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Trial registered on ANZCTR

Registration number

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]

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

Condition category

Condition code

Eye

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]

Prevention

Comparator / control treatment

Placebo with an identical appearance.

Control group

Placebo

Outcomes

Primary outcome [1]

Progression of high risk early AMD to late AMD.

Timepoint [1]

Evaluation of AMD status every 6 months.

Secondary outcome [1]

Dynamics of Visual Functions: Colour sensitivity, Flicker sensitivity, Bleach recovery, Kinetics of Dark adaptation.

Timepoint [1]

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

Sex

Both males and females

Can healthy volunteers participate?

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

5/01/2003

Actual

6/04/2003

Date of last participant enrolment

Anticipated

Actual

9/03/2007

Date of last data collection

Anticipated

Actual

Sample size

Target

300

Accrual to date

Final

114

Recruitment in Australia

Recruitment state(s)

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Ian Potter Foundation

Address [1]

Level 3, 111 Collins Street, Melbourne VIC 3000

Country [1]

Australia

Funding source category [2]

Other

Name [2]

Centre for Eye Research Australia

Address [2]

CERA, 32Gisborne Street, East Melbourne, 3002

Country [2]

Australia

Funding source category [3]

Hospital

Name [3]

Royal Victorian Eye and Ear Hospital

Address [3]

RVEEH, 32 Gisborne Street, East Melbourne, VIC, 3002

Country [3]

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]

Hospital

Name [1]

Royal Victorian Eye and Ear Hospital

Address [1]

RVEEH, 32 Gisborne Street, East Melbourne, VIC, 3002

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Royal Victorian Eye and Ear Hospital Research and Ethics Committee

Ethics committee address [1]

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

23/11/2001

Ethics approval number [1]

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

Prof Robyn Guymer

Address

Centre for Eye Research Australia University of Melbourne 32 Gisborne Street East Melbourne VIC 3002

Country

Australia

Phone

+61 3 9929 8360

Fax

[email protected]

Contact person for public queries

Name

Robyn Guymer

Address

Centre for Eye Research Australia
University of Melbourne
32 Gisborne Street
East Melbourne VIC 3002

Country

Australia

Phone

+61 3 99298360

Fax

+61 3 96623859

[email protected]

Contact person for scientific queries

Name

Robyn Guymer

Address

Centre for Eye Research Australia
University of Melbourne
32 Gisborne Street
East Melbourne VIC 3002

Country

Australia

Phone

+61 3 99298360

Fax

+61 3 96623859

[email protected]

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

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