Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
7380
Study information
Scientific title
Genotype and response to treatment for age related macular degeneration (ARMD): a multicentre, non-randomised, interventional, cohort study
Acronym
Study hypothesis
There has been a major advance in our understanding of the genetic and environmental causes of age related macular degeneration (ARMD). Research has implicated smoking and genetic variants in the complement factor pathway and the HTRA1, vascular endothelial growth factor (VEGF) and a number of other genes of lesser effect, in susceptibility to ARMD.
There has also been a parallel advance in the ability to treat this common, blinding disorder using anti-VEGF based treatments, and in particular the VEGF antibody ranibizumab (Lucentis®). This proposal aims to test the hypothesis that response to intravitreal ranibizumab injections in ARMD is, at least in part, modulated by genotype. If genotype does predict response, alternative treatments could be used in those found to benefit least, increasing success rates, saving sight and reducing the need for unnecessary intravitreal injections.
Ethics approval
Leeds East Research Ethics Committee approved in February 2009 (ref: 08/H1306/123)
Study design
Multicentre non-randomised interventional prevention and treatment trial
Primary study design
Interventional
Secondary study design
Non randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Topic: Eye; Subtopic: Eye (all Subtopics); Disease: Ophthalmology
Intervention
This study aims to determine whether genotypes for single nucleotide polymorphisms (SNPs) in the complement factor H, HTRA1 and VEGF genes can predict response to treatment with ranibizumab in patients with ARMD.
The visual acuity change from baseline, in ETDRS letters, will be collected from patients who have completed 6 months of treatment for neovascular AMD with intra-vitreal ranibizumab therapy, given in accordance with the EMEA marketing authorisation. DNA will be collected from study particpants and genotyped for SNPs inthe following genes: HTRA1, VEGF and CFH. The data will be analysed to determine if there is evidence of an association between genotype and treatment outcome.
Follow-up length: 6 months
Study entry: registration only
Intervention type
Other
Phase
Phase IV
Drug names
Primary outcome measure
Association of visual acuity letter score change after 6 months of treatment with intra-vitreal ranibizumab and CFH, HTRA1 and VEGF genotype.
Secondary outcome measures
1. Association of visual acuity letter score change after 6 months of treatment with intra-vitreal ranibizumab and baseline visual acuity
2. Smoking history
3. Sex
4. Lesion type
5. Number of injections
6. Prior treatment status
Overall trial start date
31/03/2009
Overall trial end date
01/03/2011
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Aged over 65 years, either sex
2. Affected with ARM
3. Currently under treatment with ranibizumab (Lucentis)
4. Patients with lesions of greatest linear diameter less than 5400 microns
Participant type
Patient
Age group
Senior
Gender
Both
Target number of participants
Planned sample size: 350; UK sample size: 350
Participant exclusion criteria
1. Patients with poor general health
2. Patients with other eye pathology likely to affect response to treatment
3. Patients with lesions of greatest linear diameter greater than 5400 microns
4. Patients currently being treated with other anti-VEGF agents (systemic or ocular)
Recruitment start date
31/03/2009
Recruitment end date
01/03/2011
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Leeds Teaching Hospitals NHS Trust
Leeds
LS9 7TF
United Kingdom
Sponsor information
Organisation
Leeds Teaching Hospitals NHS Trust (UK)
Sponsor details
Trust Headquarters
St James University Hospital
Beckett Street
Leeds
LS9 7TF
United Kingdom
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Research organisation
Funder name
National Eye Research Centre (NERC) (UK)
Alternative name(s)
NERC
Funding Body Type
private sector organisation
Funding Body Subtype
Universities (academic only)
Location
United Kingdom
Funder name
Novartis Pharmaceuticals UK Ltd (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
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
Basic results (scientific)
Publication list
2012 results in: http://www.ncbi.nlm.nih.gov/pubmed/21558292
Publication citations
-
Results
McKibbin M, Ali M, Bansal S, Baxter PD, West K, Williams G, Cassidy F, Inglehearn CF, CFH, VEGF and HTRA1 promoter genotype may influence the response to intravitreal ranibizumab therapy for neovascular age-related macular degeneration., Br J Ophthalmol, 2012, 96, 2, 208-212, doi: 10.1136/bjo.2010.193680.