. 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).
8. Participant must not be pregnant or breast-feeding and must have a negative urine pregnancy test within 24 hours prior to initiation of study medication.

EXCLUSION CRITERIA:

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

1. Participant is in another investigational study and actively receiving study therapy.
2. Participant is unable to comply with study procedures or follow-up visits.
3. Participant is already taking vitamin A palmitate supplements greater than or equal to 8,000 IU.
4. Participant has a history of vitamin A deficiency.
5. 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).
6. Participant has a history of hepatitis or liver failure.
7. Participant has chronic gastrointestinal disease.
8. Participant will be excluded if the participant has serologic evidence of an active hepatitis infection.
9. 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 INCLUSION CRITERIA:

1. 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).
2. Participant must have presence of reticular pseudodrusen on multi-modal imaging.
3. Abnormal dark adaptation, which is defined as having an AdaptDx 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:

1. Presence of advanced macular degeneration with central geographic atrophy or choroidal neovascularization.
2. An ocular condition is present (other than AMD) 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.).
3. 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).
4. History of major ocular surgery (e.g., cataract extraction, scleral buckle, any intraocular surgery, etc.) within three months prior to study entry.
5. History of YAG (Yttrium-Aluminum Garnet) capsulotomy performed within two months prior to study entry.

CHOICE OF STUDY EYE IN CASES OF BILATERAL DISEASE:

If both eyes meet the study eye eligibility criteria described above, the following criteria will be used to select the study eye for the purposes of this investigation:

1. The eye with the better visual acuity will be chosen.
2. If both eyes are equal acuity, the right eye will be arbitrarily chosen as the study eye

Primary outcomes:
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)
timeFrame: Baseline to Month 2 for Cohort 1 and Baseline to Month 1 for Cohort 2
Secondary outcomes:
measure: 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)
timeFrame: Baseline to Month 3 for Cohort 1 and Baseline to Month 2 for Cohort 2
measure: Change in Low Luminance Visual Acuity (LLVA) From Baseline in the Study Eye at the Treatment Completion and Post-Treatment Follow-Up Visits
timeFrame: 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
measure: Change in Low Luminance Questionnaire (LLQ) Composite Score From Baseline at the Treatment Completion and Post-Treatment Follow-Up Visits
timeFrame: 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
measure: Change in Low Luminance Questionnaire (LLQ) Driving Subscale Score From Baseline at the Treatment Completion and Post-Treatment Follow-Up Visits
timeFrame: 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
measure: Change in Low Luminance Questionnaire (LLQ) Extreme Lighting Subscale Score From Baseline at the Treatment Completion and Post-Treatment Follow-Up Visits
timeFrame: 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
measure: Change in Low Luminance Questionnaire (LLQ) Mobility Subscale Score From Baseline at the Treatment Completion and Post-Treatment Follow-Up Visits
timeFrame: 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
measure: Change in Low Luminance Questionnaire (LLQ) Emotional Distress Subscale Score From Baseline at the Treatment Completion and Post-Treatment Follow-Up Visits
timeFrame: 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
measure: Change in Low Luminance Questionnaire (LLQ) General Dim Lighting Subscale Score From Baseline at the Treatment Completion and Post-Treatment Follow-Up Visits
timeFrame: 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
measure: Change in Low Luminance Questionnaire (LLQ) Peripheral Vision Subscale Score From Baseline at the Treatment Completion and Post-Treatment Follow-Up Visits
timeFrame: 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
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Eye Institute (NEI)
name: Emily Y Chew, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.