Condition category
Eye Diseases
Date applied
28/05/2010
Date assigned
28/05/2010
Last edited
29/08/2013
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Mr Martin McKibbin

ORCID ID

Contact details

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

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 (LucentisĀ®). 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 measures

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

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

http://www.leedsteachinghospitals.com/

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

academic

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

Results - basic reporting

Publication summary

2012 results in: http://www.ncbi.nlm.nih.gov/pubmed/21558292

Publication citations

  1. 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.

Additional files

Editorial Notes