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Trial registered on ANZCTR


Trial ID
ACTRN12605000320651
Ethics application status
Approved
Date submitted
1/09/2005
Date registered
6/09/2005
Date last updated
10/11/2015
Type of registration
Retrospectively registered

Titles & IDs
Public title
Age-Related Maculopathy Statin Study
Scientific title
Role Of Cholesterol-lowering Medications ("Statins") In the Progression of Age-Related Macular Degeneration
Secondary ID [1] 139 0
01/451H
Universal Trial Number (UTN)
Trial acronym
ARMSS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Age-related macular degeneration 408 0
Condition category
Condition code
Eye 479 479 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Two tablets of simvastatin, 20 mg each, daily. The planned duration of the intervention/control is five years.
Intervention code [1] 324 0
Prevention
Comparator / control treatment
Placebo with an identical appearance.
Control group
Placebo

Outcomes
Primary outcome [1] 549 0
Progression of high risk early AMD to late AMD.
Timepoint [1] 549 0
Evaluation of AMD status every 6 months.
Secondary outcome [1] 1167 0
Dynamics of Visual Functions: Colour sensitivity, Flicker sensitivity, Bleach recovery, Kinetics of Dark adaptation.
Timepoint [1] 1167 0
Evaluation of visual functions every 6 months.

Eligibility
Key inclusion criteria
(1) The ability to assess the macula in at least one eye, (2) VA better than or equal to 6/18 in the study eye(s). (3) High risk drusen in both eyes: one or more large soft druse (125 microns), or >10 intermediate drusen (62.5 microns) ORLate AMD (CNV, GA) in one eye and any drusen or pigment change in the study eye.Note: the study eye is allowed to have non-central GA and/or non-neovascular PED (4) cholesterol level within the normal limits according to the person's medical history (5) not currently on any cholesterol-lowering medication.
Minimum age
50 Years
Maximum age
Not stated
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
(1) Medical and ophthalmic conditions which potentially affects visual function, including visually significant cataract (as defined by WILMER's grading method-that is nuclear opacity score of 2.00 or greater, cortical opacity score of greater than 3, any posterior subcapsular cataract), history of diabetes and glaucoma(2) Use of medications which may affect visual function, such as plaquenil, chloroquine, major tranquilizers.(3) cholesterol levels outside the normal limits given person's medical history.(a)Existing coronary heart disease:-- cholesterol > 4 mmol/L(b) Diabetics, people with hypertension, peripheral vascular disease, family history of hypercholesterolaemia or coronary heart disease:-- cholesterol > 6.5mmol/L or cholesterol > 5.5 if HDL <1.0mmol/L(c) people with HDL <1.0mmol/L:--cholesterol >6.5mmol/L(d) men aged 35 to 75 years or postmenopausal women up to 75 years:-- cholesterol >7.5 or triglycerides > 4.0mmol/L(e) people with none of the above:--cholesterol >9.0 or triglycerides >8.0mmol/L(4)Statins is clinically contraindicated:(a) Allergy(b) ALT > 2 times the upper limit of normal(c) Previous severe adverse reactions to statin.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The allocation list is stored at a remote site. The medications are dispensed in identical numbered containers. Study personnel do not have access to the medication code and are not involved in the process of packing of the medications.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation schedule was prepared by a biostatistician using a permuted blocks allocation scheme.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 543 0
Charities/Societies/Foundations
Name [1] 543 0
Ian Potter Foundation
Address [1] 543 0
Level 3, 111 Collins Street, Melbourne VIC 3000
Country [1] 543 0
Australia
Funding source category [2] 544 0
Other
Name [2] 544 0
Centre for Eye Research Australia
Address [2] 544 0
CERA, 32Gisborne Street, East Melbourne, 3002
Country [2] 544 0
Australia
Funding source category [3] 545 0
Hospital
Name [3] 545 0
Royal Victorian Eye and Ear Hospital
Address [3] 545 0
RVEEH, 32 Gisborne Street, East Melbourne, VIC, 3002
Country [3] 545 0
Australia
Primary sponsor type
University
Name
Centre for Eye Research Australia
Address
CERA, 32 Gisborne Street, East Melbourne, VIC, 3002
Country
Australia
Secondary sponsor category [1] 439 0
Hospital
Name [1] 439 0
Royal Victorian Eye and Ear Hospital
Address [1] 439 0
RVEEH, 32 Gisborne Street, East Melbourne, VIC, 3002
Country [1] 439 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 1548 0
Royal Victorian Eye and Ear Hospital Research and Ethics Committee
Ethics committee address [1] 1548 0
Ethics committee country [1] 1548 0
Australia
Date submitted for ethics approval [1] 1548 0
Approval date [1] 1548 0
23/11/2001
Ethics approval number [1] 1548 0

Summary
Brief summary
BACKGROUND: HMG Co-A reductase inhibitors are ubiquitous in our community yet their potential role in age-related macular degeneration (AMD) remains to be determined.

