Vitreous Levels of Cysteine-rich 61 in Patients With Proliferative Diabetic Retinopathy (VL)

To determine the vitreous levels of fractalkine, cysteine-rich 61 (Cyr61), and VEGF in patients with PDR. Verifying that it is greater to that found in non-diabetic patients with different non-angiogenetic diseases.

Study Overview

• Status: Completed
• Conditions: Proliferative Diabetic Retinopathy
• Intervention / Treatment: Drug: intravitreal injection of 1.25 mg of bevacizumab

Detailed Description

Introduction:

Angiogenesis, the growth and proliferation of new blood vessels, is an important aspect of the vascular proliferation found in tumor growth, wound repair, inflammatory states, and ischemic sequel in the ocular angiogenetic diseases. Intraocular neovascularization, the major eventually complication of diabetic mellitus, may result in vitreous hemorrhage, tractional retinal detachment, neovascularization glaucoma and eventually blindness. The involved factors include basic fibroblast growth factor (bFGF), insulin-like growth factor-I (IGF-I), vascular endothelial cell growth factor (VEGF), and Connective tissue growth factor (CTGF)/Cysteine-rich protein (Cyr61)/Nephroblastoma overexpressed gene (CCN) family. VEGF is a primary angiogenic factor that mediates ischemic-induced retinal neovascularization. VEGF level are elevated in the vitreous fluid in patients with proliferative diabetic retinopathy (PDR). The unselective anti-VEGF antibody bevacizumab has been used for the treatment of diabetic retinopathy.

Problem:

In spite of its potent anti-VEGF property, it does not completely inhibit ischemia-induced retinal neovascularization. Several other factors which were detected to have increased vitreous levels in the PDR patients might participate in the angiogenic process of diabetic retinopathy. One of the member of the CCN family, connective tissue growth factor (CTGF), was found to be involved in the angiogenesis and fibrosis mechanism of PDR. It is unclear if the other factors in the CCN family might also control the development of retinal angiogenesis and fibrosis.We measured vitreous cysteine-rich 61 (Cyr61) levels in PDR patients, non-diabetic patients,and PDR patients pretreated with bevacizumab. We further correlated the cysteine-rich 61 levels with different stages of PDR. Concomitant VEGF level was also measured to better understand the interaction of different factors.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • Department of Ophthalmology, National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18 years
• Patients with type 1 or type 2 diabetes mellitus
• Not eligible for any currently approved treatments or experimental protocols
• Patients with PDR who receiving vitreoretinal surgery.

Exclusion Criteria:

• A condition that would preclude a patient for participation in the study in opinion of investigator, e.g., unstable medical status including glycemic control and blood pressure
• Panretinal laser photocoagulation in the study eye
• Previous treatment with intravitreal or sub-Tenon triamcinolone
• History of submacular surgery or other surgical intervention for diabetic

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: pretreatment of bevacizumab; Patients will receive intravitreal injection of 1.25 mg of bevacizumab (0.05 ml) 7 to 9 days before vitrectomy due to diabetic retinopathy.	Drug: intravitreal injection of 1.25 mg of bevacizumab; Patients will receive intravitreal injection of 1.25 mg of bevacizumab (0.05 ml) 7 to 9 days before vitrectomy; Other Names: Bevacizumab(Avastin, Genentech, Inc., South San Francisco)
NO_INTERVENTION: No pretreatment of bevacizumab; Patients will not receive bevacizumab pretreatment before vitreous surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Vitreous levels of Fractalkine, Cyr61, and VEGF of patients with proliferative diabetic retinopathy	7 days

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Chung-Hao Yang, MD, PhD, National Taiwan University Hospital

Publications and helpful links

General Publications

• Watanabe D, Suzuma K, Matsui S, Kurimoto M, Kiryu J, Kita M, Suzuma I, Ohashi H, Ojima T, Murakami T, Kobayashi T, Masuda S, Nagao M, Yoshimura N, Takagi H. Erythropoietin as a retinal angiogenic factor in proliferative diabetic retinopathy. N Engl J Med. 2005 Aug 25;353(8):782-92. doi: 10.1056/NEJMoa041773.

Study record dates

Study Major Dates

• Study Start: January 1, 2005
• Primary Completion (ACTUAL): December 1, 2006
• Study Completion (ACTUAL): December 1, 2006

Study Registration Dates

• First Submitted: August 8, 2013
• First Submitted That Met QC Criteria: August 12, 2013
• First Posted (ESTIMATE): August 13, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): August 13, 2013
• Last Update Submitted That Met QC Criteria: August 12, 2013
• Last Verified: January 1, 2004

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Endocrine System Diseases; Diabetic Angiopathies; Diabetes Complications; Diabetes Mellitus; Retinal Diseases; Diabetic Retinopathy; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: NSC96-2628-B-002-032-MY3