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Intraocular Cytokine in Recurrence of Polypoidal Choroidal Vasculopathy (CyPov)

Primary Purpose

Exudative Age-related Macular Degeneration, Polypoidal Choroidal Vasculopathy

Status
Unknown status
Phase
Phase 4
Locations
Korea, Republic of
Study Type
Interventional
Intervention
ranibizumab
Sponsored by
Pusan National University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Exudative Age-related Macular Degeneration

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Submacular PCV diagnosed based on branching neovascular networks having polypoidal dilatation in ICGA.
  2. Presence of exudative changes involving the fovea in OCT
  3. Decreased visual acuity to 20/320 - 20/40 to be primarily the results of PCV in the study eye.
  4. Willing and able to comply with clinic visits and study-related procedures, and provide a signed informed consent form.

Exclusion Criteria:

  1. Extramacular PCV.
  2. Presence of pathologic changes blocking 50% or more area of the lesion in angiography.
  3. Any anti-VEGF treatment in the study eye within 180 days of day 1.
  4. Previous photodynamic therapy in the study eye.
  5. History of intraocular surgery except uncomplicated cataract surgery performed before 90 days or more from day 1.
  6. Presence of exudative ARMD requiring anti-VEGF treatment in the other eye.
  7. Presence of other ocular disease that may compromise visual acuity in the study eye.
  8. Uncontrolled systemic disease.
  9. Active intraocular or periocular infection.
  10. Active intraocular inflammation.
  11. Hypersensitivity to ranibizumab or excipients.

Sites / Locations

  • Pusan National University Yangsan Hospital
  • Pusan National University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

pro-re-nata

Arm Description

Ranibizumab 0.5mg is injected in to the vitreous cavity. An injection is given every 4 weeks three times, and then the patient will be followed up every 4 weeks. An addition injection is given as needed. Recurrence is defined as increase of exudative changes, or increase of 10% or more in central subfield macular thickness (CSMT) measured using optical coherence tomography. Aqueous humor is sampled from the anterior chamber before injection at baseline, 8 weeks and 20 weeks.

Outcomes

Primary Outcome Measures

Changes of VEGF-A from 8 weeks to 20 weeks
Intraocular concentration of VEGF-A is measured using multiplex immunoassay.

Secondary Outcome Measures

Changes of the other cytokines from 8 weeks to 20 weeks
Intraocular concentration of the other cytokines including angiopoietin-1, interleukin-10 (IL-10), platelet-derived growth factor (PDGF) and placental growth factor (PlGF) is measured using multiplex immunoassay.
Changes of cytokines from baseline to 8 weeks
Intraocular concentration of cytokines including VEGF, angiopoietin-1, IL-10, PDGF and PlGF is measured using multiplex immunoassay.
Correlation between time to recurrence and cytokine concentration at baseline and 8 weeks.
Time to recurrence is defined as number of weeks from 8 to recurrence. The correlation is assessed using non-parametric analysis, or Spearman's ranked correlation.
Correlation between vision changes and cytokine concentration changes
Visual acuity is assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The ETDRS chart includes 100 letters as the maximum possible score, and 0 letters read as the minimum possible score. Visual acuity of 85 letters is equivalent to 20/20. Higher score represents better functioning. The correlation is assessed using non-parametric analysis, or Spearman's ranked correlation.
Correlation between CSMT and cytokine concentration
CSMT is central 1mm thickness of the macula measured using spectral-domain optical coherence tomography (OCT). Normal thickness is around 250μm. Increased CSMT is regarded as increase of en exudative sign. The correlation is assessed using non-parametric analysis, or Spearman's ranked correlation.
Correlation between choroidal thickness and cytokine concentration
Choroidal thickness is thickness of the choroid measured at the foveal center using spectral-domain OCT. Increased choroidal thickness was reported to be related to poor response to anti-VEGF treatment. The correlation is assessed using non-parametric analysis, or Spearman's ranked correlation.
Correlation between area of new vessels and cytokine concentration
Area of new vessels is measured in indocyanine green angiography (ICGA) obtained at baseline. The correlation is assessed using non-parametric analysis, or Spearman's ranked correlation.
Correlation between polyp closure and cytokine concentration changes
Polyp closure is defined as disappearance of polypoidal terminal in new vessels assessed in ICGA at 8 weeks. The difference of cytokine concentration is assessed between the closed group and un-closed group using non-parametric analysis, or Mann-Whitney U test.

