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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02218177
Recruitment Status : Completed
First Posted : August 18, 2014
Last Update Posted : October 11, 2018
Sponsor:
Information provided by (Responsible Party):
Wai-Ching Lam, University Health Network, Toronto

Brief Summary:
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.

Condition or disease Intervention/treatment
Age Related Macular Degeneration Drug: Aflibercept Drug: Ranibizumab Procedure: Combination Photodynamic Therapy

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.

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Study Type : Observational
Actual Enrollment : 30 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Neovascular Age-related Macular Degeneration: Intraocular Inflammatory Cytokines in the Non-responder to Ranibizumab Treatment
Study Start Date : August 2014
Actual Primary Completion Date : August 2016
Actual Study Completion Date : December 2016

Resource links provided by the National Library of Medicine


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 Name: 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 Name: Lucentis




Primary Outcome Measures :
  1. Aqueous Humour Cytokine Levels [ Time Frame: At time of Intravitreal Injection ]

Secondary Outcome Measures :
  1. Demographic Data [ Time Frame: At time of appointment ]
  2. Number of anti-VEGF injections before developing non-responder characteristics [ Time Frame: At time of appointment ]
  3. History of Previous Treatment [ Time Frame: At time of appointment ]
  4. Optical Coherence Tomography (OCT) results [ Time Frame: At time of appointment ]
  5. Fluorescein Angiography Results and Indocyanine Green Angiography Results [ Time Frame: At time of appointment ]

Biospecimen Retention:   Samples Without DNA
Aqueous Humour from Eye


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02218177


Locations
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Canada, Ontario
Toronto Western Hospital
Toronto, Ontario, Canada, M2N4H3
Sponsors and Collaborators
University Health Network, Toronto
Investigators
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Principal Investigator: Wai-Ching Lam, MD Toronto Western Hospital, University Health Network, University of Toronto
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Wai-Ching Lam, Professor University of Toronto, Residency Program Director Dept. of Ophthalmology, Continuing Medical Education Director Dept. of Ophthalmology, University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT02218177    
Other Study ID Numbers: VEGF wAMD cytokine study
First Posted: August 18, 2014    Key Record Dates
Last Update Posted: October 11, 2018
Last Verified: October 2018
Keywords provided by Wai-Ching Lam, University Health Network, Toronto:
wet Age Related Macular Degeneration
Ranibizumab
Aflibercept
Combination Photodynamic Therapy
Cytokine analysis
Additional relevant MeSH terms:
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Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
Ranibizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents