The Zeaxanthin and Visual Function Study (ZVF)

• ClinicalTrials.gov Identifier: NCT00564902
• Recruitment Status: Completed
• First Posted: November 29, 2007
• Results First Posted: March 29, 2012
• Last Update Posted: March 29, 2012
• Sponsor: Chrysantis, Inc.
• Collaborators: Kowa Company, Ltd.; IMAGE TECHNOLOGIES INC.
• Information provided by (Responsible Party): Chrysantis, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Age Related Macular Degeneration; Cognition Disorders	Drug: 3R 3'R Zeaxanthin; Dietary Supplement: Lutein; Dietary Supplement: Lutein and Zeaxanthin	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Supportive Care
• Official Title: Randomized, Double Blind, Lutein Controlled Study of Zeaxanthin and Visual Function in Atrophic Age Related Macular Degeneration Patients
• Study Start Date: November 2007
• Actual Primary Completion Date: May 2009
• Actual Study Completion Date: June 2009

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Lutein; 9 mg of Lutein for 12 months	Dietary Supplement: Lutein; 9 mg of Lutein during 12 months
Active Comparator: Zeaxanthin and Lutein; 3R 3'R Zeaxanthin 8 mg, Lutein 8 mg per day during 12 months	Dietary Supplement: Lutein and Zeaxanthin; 8 mg of lutein and 8 mg of Zeaxanthin administered during 12 months
Active Comparator: Zeaxanthin; 3R 3'R Zeaxanthin 8 mg per day during 12 months	Drug: 3R 3'R Zeaxanthin; 8 mg per day during 12 months; Other Name: EZEyes

Outcome Measures

Primary Outcome Measures :

1. Macular Pigment Optical Density [ Time Frame: 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).
2. Macular Pigment Optical Density [ Time Frame: 8 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).
3. Macular Pigment Optical Density [ Time Frame: 12 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 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.

Secondary Outcome Measures :

1. SHAPE Discrimination [ Time Frame: 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.
2. Early Treatment Diabetic Retinopathy Study Distance Visual Acuity [ Time Frame: 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.
3. Glare Recovery [ Time Frame: 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).
4. Contrast Sensitivity Function Photopic Distance [ Time Frame: 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.
5. 6.5 Degrees Tritan Threshold [ Time Frame: 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.
6. 100% Kinetic Field [ Time Frame: 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).

Eligibility Criteria

• Ages Eligible for Study: 45 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Illinois

North Chicago VA Medical Center

North Chicago, Illinois, United States, 60064

Sponsors and Collaborators

Chrysantis, Inc.

Kowa Company, Ltd.

IMAGE TECHNOLOGIES INC.

Investigators

• Principal Investigator: Stuart Richer, Ph. D.; North Chicago VA Medical Center
• Study Director: William Stiles, M.D.; North Chicago VA Medical Center

More Information

Publications:

Delcourt C, Carrière I, Delage M, Barberger-Gateau P, Schalch W; POLA Study Group. Plasma lutein and zeaxanthin and other carotenoids as modifiable risk factors for age-related maculopathy and cataract: the POLA Study. Invest Ophthalmol Vis Sci. 2006 Jun;47(6):2329-35.

Schalch W, Cohn W, Barker FM, Köpcke W, Mellerio J, Bird AC, Robson AG, Fitzke FF, van Kuijk FJ. Xanthophyll accumulation in the human retina during supplementation with lutein or zeaxanthin - the LUXEA (LUtein Xanthophyll Eye Accumulation) study. Arch Biochem Biophys. 2007 Feb 15;458(2):128-35. Epub 2006 Nov 7.

Richer S, Stiles W, Statkute L, Pulido J, Frankowski J, Rudy D, Pei K, Tsipursky M, Nyland J. Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age-related macular degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial). Optometry. 2004 Apr;75(4):216-30.

Richer S, Devenport J, Lang JC. LAST II: Differential temporal responses of macular pigment optical density in patients with atrophic age-related macular degeneration to dietary supplementation with xanthophylls. Optometry. 2007 May;78(5):213-9.

Leung IY, Sandstrom MM, Zucker CL, Neuringer M, Max Snodderly D. Nutritional manipulation of primate retinas. IV. Effects of n--3 fatty acids, lutein, and zeaxanthin on S-cones and rods in the foveal region. Exp Eye Res. 2005 Nov;81(5):513-29.

Neuringer M, Sandstrom MM, Johnson EJ, Snodderly DM. Nutritional manipulation of primate retinas, I: effects of lutein or zeaxanthin supplements on serum and macular pigment in xanthophyll-free rhesus monkeys. Invest Ophthalmol Vis Sci. 2004 Sep;45(9):3234-43.

Akbaraly NT, Faure H, Gourlet V, Favier A, Berr C. Plasma carotenoid levels and cognitive performance in an elderly population: results of the EVA Study. J Gerontol A Biol Sci Med Sci. 2007 Mar;62(3):308-16.

Thomson LR, Toyoda Y, Langner A, Delori FC, Garnett KM, Craft N, Nichols CR, Cheng KM, Dorey CK. Elevated retinal zeaxanthin and prevention of light-induced photoreceptor cell death in quail. Invest Ophthalmol Vis Sci. 2002 Nov;43(11):3538-49.

• Responsible Party: Chrysantis, Inc.
• ClinicalTrials.gov Identifier: NCT00564902
• Other Study ID Numbers: CHRY1; IRB 07-046 ( Other Identifier: Edward Hines Jr. VA Hospital/North Chicago VAMC )
• First Posted: November 29, 2007
• Results First Posted: March 29, 2012
• Last Update Posted: March 29, 2012
• Last Verified: March 2012

Keywords provided by Chrysantis, Inc.:

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

Additional relevant MeSH terms:

Macular Degeneration; Cognition Disorders; Retinal Degeneration; Retinal Diseases; Eye Diseases; Neurocognitive Disorders; Mental Disorders