Full Information

First Posted
November 22, 2016
Last Updated
October 8, 2019
Sponsor
Pusan National University Hospital
Collaborators
Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT02976194
Brief Title
Intraocular Cytokine in Recurrence of Polypoidal Choroidal Vasculopathy
Acronym
CyPov
Official Title
Intraocular Cytokine Changes in Recurrence of Polypoidal Choroidal Vasculopathy
Study Type
Interventional

2. Study Status

Record Verification Date
October 2019
Overall Recruitment Status
Unknown status
Study Start Date
November 22, 2016 (Actual)
Primary Completion Date
November 2019 (Anticipated)
Study Completion Date
January 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pusan National University Hospital
Collaborators
Novartis

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Changes of intraocular cytokines including vascular endothelial growth factor (VEGF) will be measured in recurrence of polypoidal choroidal vasculopathy (PCV) during treatment of ranibizumab.
Detailed Description
PCV is regarded as a subtype of age-related macular degeneration (ARMD), but has several different features such as polypoidal terminal of new vessels, and relative resistance to anti-VEGF treatment. Other cytokines then VEGF are thought to be associated with development and progression of the disease. The aim of the this study is to investigate intraocular cytokines related to recurrence of polypoidal choroidal vasculopathy. Aqueous humor will be sampled from the anterior chamber at baseline, after loading injections of ranibizumab and at recurrence. The concentration of various cytokines will be measured in the aqueous humor.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Exudative Age-related Macular Degeneration, Polypoidal Choroidal Vasculopathy

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
28 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
pro-re-nata
Arm Type
Experimental
Arm Description
Ranibizumab 0.5mg is injected in to the vitreous cavity. An injection is given every 4 weeks three times, and then the patient will be followed up every 4 weeks. An addition injection is given as needed. Recurrence is defined as increase of exudative changes, or increase of 10% or more in central subfield macular thickness (CSMT) measured using optical coherence tomography. Aqueous humor is sampled from the anterior chamber before injection at baseline, 8 weeks and 20 weeks.
Intervention Type
Drug
Intervention Name(s)
ranibizumab
Other Intervention Name(s)
Lucentis
Intervention Description
Ranibizumab 0.5mg is injected into the vitreous cavity through the pars plana using 30 gauge (or narrower) needle-attached syringe.
Primary Outcome Measure Information:
Title
Changes of VEGF-A from 8 weeks to 20 weeks
Description
Intraocular concentration of VEGF-A is measured using multiplex immunoassay.
Time Frame
8 weeks and 20 weeks
Secondary Outcome Measure Information:
Title
Changes of the other cytokines from 8 weeks to 20 weeks
Description
Intraocular concentration of the other cytokines including angiopoietin-1, interleukin-10 (IL-10), platelet-derived growth factor (PDGF) and placental growth factor (PlGF) is measured using multiplex immunoassay.
Time Frame
8 weeks and 20 weeks
Title
Changes of cytokines from baseline to 8 weeks
Description
Intraocular concentration of cytokines including VEGF, angiopoietin-1, IL-10, PDGF and PlGF is measured using multiplex immunoassay.
Time Frame
baseline and 8 weeks
Title
Correlation between time to recurrence and cytokine concentration at baseline and 8 weeks.
Description
Time to recurrence is defined as number of weeks from 8 to recurrence. The correlation is assessed using non-parametric analysis, or Spearman's ranked correlation.
Time Frame
baseline and 8 weeks
Title
Correlation between vision changes and cytokine concentration changes
Description
Visual acuity is assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The ETDRS chart includes 100 letters as the maximum possible score, and 0 letters read as the minimum possible score. Visual acuity of 85 letters is equivalent to 20/20. Higher score represents better functioning. The correlation is assessed using non-parametric analysis, or Spearman's ranked correlation.
Time Frame
baseline and 24 weeks.
Title
Correlation between CSMT and cytokine concentration
Description
CSMT is central 1mm thickness of the macula measured using spectral-domain optical coherence tomography (OCT). Normal thickness is around 250μm. Increased CSMT is regarded as increase of en exudative sign. The correlation is assessed using non-parametric analysis, or Spearman's ranked correlation.
Time Frame
baseline, 8 weeks and 20 weeks.
Title
Correlation between choroidal thickness and cytokine concentration
Description
Choroidal thickness is thickness of the choroid measured at the foveal center using spectral-domain OCT. Increased choroidal thickness was reported to be related to poor response to anti-VEGF treatment. The correlation is assessed using non-parametric analysis, or Spearman's ranked correlation.
Time Frame
baseline, 8 weeks and 20 weeks.
Title
Correlation between area of new vessels and cytokine concentration
Description
Area of new vessels is measured in indocyanine green angiography (ICGA) obtained at baseline. The correlation is assessed using non-parametric analysis, or Spearman's ranked correlation.
Time Frame
baseline
Title
Correlation between polyp closure and cytokine concentration changes
Description
Polyp closure is defined as disappearance of polypoidal terminal in new vessels assessed in ICGA at 8 weeks. The difference of cytokine concentration is assessed between the closed group and un-closed group using non-parametric analysis, or Mann-Whitney U test.
Time Frame
baseline and 8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Submacular PCV diagnosed based on branching neovascular networks having polypoidal dilatation in ICGA. Presence of exudative changes involving the fovea in OCT Decreased visual acuity to 20/320 - 20/40 to be primarily the results of PCV in the study eye. Willing and able to comply with clinic visits and study-related procedures, and provide a signed informed consent form. Exclusion Criteria: Extramacular PCV. Presence of pathologic changes blocking 50% or more area of the lesion in angiography. Any anti-VEGF treatment in the study eye within 180 days of day 1. Previous photodynamic therapy in the study eye. History of intraocular surgery except uncomplicated cataract surgery performed before 90 days or more from day 1. Presence of exudative ARMD requiring anti-VEGF treatment in the other eye. Presence of other ocular disease that may compromise visual acuity in the study eye. Uncontrolled systemic disease. Active intraocular or periocular infection. Active intraocular inflammation. Hypersensitivity to ranibizumab or excipients.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ji Eun Lee, MD, PhD
Organizational Affiliation
Pusan National University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Pusan National University Yangsan Hospital
City
Yangsan
State/Province
Gyeongsangnam-do
ZIP/Postal Code
50612
Country
Korea, Republic of
Facility Name
Pusan National University Hospital
City
Busan
ZIP/Postal Code
49241
Country
Korea, Republic of

