Intraocular Cytokines in Non-responders to Ranibizumab Treatment for Neovascular AMD

October 9, 2018 updated by: Wai-Ching Lam, University Health Network, Toronto

Neovascular Age-related Macular Degeneration: Intraocular Inflammatory Cytokines in the Non-responder to Ranibizumab Treatment

The purpose of this study is to evaluate the level of cytokines (which are small proteins important in cell signalling) in eye fluid (aqueous humour) in patients with wet age related macular degeneration patients who have been treated with an injection in the eye (intravitreal injection) with a drug called ranibizumab. The level of cytokines will be compared between patients who have a good response to ranibizumab treatment and patients who are non-responsive to ranibizumab and need other forms of therapy. This knowledge will help for the future treatment and to potentially develop new medication for wet age-related macular degeneration.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

In the treatment of CNV (Choroidal NeoVascularization) secondary from AMD (Age Related Macular Degeneration) by using ranibizumab, patients who are non-responders can be found in approximately 1-10% of treatments. Thus, failure of treatment can lead to loss of vision. Growth factors and cytokines, such as vascular endothelial growth factor (VEGF), pigment epithelium derived factor (PEDF), interleukin 6 (IL-6) and placenta growth factor (PLGF) are known to play an important role in the development of CNV angiogenesis.

The rationale for conducting this study to compare VEGF, PEDF, IL-6 and PLGF cytokine levels in the aqueous humor of wet AMD and Polypoidal Choroidal Vasculopathy (PCV) patients who are poor responders to anti VEGF treatment and age-matched "good" responders to anti VEGF. Ranibizumab poor responders in AMD and PCV, who are treated with a combination of PDT/ranibizumab or intravitreous injection of aflibercept (Eyelea®, Regeneron Pharmaceuticals Inc. Tarrytown, NY, USA and Bayer, Basel, Switzerland) will be enrolled to the study. An aqueous humor sample will be obtained when patient receives intravitreal injection treatment and also at 1, 2 months follow up period. VEGF, PEDF,IL-6 and PLGF in aqueous will be analyzed and used to compare between the poor response group and age matched patient with good response to ranibizumab. Age, gender, visual acuity, central macular thickness by OCT, lesion size and fundus autofluorescence data will be collected and used to compare between these groups. Subgroup analysis of different treatment comparison with ranibizumab good responder group will be evaluated. Factors associated with the non-responders of ranibizumab will be analyzed.

Non-responders to ranibizumab treatment in AMD may have different levels and responses of inflammatory cytokines compared to the responder group. Understanding the pathogenesis and characteristic of this specific group of patients can help narrow down a specific choice of treatment and prevent the reduction of visual acuity of the patient. This study also helps identify factors associated to poor responders from ranibizumab treatment for wAMD.

Study Type

Observational

Enrollment (Actual)

30

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M2N4H3
        • Toronto Western Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Study patients in the treatment group will be those greater than 50 years old, with age related macular degeneration, who are non-responder/ resistance to ranibizumab treatment. Control group will include patients who are responders to ranibizumab treatment.

Description

Inclusion Criteria:

  • Age 50 years or more
  • Ranibizumab resistance/poor responder patients in all AMD entities (typical AMD, PCV and RAP) who will be treated with intravitreous ranibizumab in combination with verteporfin photodynamic therapy
  • Ranibizumab resistance/poor responder patients in all AMD entity (typical AMD, PCV and RAP) who will be treated with intravitreous aflibercept injection
  • AMD patient who is good response to the treatment of ranibizumab (control group)

Exclusion Criteria:

  • Any evidence of good response in treatment of ranibizumab,
  • Uncooperative patients to intravitreal treatment
  • Patients who have clinically active ocular inflammation
  • Patients who have previous PDT treatment within 6 months
  • Patient who previously have ocular treatment of immunosuppressive agent within 3 months
  • Patient who previously have ocular treatment of steroid with in 3 months
  • Patients who are currently on systemic treatment of anti-VEGF medication or immunosuppressive agents.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Non-responders receiving aflibercept therapy
Non-responders to ranibizumab who are now receiving aflibercept therapy
Drug: Aflibercept
anti-VEGF treatment for wet age related macular degeneration
Other Names:
  • Eylea (R)
Non-responders receiving PDT combo therapy
patients who are non-responders to ranibizumab who have been switched to combination photodynamic therapy (PDT)
Procedure: Combination Photodynamic Therapy
Use of cold laser with an intravitreal injection of dexamethasone to treat wet age related macular degeneration
Responders to ranibizumab
Patients who are responders to ranibizumab and are continuing monthly injections.
Drug: Ranibizumab
anti-VEGF treatment for wet age related macular degeneration
Other Names:
  • Lucentis

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Aqueous Humour Cytokine Levels
Time Frame: At time of Intravitreal Injection
At time of Intravitreal Injection

Secondary Outcome Measures

Outcome Measure
Time Frame
Demographic Data
Time Frame: At time of appointment
At time of appointment
Number of anti-VEGF injections before developing non-responder characteristics
Time Frame: At time of appointment
At time of appointment
History of Previous Treatment
Time Frame: At time of appointment
At time of appointment
Optical Coherence Tomography (OCT) results
Time Frame: At time of appointment
At time of appointment
Fluorescein Angiography Results and Indocyanine Green Angiography Results
Time Frame: At time of appointment
At time of appointment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Health Network, Toronto

Investigators

  • Principal Investigator: Wai-Ching Lam, MD, Toronto Western Hospital, University Health Network, University of Toronto

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2014

Primary Completion (Actual)

August 1, 2016

Study Completion (Actual)

December 1, 2016

Study Registration Dates

First Submitted

August 13, 2014

First Submitted That Met QC Criteria

August 13, 2014

First Posted (Estimate)

August 18, 2014

Study Record Updates

Last Update Posted (Actual)

October 11, 2018

Last Update Submitted That Met QC Criteria

October 9, 2018

Last Verified

October 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VEGF wAMD cytokine study

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Age Related Macular Degeneration

Clinical Trials on Aflibercept

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Russia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe