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The Efficacy of Intravitreal Aflibercept Injection in Improvement of Retinal Nonperfusion in Diabetic Retinopathy

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ClinicalTrials.gov Identifier: NCT03006081
Recruitment Status : Recruiting
First Posted : December 30, 2016
Last Update Posted : December 30, 2016
Sponsor:
Information provided by (Responsible Party):
Young Hee Yoon, Asan Medical Center

Brief Summary:
Retinal nonperfusion drives vision-threatening complications such as pathological neovascularization, which can lead to neovascular glaucoma, vitreous hemorrhage, or tractional retinal detachments and macular edema in diabetic retinopathy. Thus, decreasing nonperfusion area with aid of anti-VEGF agents might be a useful way to prevent deteriorating course of diabetic retinopathy. The main purpose of this study is to determine the efficacy of intravitreal aflibercept injection in improvement of retinal nonperfusion and identify associated factors in patients with nonproliferative diabetic retinopathy with moderate retinal nonperfusion.

Condition or disease Intervention/treatment Phase
Diabetic Retinopathy Drug: Intravitreal Aflibercept injection Phase 2

Detailed Description:

Retinal nonperfusion drives vision-threatening complications such as pathological neovascularization, which can lead to neovascular glaucoma, vitreous hemorrhage, or tractional retinal detachments and macular edema in various retinal vascular diseases including diabetic retinopathy and retinal vein occlusion. Silva et al revealed that retinal nonperfusion area was correlated highly with diabetic retinopathy severity in their recent paper. It should be clarified that retinal nonperfusion is not synonymous with retinal ischemia, which implies tissue hypoxia, but is a useful surrogate.

Retinal nonperfusion has known to be associated with the production of vascular endothelial factor (VEGF). Recently, Campochiaro et al reported that neutralization of VEGF using ranibizumab improved macular edema and reversed the worsening of retinal nonperfusion in patients with retinal vein occlusion and diabetic macular edema. The precise mechanism for improved perfusion in the VEGF treated eye is uncertain. The authors suggested that VEGF exacerbates retinal ischemia by increasing leukostasis, and intravitreal anti-VEGF agents may break the feedback loop, allowing reperfusion to occur. There might be a portion of circulation that is closed but not permanently, and this reversible closure is modulated by VEGF.

The study by Campochiaro et al, however, was limited in that they reviewed retinal nonperfusion within a template consisting of the Early Treatment Diabetic Retinopathy subfields mainly confined to posterior pole of the fundus. Wide-field retinal imaging is an imaging technique that allows a view of almost 200° of the fundus in a single image. It has been well shown that wide-field scans allow the detection of peripheral pathology that may be missed on 75 degrees of achieved by montaging the Early Treatment Diabetic Retinopathy Study 7-standard fields.

To investigators knowledge, there has been no previous study evaluating the longitudinal change of retinal nonperfusion after aflibercept treatment in a larger area of the retina by taking advantage of the 200° field of view in diabetic retinopathy. The main purpose of this study is to determine the efficacy of intravitreal aflibercept injection in improvement of retinal nonperfusion and identify associated factors in patients with nonproliferative diabetic retinopathy with moderate retinal nonperfusion.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Efficacy of Intravitreal Aflibercept Injection in Improvement of Retinal Nonperfusion in Patients With Diabetic Retinopathy
Study Start Date : May 2016
Estimated Primary Completion Date : June 2017
Estimated Study Completion Date : June 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 2mg intravitreal aflibercept injection
2mg intravitreal aflibercept (Eylea) injection at baseline, 1M, 2M, 3M, 4M, and 5M
Drug: Intravitreal Aflibercept injection
Six number of injections at baseline, 1M, 2M, 3M, 4M, and 5M
Other Name: Eylea




Primary Outcome Measures :
  1. Improvement of retinal nonperfusion [ Time Frame: 1 year ]
    Mean changes (%) of retinal nonperfusion (Ischemic index) from baseline


Secondary Outcome Measures :
  1. progression of diabetic retinopathy to proliferative diabetic retinopathy (PDR) [ Time Frame: 1 year ]
    Number of patients who receive rescue treatment due to PDR and time to rescue treatment due to PDR

  2. development of diabetic macular edema [ Time Frame: 1 year ]
    Number of patients who receive rescue treatment due to DME and time to rescue treatment due to DME

