The Zeaxanthin and Visual Function Study

Randomized, Double Blind, Lutein Controlled Study of Zeaxanthin and Visual Function in Atrophic Age Related Macular Degeneration Patients

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00564902

Acronym

ZVF

Enrollment

Registered

2007-11-29

Start date

2007-11-30

Completion date

2009-06-30

Last updated

2012-03-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Age Related Macular Degeneration, Cognition Disorders

Keywords

Macular Pigment Optical Density, Skin Carotenoids, Lipofuscin, Photostress (Glare Recovery), Visual Field Progression, Contrast Sensitivity, Color Vision, Cognitive Function

Brief summary

To evaluate if supplementation of zeaxanthin (with or without Lutein) is beneficial to patients with early and moderate Atrophic Age Related Macular Degeneration.

Detailed description

To evaluate whether or not zeaxanthin supplementation raises macular pigment optical density (MPOD). Previous research has shown MPOD to mirror visual benefits for patients with age related atrophic macular degeneration (AMD) having visual symptoms (decreased visual acuity, contrast sensitivity, photostress glare recovery and National Eye Institute Visual Function Questionnaire 25 scores), but lower risk National Eye Institute (NEI) / Age Related Eye Disease Study (AREDS) characteristics.

Interventions

DRUG3R 3'R Zeaxanthin

8 mg per day during 12 months

DIETARY_SUPPLEMENTLutein

9 mg of Lutein during 12 months

DIETARY_SUPPLEMENTLutein and Zeaxanthin

8 mg of lutein and 8 mg of Zeaxanthin administered during 12 months

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

SUPPORTIVE_CARE

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

45 Years to 90 Years

Healthy volunteers

Inclusion criteria

* diagnosis of atrophic AMD (ICD9 362.51) by stereo bio-ophthalmoscopy and at least one vision degrading visual-psychophysical abnormality associated with AMD in one or both eyes. * clear non-lenticular ocular media (cornea, aqueous and vitreous) * free of advanced glaucoma and diabetes or any other ocular or systemic disease that could affect central or parafoveal macula visual function

Exclusion criteria

* high risk retinal characteristics for advanced AMD or advanced AMD for which existing medical / surgical options are available * presence of ophthalmologically significant active exudative, AMD pathology by fluorescein angiography but also a single large drusen, \>15, multiple intermediate drusen, parafoveal geographic atrophy or loss of vision in one eye due to advanced AMD * recent (within 6 months) cataract or retinal surgery * taking photosensitizing drugs such as phenothiazines and chloroquine * having taken lutein or zeaxanthin supplements within the past six months.

Design outcomes

Primary

Measure	Time frame	Description
Macular Pigment Optical Density	4 months	Replicate measures of foveal 1 degree estimated central MPOD were evaluated with the Quantify® MPS 9000 macular pigment screener, a modified heterochromic flicker photometer (HFP). It employs alternating blue and green flickering LED's and fixation on a 1 degree target, so that a representative measurement at 0.5 degree off center from the fovea is calculated. The method has good repeatability (r = 0.97) and the data are comparable with an objective optical method based on retinal reflectometry (r = 0.78).

