Anterior and Posterior Segment Vascular Changes Following Laser and Anti-Vascular Endothelial Growth Factor (VEGF) Treatment of Diabetic Retinopathy

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by University of Toronto
Sponsor:
Collaborator:
Ontario Research Fund
Information provided by (Responsible Party):
Chris Hudson, University of Toronto
ClinicalTrials.gov Identifier:
NCT01196325
First received: September 3, 2010
Last updated: January 23, 2013
Last verified: January 2013
  Purpose

The study will investigate changes in the structure and function of blood vessels in the front and back of the eye following laser and anti-VEGF treatments for sight-threatening diabetic eye disease. Sixty four volunteers will be recruited, including age-matched control subjects and diabetic patients who require conventional or contemporary treatment for pre-existing diabetic eye disease. Volunteers will be assessed before and after treatment using state-of-the-art techniques to measure vision, the rate of blood flow and structure at the front and back of the eye and the effectiveness of blood flow delivery. Changes following treatment in these novel, non-invasive techniques will be quantified and described. We anticipate that conventional and new / developing treatments will lead to narrowing of the vessels and consequent reduction of blood flow at the back and front of the eye. There will be a strong relationship between structural changes of the eye and functional changes of blood vessels at the front and back of the eye. The results of this study will improve our understanding of the impact of the various treatments on the entire eye. The research will also ensure an improved understanding of the mechanisms of action of the various treatments and will provide insight of reasons for good or poor outcomes, based upon specific changes in structure and blood flow.


Condition
Diabetic Macular Edema

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Anterior and Posterior Segment Vascular Changes Following Laser and Anti-Vascular Endothelial Growth Factor (VEGF) Treatment of Diabetic Retinopathy.

Resource links provided by NLM:


Further study details as provided by University of Toronto:

Primary Outcome Measures:
  • Quantitative inner retinal blood flow [ Time Frame: Baseline, 3, 7, 30 days and 3 months ] [ Designated as safety issue: No ]
    Inner retinal blood flow will be measured using Canon Laser Blood Flowmeter


Secondary Outcome Measures:
  • Mean retinal thickness for an annulus centered on fovea [ Time Frame: Baseline,3,7,30 days, and 3 months ] [ Designated as safety issue: No ]
    Mean retinal thickness will be measured using Heidelberg Spectralis Spectral Domain Optical Coherence Tomography

  • Best Corrected Visual Acuity (LogMAR, EDTRS) [ Time Frame: Baseline, 3, 7, 30 days and 3 months ] [ Designated as safety issue: No ]
    Best Corrected Visual Acuity will be examined using 96% and 10 % contrast EDTRS letter charts.

  • Quantitative anterior blood flow [ Time Frame: Baseline, 3, 7, 30 days and 3 months ] [ Designated as safety issue: No ]
    Quantitative anterior blood flow will be assessed by measuring velocity of individual rbc's (μm/sec) and blood oxygen saturation(%)

  • Mean angle opening distance and trabecular-iris spur area [ Time Frame: Baseline, 3, 7, 30 days and 3 months ] [ Designated as safety issue: No ]
    Mean angle opening distance and trabecular-iris spur area will be measured by Heidelberg Slit-Lamp Optical Coherence Tomography.


Estimated Enrollment: 64
Study Start Date: July 2009
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
Laser Group
Patients who are clinically indicated for the laser treatment
Anti-VEGF Group (Bevacizumab)
Patients who are clinically indicated for the intravitreal injection of Bevacizumab
Anti-VEGF Group (Ranibizumab)
Patients who are clinically indicated for intravitreal injection of Ranibizumab
Age-matched controls
Group of non-diabetic participants who will be age and gender matched

Detailed Description:

Diabetic Retinopathy (DR) is the single leading cause of blindness in people of working age. The total number of people living with diabetes in Canada is well over 2 million. The WHO estimates that around 12% of people with diabetes are blind or will develop severe vision loss. The two most common treatments of DR are: Laser Photocoagulation and anti-VEGF intravitreal injection. Clinical evidence demonstrates that these treatments lead to morphological and vascular retinal changes, however the actual mechanism and nature of post treatment changes is not fully understood. It is only recently that objective and quantitative imaging and hemodynamic technologies with previously unachievable resolution have become available that enable us to evaluate and to compare various effects of these treatments on vital eye structures.

