The putative beneficial effects of supplemental Lutein (L) and Zeaxanthin (Z) with co-antioxidants in patients with age-related maculopathy: A pilot short term randomised controlled clinical trial of antioxidant supplementation

ISRCTN	ISRCTN94557601
DOI	https://doi.org/10.1186/ISRCTN94557601
Protocol serial number	DMP628.1.03
Sponsor	Dr. Mann Pharma GmbH, Bausch & Lomb Group (Germany)
Funder	Dr Mann Pharma, Bausch and Lomb and Chauvin Group Berlin, Germany

Submission date: 01/07/2005
Registration date: 25/07/2005
Last edited: 12/12/2012

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Eye Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Usha Chakravarthy
Scientific

Ophthalmology and Vision Science
Institute of Clinical Science
Queen's Univerisity of Belfast
Royal Victoria Hospital
Belfast
BT12 6BA
United Kingdom

Phone	+44 (0)28 90633955
Email	u.chakravarthy@qub.ac.uk

Study information

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
Scientific title
Study acronym	CARMA
Study objectives	Subjects aged 50 years and older with evidence of early ARM in both eyes or advanced AMD in one eye. The primary hypothesis is that progression from early ARM to late AMD may be delayed or prevented through supplementation with key antioxidants (vitamins, minerals and carotenoids) which are either known to be present in high concentrations in healthy neural retina/retinal pigment epithelium (RPE)/choroidal interface or are free radical scavengers and thus have potential protective roles in minimisation of oxidative stress.
Ethics approval(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	Age-related maculopathy
Intervention	Daily oral administration of supplement - Lutein + Zeaxanthin + Vitamin E + C + Zn/Cu tablet per day (to be known as CARMA Preparation) Control: Placebo
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Lutein, Zeaxanthin, co-antioxidants
Primary outcome measure(s)	The primary outcome will be retinal acuity in the study eye at 12 months of supplementation. The level of significance for changes will be set at 0.05.
Key secondary outcome measure(s)	1. Change in distance visual acuity (DVA) in treatment and control groups at 12 months. Similar to the primary outcome the level of significance for changes will be set at 0.05. 2. Progression of ARM based on detailed grading of stereo colour fundus images. Progression is defined as a change of at least one step in the level of severity as gauged by the appearance or an increase in (a) drusen (size, frequency and extent), (b) focal hyper or hypopigmentation (area). 3. In vivo macular carotenoid signal strength. 4. Serum markers Vitamin C, lipid soluble vitamins, cholesterol. Data from all patients who continued supplementation for more than 12 months will be collected and analysed in order get as much information as possible regarding the changes of visual function during the duration of the study. These additional data will be analysed independently from the primary and secondary outcomes at 12 months of supplementation.
Completion date	01/04/2007

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	360
Key inclusion criteria	1. Patient must be willing to give written informed consent, make the required study visits, and follow instructions 2. Patient must be at least 50 years of age 3. Patients may be of any race or sex 4. Two groups of ARM patients may be included Group 1: If there is choroidal neovascularisation (CNV) or geographic atrophy (GA) in one eye, any level of ARM is permissible in the fellow eye provided visual acuity (VA) is equal to or better than logarithm of the minimum angle of resolution (logMAR) 0.3 Group 2: Clinical diagnosis of severe early ARM in at least one eye. ≥20 soft distinct or soft indistinct drusen or if fewer that 20 soft drusen, focal hyper pigmentation must be present. Visual acuity greater than or equal to 6/12 or 0.3 logMAR in the study eye (which may be both eyes).
Key exclusion criteria	1. Any retinal laser therapy in the study eye 2. In Group 1 there should be no visible choroidal neovascularisation or geographic atrophy 3. History of any unstable medical condition or life threatening conditions, for example, cancer or renal failure, that would preclude scheduled study visits or completion of the study 4. History of ophthalmic disease in the study eye (other than ARM) that would compromise the visual acuity of the study eye 5. Patients currently on supplements containing the antioxidants C, E, Zn, L and Z will be asked to discontinue them and may, after a washout period of three months, be eligible for randomisation into the study 6. History of malabsorption 7. History of psychiatric disorder, which may interfere with compliance in taking study medication or attendance for study visits 8. Patients with known allergy against one of the active ingredients or the other excipients in the study medications
Date of first enrolment	01/06/2004
Date of final enrolment	01/04/2007

Locations

Countries of recruitment

United Kingdom
Northern Ireland

Study participating centre

Ophthalmology and Vision Science

Belfast
BT12 6BA
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Peer reviewed?	Patient-facing?
Results article	results	01/09/2011	Yes	No
Results article	results	01/03/2013	Yes	No
Other publications	design and methods	01/11/2008	Yes	No