METHODOLOGY/PRINCIPAL FINDINGS:
OBJECTIVES: To evaluate the effect of simvastatin on AMD progression and the effect modification by polymorphism in apolipoprotein E (ApoE) and complement factor H (CFH) genes.

DESIGN: A proof of concept double-masked randomized controlled study.

PARTICIPANTS: 114 participants aged 53 to 91 years, with either bilateral intermediate AMD or unilateral non-advanced AMD (with advanced AMD in fellow eye), BCVA = 20/60 in at least one eye, and a normal lipid profile.

INTERVENTION: Simvastatin 40 mg/day or placebo, allocated 1:1.

MAIN OUTCOME MEASURES: Progression of AMD either to advanced AMD or in severity of non-advanced AMD. Results. The cumulative AMD progression rates were 70% in the placebo and 54% in the simvastatin group. Intent to treat multivariable logistic regression analysis, adjusted for age, sex, smoking and baseline AMD severity, showed a significant 2-fold decrease in the risk of progression in the simvastatin group: OR 0.43 (0.18-0.99), p = 0.047. Post-hoc analysis stratified by baseline AMD severity showed no benefit from treatment in those who had advanced AMD in the fellow eye before enrolment: OR 0.97 (0.27-3.52), p = 0.96, after adjusting for age, sex and smoking. However, there was a significant reduction in the risk of progression in the bilateral intermediate AMD group compared to placebo [adjusted OR 0.23 (0.07-0.75), p = 0.015]. The most prominent effect was observed amongst those who had the CC (Y402H) at risk genotype of the CFH gene [OR 0.08 (0.02-0.45), p = 0.004]. No evidence of harm from simvastatin intervention was detected.

CONCLUSION/SIGNIFICANCE: Simvastatin may slow progression of non-advanced AMD, especially for those with the at risk CFH genotype CC (Y402H). Further exploration of the potential use of statins for AMD, with emphasis on genetic subgroups, is warranted.
Trial website
Trial related presentations / publications
1. . Proof of concept, randomized, placebo-controlled study of the effect of simvastatin on the course of age-related macular degeneration. Guymer RH, Baird PN, Varsamidis M, Busija L, Dimitrov PN, Aung KZ, Makeyeva GA, Richardson AJ, Lim L, Robman LD.
PLoS One. 2013 Dec 31;8(12):e83759. doi: 10.1371/journal.pone.0083759. eCollection 2013.

2. Effect of simvastatin on retinal vascular caliber: the Age-Related Maculopathy Statin Study. Sasaki M, Gan WL, Kawasaki R, Hodgson L, Lee KY, Wong TY, Lamoureux E, Robman L, Guymer R. Acta Ophthalmol. 2013 Aug;91(5):e418-9. doi: 10.1111/aos.12114. No abstract available.
Public notes

Contacts
Principal investigator
Name 36024 0
Prof Robyn Guymer
Address 36024 0
Centre for Eye Research Australia University of Melbourne 32 Gisborne Street East Melbourne VIC 3002
Country 36024 0
Australia
Phone 36024 0
+61 3 9929 8360
Fax 36024 0
Email 36024 0
rhg@unimelb.edu.au
Contact person for public queries
Name 9513 0
Prof Robyn Guymer
Address 9513 0
Centre for Eye Research Australia
University of Melbourne
32 Gisborne Street
East Melbourne VIC 3002
Country 9513 0
Australia
Phone 9513 0
+61 3 99298360
Fax 9513 0
+61 3 96623859
Email 9513 0
rhg@unimelb.edu.au
Contact person for scientific queries
Name 441 0
Prof Robyn Guymer
Address 441 0
Centre for Eye Research Australia
University of Melbourne
32 Gisborne Street
East Melbourne VIC 3002
Country 441 0
Australia
Phone 441 0
+61 3 99298360
Fax 441 0
+61 3 96623859
Email 441 0
rhg@unimelb.edu.au