We are proposing to take advantage of these state-of-the-art technologies in order to explore unknown effects of treatments on vital eye structures. We hypothesize that: 1) Laser Photocoagulation and anti-VEGF treatments will result in vessel constriction and hence reduction in posterior (retinal and choroidal) and anterior (conjunctival) ocular blood flow; 2) Changes in anterior segment ocular morphology and blood flow will positively correlate with changes in posterior segment morphology and blood flow; 3) Combined treatments will result in a greater reduction in posterior and anterior blood flow than any single treatment; 4) There will be differences in anterior and posterior blood flow outcomes and in anterior segment oxygen saturation when compared to healthy controls.

The study will include four groups of participants: Laser treatment group; Intravitreal injection of Bevacizumab treatment group; Intravitreal injection of Ranibizumab treatment group; Healthy age matched controls. The administration of ranibizumab and bevacizumab will be randomized across participants. Randomization number will be assigned to each participant and recorded in a Master Randomization Assignment List. All patients will be recruited from the Retina Clinics of the Toronto Western Hospital.

Every type 2 diabetic patient with Diabetic Macular Edema will be assessed prior to treatment and followed-up on the 3rd, 7th,30th day and 3 months after the initial treatment.

  Eligibility

Ages Eligible for Study:   35 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Type 2 diabetic patients with clinically sight-threatening Diabetic Macular Edema will be recruited from the Retina Clinics of Toronto Western Hospital.

Criteria

Inclusion Criteria:

  • Age range of 35-75 yrs
  • Type 2 diabetes apart from age-matched control group
  • Visual acuity of 20/400 or better
  • Confirmed diagnose of Clinical Significant Diabetic Macular Edema (applies for Diabetic Groups only)
  • Previously untreated eye for retinal diseases and disorders

Exclusion Criteria:

  • Distance refractive error > ± 6.00 DS & / or ± 2.50 DC
  • Intraocular pressure ≥ 22mm Hg
  • Proliferative Diabetic Retinopathy
  • Any other active eye disease and disorder
  • Participants with history of cardiovascular events, stroke, thromboembolic events, transient ischemic attack, uncontrolled hypertension.
  • Any active ocular infection;
  • History of glaucoma;
  • Known allergy, hypersensitivity or contraindication to the study medication;
  • Pregnancy, breast feeding, or women of childbearing potential who are not using a reliable method of contraception;
  • Proteinuria and/or renal impairment;
  • Surgery within the past 28 days.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01196325

Contacts
Contact: Olena Puzyeyeva, MD (416)603-5694 ext 5694 opuzyeye@uhnresearch.ca
Contact: Lee-Anne Khuu, MSc (416)603-5694 ext 5694 lkhuu@uhnresearch.ca

Locations
Canada, Ontario
Toronto Western Hospital Recruiting
Toronto, Ontario, Canada, M5T2S8
Contact: Olena Puzyeyeva, MD    (416)603-5694    opuzyeye@uhnresearch.ca   
Contact: Lee-Anne Khuu, MSc    (416)603-5694    lkhuu@uhnresearch.ca   
Principal Investigator: Christopher Hudson, PhD         
Sub-Investigator: Michael Brent, MD         
Sub-Investigator: John G Flanagan, PhD         
Sub-Investigator: Wai-Ching Lam, MD         
Sub-Investigator: Robert G Devenyi, MD         
Sub-Investigator: Mark Mandelcorn, MD         
Sub-Investigator: Efrem Mandelcorn, MD         
Sponsors and Collaborators
University of Toronto
Ontario Research Fund
Investigators
Principal Investigator: Christopher Hudson, PhD University of Toronto
  More Information

No publications provided

Responsible Party: Chris Hudson, Professor, University of Toronto
ClinicalTrials.gov Identifier: NCT01196325     History of Changes
Other Study ID Numbers: 09-0258-BE
Study First Received: September 3, 2010
Last Updated: January 23, 2013
Health Authority: Canada: Health Canada
Canada: Ethics Review Committee

Keywords provided by University of Toronto:
Diabetes
Diabetic Macular Edema
Laser
Anti-VEGF
Morphology
Blood Flow
Vision

Additional relevant MeSH terms:
Diabetic Retinopathy
Edema
Macular Edema
Retinal Diseases
Eye Diseases
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Signs and Symptoms
Macular Degeneration
Retinal Degeneration
Mitogens
Endothelial Growth Factors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 27, 2014