Effect of Carotenoids Supplementation on Visual Function in Chinese Subjects

Study Overview
=================
Brief Summary
-----------------
The macula is a pigmented area at the center of the retina, and responsible for the central, high-resolution color vision. Age-related macular degeneration (AMD) is a disease of the macula and is the leading cause of irreversible vision impairment and blindness worldwide. The yellow pigment at the macula is referred to as macular pigment. There is now strong evidence showing that macular pigment (MP), which is composed of the dietary carotenoids lutein (L), meso-zeaxanthin (MZ), and zeaxanthin (Z) is protective against AMD and vision loss. MP is a powerful antioxidant and also filters short-wavelength (blue) light at the macula. The AREDS2 study concluded that supplementation of L and Z is beneficial for patients with non-advanced age-related macular degeneration (AMD). The CREST and other studies had reported that dietary supplementation of these carotenoids could enhance contrast sensitivity among the Caucasian population, whereas little information is known about the effect of dietary supplementation of carotenoids on contrast sensitivity among Chinese. Thus in this study, we aim to investigate whether supplementation of a formulation containing 10 mg L, 10 mg MZ, and 2mg Z on contrast sensitivity in Chinese subjects free of retinal disease. This study is a single-center, double-blinded, placebo-controlled, randomized clinical trial conducted at Zhongshan Ophthalmic Center (ZOC), Sun Yat-sen University, Guangzhou, China. Participants in the intervention group received oral supplementation of 10 mg L, 10 mg MZ, and 2mg Z in a formula base oil suspension as one soft gel capsule in the morning per day. Participants in the control group receive one soft gel capsule of placebo oil per day. The intervention and placebo supplements are identical in external appearance, and the two treatments are therefore indistinguishable from each other. The duration of the study intervention is 12 months, and study visits are conducted at baseline, 3 months, 6 months, and 12 months. The primary outcome measure is the change in contrast sensitivity (CS) at 6 cycles per degree (cpd) over the study course: Y=CS4-CS1, where CS1 is CS at 6 cpd at baseline, CS4 is the CS at 6cpd at the 12-month follow-up. The secondary outcomes of this study include CS at other cpds and at other study visits, best-corrected visual acuity, subjective visual function, and skin carotenoid levels at each study visit.

Official Title
-----------------
Effect of Carotenoids Supplementation on Visual Function in Chinese Subjects Free of Retinal Disease: A Randomized Clinical Trial

Conditions
-----------------
Vision Disorders

Intervention / Treatment
-----------------
* Dietary Supplement: Carotenoids supplementation
* Dietary Supplement: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Chinese subjects Age 35 years or above Monocular BCVA of 6/6 or better No more than +/- 5 diopters spherical equivalence of refraction No previous consumption of supplements containing macular carotenoids (L, Z and/or MZ) within the last 12 months Without severe retinal diseases (eg. retinal detachment, glaucoma, macular hole, idiopathic epiretinal membrane, retinitis pigmentosa, and age-related macular degeneration (assessed by experienced ophthalmologists during ocular examination) Exclusion Criteria: Unable to provide informed consent With diagnosed diabetes With severe systemic disease which affects physical mobility and successful follow-up Contrast sensitivity at a spatial density of 6 cpd ≤ 1.5 % at baseline in the eye with better visual acuity Subjects who plan to receive cataract surgery within the next year Subjects who are unable to cooperate with the examinations during follow-ups, such as those who suffer from other serious systemic diseases or mental abnormalities History of intraocular surgery (eg. cataract surgery, vitrectomy and retinal laser photocoagulation)

Ages Eligible for Study
-----------------
Minimum Age: 35 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Carotenoids group<br>Participants in the intervention group receive oral supplementation of 10 mg L, 10 mg MZ and 2mg Z in a formula base oil suspension as one soft gel capsule in the morning per day. Each capsule contains 22 mg of carotenoids (10+10+2mg), thus each participant in the intervention group will receive a total of 22 mg of carotenoids per day. | Dietary Supplement: Carotenoids supplementation<br>* Daily oral supplementation of a soft gel capsule containing 10mg lutein (L), 10mg meso-zeaxanthin (MZ) and 2mg zeaxanthin (Z).<br>|
| Placebo Comparator: Placebo group<br>Participants in the control group receive one soft gel capsule of placebo oil per day. | Dietary Supplement: Placebo<br>* Daily oral supplementation of a soft gel capsule containing only placebo oil<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in contrast sensitivity (CS) at 6 cycles per degree (cpd) over 1 year | CS at 6 cpd at the 12-month follow-up minus CS at 6 cpd at baseline. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CS at other cpds and at other study visits | CS at 1.2, 2.4, 9.6 and 15.15 cpd at baseline, 3-month follow-up, 6-month follow-up and 12-month follow-up; as well as CS at 6 cpd at 3-month follow-up and 6-month follow-up | 1 year | 
| Best-corrected visual acuity | Best-corrected visual acuity at baseline, 3-month follow-up, 6-month follow-up and 12-month follow-up | 1 year | 
| Subjective visual function | Subjective visual function measured by questionnaire at baseline, 3-month follow-up, 6-month follow-up and 12-month follow-up | 1 year | 
| Skin carotenoids score | Skin carotenoids score at baseline, 3-month follow-up, 6-month follow-up and 12-month follow-up | 1 year |