  3. Factors associated with the progression of retinal nonperfusion 1 (Functional) [ Time Frame: 1 year ]
    - Visual acuity parameters: Mean changes of BCVA from baseline at every 3 month visit The proportion of subjects with gaining / losing ≥ 15letters or more in BCVA

  4. Factors associated with the progression of retinal nonperfusion 2 (Anatomical) [ Time Frame: 1 year ]
    - Optical coherence tomography (OCT) parameters: Mean changes of Central Retinal Thickness (CRT) from baseline at every 3 month visit Mean changes of Central Retinal Volume from baseline at every 3 month visit Mean change subfoveal choroidal thickness (SFChT) from baseline at every 3 month visit

  5. Factors associated with the progression of retinal nonperfusion 3 (Anatomical) [ Time Frame: 1year ]
    - Fluorescein angiography (FA) parameters: Baselinenonperfusion area(Ischemic index) at posterior and peripheral retina Baseline degree of vascular leakage at posterior and peripheral retina


Other Outcome Measures:
  1. Safety outcome; Adverse effect of intravitreal aflibercept (Eylea) injection [ Time Frame: 1 year ]
    Ocular and systemic adverse event



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

Inclusion Criteria:

  • A subject must meet the following criteria to be eligible for inclusion in the study:

    1. Adults ≥ 18 years with type 1 or 2 diabetes mellitus
    2. Patients diagnosed as nonproliferative diabetic retinopathy with retinal nonperfusion (Ischemic index >20%) Severe nonproliferative diabetic retinopathy - Early proliferative diabetic retinopathy
    3. Willing and able to comply with clinic visits and study-related procedures
    4. Provide a signed informed consent form

Exclusion Criteria:

  • A subject who meets any of the following criteria will be excluded from the study.

    1. Systemic exclusion criteria 1. Renal failure requiring hemodialysis or peritoneal dialysis within 6 months prior to baseline or anticipated need for hemodialysis, peritoneal dialysis at any time during the study 2. Acute cardiovascular events (acute myocardiac infarction and/or cerebral infarction) within 1 year before Visit 1 3. Blood HbA1c level greater than 12% at Visit 0
    2. Ocular exclusion criteria
    1. Diabetic macular edema involving the center of the macula (Defined as the area of the center subfield of OCT, Heidelberg Spectralis: ≥305 in women; ≥320 in men) in the study eye
    2. Presence of rubeosis (neovascularization of the iris or the angle) in the study eye
    3. Any current or history of retinal diseases that affects visual acuity in the study eye
    4. Previous treatment of panretinal photocoagulation
    5. Previous treatment with anti-VEGF in study eye within 6 months before Visit 1
    6. Previous treatment with intraocular or periocular corticosteroids in the study eye within 6 months before Visit 1
    7. Previous history of intraocular surgery other than cataract surgery in the study eye
    8. Cataract surgery within 3 months before Visit 1 in the study eye
    9. Yttrium-aluminium-garnet (YAG) capsulotomy in the study eye within 1 month before Visit 1
    10. Aphakia in the study eye
    11. Elevated intraocular pressure (≥ 22 mmHg) in spite of using topical IOP lowering agents at Visit 1 or a diagnosis of glaucoma (Visual field defect corresponding to glaucomatous optic neuropathy) in the study eye
    12. Presence of a visually significant cataract in the study eye
    13. BCVA score < 34 letters in the fellow eye
    14. Hypersensitivity to aflibercept
    15. Ocular or periocular infection
    16. Active intraocular inflammation

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): NCT03006081


Contacts
Contact: Yoon Jeon Kim, MD 82-2-3010-3680 anne215@gmail.com

Locations
Korea, Republic of
Asan medical center Recruiting
Olympicro 43 gil 88, Seoul, Korea, Republic of, 05505
Contact: Young Hee Yoon, MD    82-2-3010-3680      
Sponsors and Collaborators
Asan Medical Center
Investigators
Principal Investigator: Young Hee Yoon Asan Medical Center

Publications:
Responsible Party: Young Hee Yoon, Professor, Asan Medical Center
ClinicalTrials.gov Identifier: NCT03006081     History of Changes
Other Study ID Numbers: FLOW_001
First Posted: December 30, 2016    Key Record Dates
Last Update Posted: December 30, 2016
Last Verified: December 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Keywords provided by Young Hee Yoon, Asan Medical Center:
Retinal nonperfusion
Aflibercept

Additional relevant MeSH terms:
Retinal Diseases
Diabetic Retinopathy
Eye Diseases
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases