Condition category
Eye Diseases
Date applied
17/07/2012
Date assigned
22/08/2012
Last edited
18/06/2014
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
The macula is the central part of the retina at the back of the eye responsible for fine detail, central and colour vision. We believe that a pigment (colour) found at the macula known as macular pigment may help increase visual performance and reduce problems with glare from bright light in people with otherwise normal vision (i.e., no eye disease). This could be important for everybody, and especially those who rely strongly on good vision, like pilots, train drivers and athletes. Macular pigment is made up of three naturally occurring pigments known as carotenoids. These macular carotenoids are lutein, zeaxanthin and meso-zeaxanthin. Research has shown that this dietary pigment may be increased by taking food supplements that contain these three important carotenoids.

Who can participate?
This study is open to any adult aged 18 years or over with no eye disease.

What does the study involve?
The study involves four visits to the Vision Research Centre over a 12-month period. Each study visit will take around two and half hours. Study visits will involve various non-invasive vision tests along with visual performance and experience (assessed by questionnaire). We will also take a blood sample to measure the carotenoid nutrients in blood before and following supplementation. The blood sample will be taken by a trained professional. Functioning of mental processes will also be tested (using computerised tests) at each study visit, as these nutrients are also found in the brain. Study volunteers will be randomly allocated to receive either an eye-related dietary supplement (containing carotenoids) or a placebo (a tablet identical to the supplement but containing no carotenoids or other active ingredients). Neither the study organisers nor the volunteers will know which tablet each person receives. The study volunteers will be provided with a summary of their height, weight, blood pressure and advice (e.g., lifestyle modification for those who are overweight), as appropriate. Information leaflets on lifestyle changes (e.g. advice on healthy eating, regular physical activity and stopping smoking) will be provided at the study centre. In the case of measurements that may require immediate action, for example if the participant’s blood pressure is dangerously high, the participant will be advised to go directly to their GP or local hospital, and any assistance needed to make these arrangements will be provided by an appropriate member of the study team.

What are the possible benefits and risks of participating?
We anticipate that this research will benefit a wide range of people with respect to vision and visual performance. The leaflet used to recruit participants will clearly state that any benefits arising from the research is likely to be in the longer term and to society in general, rather than to them personally. We foresee no risks to the study volunteers. The dietary supplement used in the study has been tested and has been deemed suitable for human consumption. In the unlikely event of a study volunteer experiencing any side effects, a concerned authority will be informed immediately and appropriate protective action for the volunteer will be taken.

Where is the study run from?
The study will be run from the Macular Pigment Research Group’s Vision Research Centre at the Waterford Institute of Technology, Waterford, Ireland.

When is the study starting and how long is it expected to run for?
The study will start in September 2012 and each patient will be enrolled for 12 months. It may take us up to 1 year to recruit all the patients for this study and so the expected finish date could be August 2014.

Who is funding the study?
This study is funded by the European Research Council, Belgium.

Who is the main contact?
Miss Sarah O’Regan
soregan@wit.ie

Trial website

http://www.mprg.ie

Contact information

Type

Scientific

Primary contact

Dr John Nolan

ORCID ID

Contact details

Macular Pigment Research Group
Vision Research Centre
Carriganore House
Waterford Institute of Technology
Carriganore
Waterford
-
Ireland
+353 51 834074
jmnolan@wit.ie

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

281096

Study information

Scientific title

Enrichment of macular pigment with respect to vision in normal subjects

Acronym

CREST Normal

Study hypothesis

The macula, the central part of the retina, is responsible for optimal spatial vision. There is a growing body of evidence that a dietary pigment at the macula, known as macular pigment, can enhance visual performance and experience by filtering short-wavelength (blue) light and thereby reducing the effects of chromatic aberration and light scatter. Chromatic aberration causes out of focus vision and light scatter causes glare disability in all normal individuals. Macular pigment contains the carotenoids lutein, zeaxanthin and meso-zeaxanthin. The typical western diet contains around 60 carotenoids, and 18 have been identified in human serum. However, only three carotenoids are found at the macula, indicating the unique biological selectivity for their uptake at this location. It is likely that the accumulation of macular pigment has evolved because of its optical and antioxidant properties. For example, macular pigment limits retinal oxidative damage passively (through filtration of blue light) and actively (by quenching free radicals). Recent research has shown that macular pigment can be augmented by dietary supplementation in most (but not all) subjects, suggesting that the macular concentrations of these carotenoids are
suboptimal in many people. Our research group has discovered that a dip in the central portion of this pigment, seen in around 12% of individuals, is an undesirable feature of its spatial profile and may be linked to an inability to generate meso-zeaxanthin at the macula. We have also identified that enrichment of macular pigment, including reconstruction of undesirable central dips, can be achieved by inclusion of meso-zeaxanthin in a dietary supplement. We propose to uniquely enrich macular pigment with all three macular carotenoids, and assess its impact on visual performance and experience in normal subjects. This ground-breaking study will advance our understanding of the optical hypothesis of macular pigment, and potentially improve normal vision.

Ethics approval

Research Ethics Committee, Waterford Institute of Technology, Ireland, 02/11/2010, ref: 10/JN/01

Study design

Single-centre double-blind randomised placebo-controlled study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Screening

Patient information sheet

http://www.wit.ie/images/uploads/Research_PDF/CREST_Normal_Patient_information_leaflet.pdf

Condition

Chromatic aberration and light scatter impacting on visual performance

Intervention

Intervention 1: a soft-gel carotenoid combination formulation containing 10 mg meso-zeaxanthin, 10 mg lutein and 2 mg zeaxanthin in a sunflower oil suspension.
Intervention 2: soft-gel placebo control containing sunflower oil.

One tablet to be taken per day, preferably with a meal, for the duration of the study.

Total duration of intervention is 12 months

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

Contrast sensitivity at 12 months of supplementation. The level of significance for changes will be set at 0.05

Secondary outcome measures

All outcome measures will be measured at each study visit (i.e. baseline, 3, 6 and 12 months):
1. Glare disability (measured by the Functional Vision Analyzer)
2. Photostress recovery (measured by threshold contrast sensitivity before and after a 10-second exposure to blue photostress lamp)
3. Macular pigment (measured using customised heterochromatic flicker photometry [Macular Metrics II Maculux] and dual wavelength autofluorescence [Heidelberg Engineering Spectralis])
4. Visual acuity (measured using Snellen letters [Thomson chart])
5. Light scatter (measured using the C-Quant)
6. Foveal architecture (measured using the Heidelberg Engineering Spectralis and the Zeiss Visucam 200)
7. Serum carotenoid concentrations (measured by high performance liquid chromatography analysis)
8. Cognitive function (measured using the Cambridge Cognition CANTAB [CAmbridge Neuropsychological Test Automated Battery] software)

Overall trial start date

01/09/2012

Overall trial end date

31/08/2014

Reason abandoned

Eligibility

Participant inclusion criteria

1. Age 18 years or over
2. Corrected distance visual acuity of ≥ 6/6
3. Spectacle prescription of ≤ ±5D
4. Have not taken eye-related dietary supplements containing the macular carotenoids (lutein, zeaxanthin and/or meso-zeaxanthin) in the previous 12 months
5. No ocular pathology
6. Macular pigment optical density at 0.25 degrees ≤ 0.4

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

60 subjects and 60 controls

Participant exclusion criteria

1. Ocular pathology
2. Recent history of carotenoid supplementation
3. Younger than 18 years old
4. Corrected distance visual acuity of < 6/6
5. Spectacle prescription of > ±5D
6. Macular pigment optical density at 0.25 degrees > 0.4

Recruitment start date

01/09/2012

Recruitment end date

31/08/2014

Locations

Countries of recruitment

Ireland, United Kingdom

Trial participating centre

Macular Pigment Research Group
Waterford
-
Ireland

Sponsor information

Organisation

European Research Council (EU)

Sponsor details

c/o Graeme Horley
Wilton Park House
Wilton Place
Dublin
2
Ireland
+353 1 607 3118
graeme.horley@sfi.ie

Sponsor type

Research council

Website

http://erc.europa.eu/

Funders

Funder type

Government

Funder name

European Research Council (EU) ref: 281096

Alternative name(s)

ERC

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

Belgium

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2014 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/24621122

Publication citations

  1. Protocol

    Akuffo KO, Beatty S, Stack J, Dennison J, O'Regan S, Meagher KA, Peto T, Nolan J, Central Retinal Enrichment Supplementation Trials (CREST): design and methodology of the CREST randomized controlled trials., Ophthalmic Epidemiol, 2014, 21, 2, 111-123, doi: 10.3109/09286586.2014.888085.

Additional files

Editorial Notes