Secondary

Measure	Time frame	Description
Early Treatment Diabetic Retinopathy Study Distance Visual Acuity	12 months	Black and 10% contrast near reading visual acuity was assessed with a Colenbrander Mixed Contrast Reading Card with LogMAR letters (#4031, Precision Vision, LaSalle, Illinois). We determined single letter acuity on an ordinal VAS (Visual Acuity Scale). The largest letters were 0.05 LogMAR with a VAS = 35 while the most difficult smallest letters were LogMar 1.25 or VAS 105. The test card was held at 40 cm with best monocular refraction, and both low and high contrast letter acuity were assessed.
Glare Recovery	12 Months	Photostress glare recovery test involves exposing an individual eye to intense light, or retinal bleach, for a set duration of time and measuring the time taken for visual acuity to recover to a predetermined level. Glare photo-stress recovery (in seconds) following 30 seconds of continuous retinal bleach, was assessed using 2 line supra-threshold low contrast randomly presented Landolt Cs using the KOWA AS14B Night Vision Tester (KOWA Optimed, Tokyo, Japan).
SHAPE Discrimination	12 months	We determined the target deformation detection thresholds, or amplitude of the minimum detectable distortion of a 1 degree foveal circular target. The peak spatial frequency of RF (radial frequency) patterns was 5 cyc/deg; the radial modulation frequency was 8 cyc/360°; mean radii were 0.5°, 1°, 2.0°, or 2.5°; and stimulus contrast was 80%. The highest % modulation score possible is 0.13 while the easiest (lowest score) was 10% modulation.
6.5 Degrees Tritan Threshold	12 months	The ChromaTest© is a computerized psychophysical test of protan and tritan color thresholds against age-corrected data. The computer finds the endpoint of the test by a Modified Binary Search method; if response is correct, on the next presentation the color difference between letter and background is halved. If response is incorrect, the color -contrast is doubled. Incorrect responses prolong the test, but do not influence the final threshold. This method of determining thresholds leads to finite steps which reach a plateau at the color contrast sensitivity threshold.
100% Kinetic Field	12 Months	Scotomas within the central 20 degree central macula visual field sensitivity was assessed at 5 contrast levels (20, 40, 60, 80, and full contrast). A yellow wavelength stimulus avoided confounding by the lens. Subjects outlined the boundaries of their scotoma(s) on an area-integrating and recording touch flat- screen RGB monitor displaying a central fixation point and movable horizontal/vertical raster lines. The computer calculated summed area of the scotoma(s) with arbitrary scaling from 6000 (dense scotoma) to 0 relative units (absence of scotoma).
Contrast Sensitivity Function Photopic Distance	12 Months	Distance photopic contrast sensitivity function (CSF) at 5 spatial frequencies (1.5, 3, 6, 12 & 20 cc/deg) was determined with the Functional Vision Analyzer® (Stereo Optical Co, Inc, Chicago, IL). Contrast sensitivity readings are shown as a curve. Visual acuity is plotted along the horizontal axis and contrast sensitivity along the vertical axis. Among the normally sighted people, both visual acuity and contrast sensitivity have a wide range of variation.Low population CSF is 0-200 units; normal population CSF is 200-300 units and suprathreshold CSF is 300+ units.

Countries

United States

Participant flow

Recruitment details

Subjects were patients in the Ophthalmology/Optometry Clinic North Chicago DVA Medical Center (now the James A. Lovell Federal Health Center)with early and moderate AMD retinopathy up to, but not including,high risk NEI AREDS retinopathy.

Pre-assignment details

No enrolled participant was excluded before assignment to groups. Patients were asked to continue with their normal diet and were asked not to take any dietary supplement containing lutein (or zeaxanthin) beyond the 250 ug (1/4mg) commonly found in pabulum Centrum® type vitamins.

Participants by arm

Arm	Count
Lutein Lutein 9 mg per day	10
Lutein Zeaxanthin 3R 3'R Zeaxanthin 8 mg, Lutein 8 mg per day during 12 months	25
Zeaxanthin 3R 3'R Zeaxanthin 8 mg per day during 12 months	25
Total	60

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Death	1	1	0
Overall Study	Withdrawal by Subject	0	3	4

Baseline characteristics

Characteristic	Lutein	Lutein Zeaxanthin	Zeaxanthin	Total
100% Kinetic Field	5514 Units on a scale (0 to 6000) STANDARD_DEVIATION 2074	1717 Units on a scale (0 to 6000) STANDARD_DEVIATION 765	2649 Units on a scale (0 to 6000) STANDARD_DEVIATION 750	2738 Units on a scale (0 to 6000) STANDARD_DEVIATION 4471
6.5 degrees Tritan threshold	4.9 (dB) STANDARD_DEVIATION 4	8.6 (dB) STANDARD_DEVIATION 12	6 (dB) STANDARD_DEVIATION 9	6.9 (dB) STANDARD_DEVIATION 10
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	7 Participants	20 Participants	21 Participants	48 Participants
Age, Categorical Between 18 and 65 years	3 Participants	5 Participants	4 Participants	12 Participants
Age Continuous	73.9 years STANDARD_DEVIATION 9	75.8 years STANDARD_DEVIATION 9	74.4 years STANDARD_DEVIATION 11	74.9 years STANDARD_DEVIATION 10
Contrast Sensitivity Function Photopic Distance	212 units on a scale STANDARD_DEVIATION 34	204 units on a scale STANDARD_DEVIATION 30	201 units on a scale STANDARD_DEVIATION 22	204 units on a scale STANDARD_DEVIATION 125
Early Treatment Diabetic Retinopathy Study distance visual acuity	93.3 units on a scale STANDARD_DEVIATION 8	86.8 units on a scale STANDARD_DEVIATION 12	88.3 units on a scale STANDARD_DEVIATION 10	88.7 units on a scale STANDARD_DEVIATION 13
Glare Recovery	52.9 Seconds STANDARD_DEVIATION 16	35.6 Seconds STANDARD_DEVIATION 6	26.7 Seconds STANDARD_DEVIATION 5	34.1 Seconds STANDARD_DEVIATION 30
Macular Pigment Optical Density	0.37 Density units of macular pigment STANDARD_DEVIATION 0.05	0.29 Density units of macular pigment STANDARD_DEVIATION 0.06	0.35 Density units of macular pigment STANDARD_DEVIATION 0.04	0.33 Density units of macular pigment STANDARD_DEVIATION 0.05
Sex: Female, Male Female	1 Participants	1 Participants	1 Participants	3 Participants
Sex: Female, Male Male	9 Participants	24 Participants	24 Participants	57 Participants
Shape Discrimination	0.7 % modulation STANDARD_DEVIATION 0.2	0.7 % modulation STANDARD_DEVIATION 0.1	1 % modulation STANDARD_DEVIATION 0.2	0.8 % modulation STANDARD_DEVIATION 0.8

