Age related macular degeneration pharmacogenetics study

ISRCTN ISRCTN44202629
DOI https://doi.org/10.1186/ISRCTN44202629
Secondary identifying numbers 7380
Submission date
28/05/2010
Registration date
28/05/2010
Last edited
29/08/2013
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

Mr Martin McKibbin
Scientific

Leeds Teaching Hospitals NHS Trust
Department of Opthalmology
St James's University Hospital
Leeds
LS9 7TF
United Kingdom

Study information

Study designMulticentre non-randomised interventional prevention and treatment trial
Primary study designInterventional
Secondary study designNon randomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Scientific titleGenotype and response to treatment for age related macular degeneration (ARMD): a multicentre, non-randomised, interventional, cohort study
Study objectivesThere 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(s)Leeds East Research Ethics Committee approved in February 2009 (ref: 08/H1306/123)
Health condition(s) or problem(s) studiedTopic: Eye; Subtopic: Eye (all Subtopics); Disease: Ophthalmology
InterventionThis 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 typeOther
Primary outcome measureAssociation of visual acuity letter score change after 6 months of treatment with intra-vitreal ranibizumab and CFH, HTRA1 and VEGF genotype.
Secondary outcome measures1. 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 study start date31/03/2009
Completion date01/03/2011

Eligibility

Participant type(s)Patient
Age groupSenior
SexBoth
Target number of participantsPlanned sample size: 350; UK sample size: 350
Key inclusion criteria1. 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
Key exclusion criteria1. 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)
Date of first enrolment31/03/2009
Date of final enrolment01/03/2011

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

Leeds Teaching Hospitals NHS Trust
Leeds
LS9 7TF
United Kingdom

Sponsor information

Leeds Teaching Hospitals NHS Trust (UK)
Hospital/treatment centre

Trust Headquarters
St James University Hospital
Beckett Street
Leeds
LS9 7TF
England
United Kingdom

Website http://www.leedsteachinghospitals.com/
ROR logo "ROR" https://ror.org/00v4dac24

Funders

Funder type

Research organisation

National Eye Research Centre (NERC) (UK)
Private sector organisation / Universities (academic only)
Alternative name(s)
National Eye Research Centre, SightResearchUK, SRUK, NERC
Location
United Kingdom
Novartis Pharmaceuticals UK Ltd (UK)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/02/2012 Yes No
HRA research summary 28/06/2023 No No