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
24106111
Citation
Cha DM, Woo SJ, Kim HJ, Lee C, Park KH. Comparative analysis of aqueous humor cytokine levels between patients with exudative age-related macular degeneration and normal controls. Invest Ophthalmol Vis Sci. 2013 Oct 25;54(10):7038-44. doi: 10.1167/iovs.13-12730.
Results Reference
background
PubMed Identifier
27537264
Citation
Rezar-Dreindl S, Sacu S, Eibenberger K, Pollreisz A, Buhl W, Georgopoulos M, Krall C, Weigert G, Schmidt-Erfurth U. The Intraocular Cytokine Profile and Therapeutic Response in Persistent Neovascular Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci. 2016 Aug 1;57(10):4144-50. doi: 10.1167/iovs.16-19772.
Results Reference
background
PubMed Identifier
26799405
Citation
Hu J, Leng X, Hu Y, Atik A, Song X, Li Z, Liu Y, Lu L. The Features of Inflammation Factors Concentrations in Aqueous Humor of Polypoidal Choroidal Vasculopathy. PLoS One. 2016 Jan 22;11(1):e0147346. doi: 10.1371/journal.pone.0147346. eCollection 2016.
Results Reference
background
PubMed Identifier
25472810
Citation
Sakurada Y, Nakamura Y, Yoneyama S, Mabuchi F, Gotoh T, Tateno Y, Sugiyama A, Kubota T, Iijima H. Aqueous humor cytokine levels in patients with polypoidal choroidal vasculopathy and neovascular age-related macular degeneration. Ophthalmic Res. 2015;53(1):2-7. doi: 10.1159/000365487. Epub 2014 Nov 29.
Results Reference
background
PubMed Identifier
16490490
Citation
Tong JP, Chan WM, Liu DT, Lai TY, Choy KW, Pang CP, Lam DS. Aqueous humor levels of vascular endothelial growth factor and pigment epithelium-derived factor in polypoidal choroidal vasculopathy and choroidal neovascularization. Am J Ophthalmol. 2006 Mar;141(3):456-62. doi: 10.1016/j.ajo.2005.10.012.
Results Reference
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Intraocular Cytokine in Recurrence of Polypoidal Choroidal Vasculopathy

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