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	0 / 10	0 / 25	0 / 25
serious Total, serious adverse events	0 / 10	0 / 25	0 / 25

Outcome results

Primary

Macular Pigment Optical Density

Replicate measures of foveal 1 degree estimated central MPOD were evaluated with the Quantify® MPS 9000 macular pigment screener, a modified heterochromic flicker photometer (HFP). It employs alternating blue and green flickering LED's and fixation on a 1 degree target, so that a representative measurement at 0.5 degree off center from the fovea is calculated. The method has good repeatability (r = 0.97) and the data are comparable with an objective optical method based on retinal reflectometry (r = 0.78).

Time frame: 4 months

Population: All participants in all arms were tested

Arm	Measure	Value (MEAN)	Dispersion
Lutein	Macular Pigment Optical Density	0.48 Density units of Macular Pigment (du)	Standard Error 0.05
Lutein Zeaxanthin	Macular Pigment Optical Density	0.38 Density units of Macular Pigment (du)	Standard Error 0.06
Zeaxanthin	Macular Pigment Optical Density	0.42 Density units of Macular Pigment (du)	Standard Error 0.04

Primary

Macular Pigment Optical Density

Time frame: 8 months

Population: All participants in all arms were tested

Arm	Measure	Value (MEAN)	Dispersion
Lutein	Macular Pigment Optical Density	0.48 Density units of Macular Pigment (du)	Standard Error 0.05
Lutein Zeaxanthin	Macular Pigment Optical Density	0.44 Density units of Macular Pigment (du)	Standard Error 0.06
Zeaxanthin	Macular Pigment Optical Density	0.46 Density units of Macular Pigment (du)	Standard Error 0.04

Primary

Macular Pigment Optical Density

Replicate measures of foveal 1 degree estimated central MPOD were evaluated with the Quantify® MPS 9000 macular pigment screener, a modified heterochromic flicker photometer (HFP). It employs alternating blue and green flickering light emitting diodes and fixation on a 1 degree target, so that a representative measurement at 0.5 degree off center from the fovea is calculated.

Time frame: 12 months

Population: All participants in all arms were tested

Arm	Measure	Value (MEAN)	Dispersion
Lutein	Macular Pigment Optical Density	0.54 Density units of Macular Pigment (du)	Standard Error 0.05
Lutein Zeaxanthin	Macular Pigment Optical Density	0.52 Density units of Macular Pigment (du)	Standard Error 0.06
Zeaxanthin	Macular Pigment Optical Density	0.48 Density units of Macular Pigment (du)	Standard Error 0.04

Secondary

100% Kinetic Field

Scotomas within the central 20 degree central macula visual field sensitivity was assessed at 5 contrast levels (20, 40, 60, 80, and full contrast). A yellow wavelength stimulus avoided confounding by the lens. Subjects outlined the boundaries of their scotoma(s) on an area-integrating and recording touch flat- screen RGB monitor displaying a central fixation point and movable horizontal/vertical raster lines. The computer calculated summed area of the scotoma(s) with arbitrary scaling from 6000 (dense scotoma) to 0 relative units (absence of scotoma).

Time frame: 12 Months