Effect of Macugen(Pegaptanib)on Surgical Outcomes and VEGF Levels in Diabetic Patients With PDR (Diabetic Retinopathy or CSDME (Macular Edema) (PEGAP001)

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Thomas G. Sheidow, Lawson Health Research Institute
ClinicalTrials.gov Identifier:
NCT00446381
First received: March 8, 2007
Last updated: April 17, 2012
Last verified: April 2012
  Purpose

Patients with proliferative diabetic retinopathy or clinically significant diabetic macular edema requiring surgical intervention will receive a pre-operative injection of Macugen. An initial, pre-injection vitreous tap will be done in order to provide baseline VRGF 165 and cytokine levels. At the onset of the vitrectomy, a second vitreous sample will be taken to obtain intra-operative levels of Macugen, VEGF 165 and cytokines.


Condition Intervention
Proliferative Diabetic Retinopathy
Diabetic Macular Edema
Drug: Macugen (pegaptanib)
Drug: Macugen (Pegaptanib)

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Effect of Macugen (Pegaptanib) on Surgical Outcomes and Growth Factors Including Vascular Endothelial Growth Factor (VEGF) Levels in Patients With Proliferative Diabetic Retinopathy (PDR) and Clinically Significant Diabetic Macular Edema (CSDME)

Resource links provided by NLM:


Further study details as provided by Lawson Health Research Institute:

Primary Outcome Measures:
  • Levels of intravitreal Macugen post injection of intravitreal Macugen. [ Time Frame: 2 to 8 weeks ] [ Designated as safety issue: No ]
  • Levels of intravitreal VEGF 165 pre and post injection of intravitreal Macugen. [ Time Frame: 0 to 8 weeks ] [ Designated as safety issue: No ]
  • Levels of intravitreal VEGF, TGFbeta, ET-1, PDGF, IGF-1,angiopoietin, HIF 1 alpha, HIF 1 beta pre and post injection of intravitreal Macugen. [ Time Frame: 0 to 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Effect on ease of surgery post injection of intravitreal Macugen. [ Time Frame: 2 to 8 weeks ] [ Designated as safety issue: No ]
  • Effect on re-bleed rate post injection of intravitreal Macugen. [ Time Frame: 0 to 8 weeks ] [ Designated as safety issue: No ]
  • Effect on concomitant diabetic macular edema post injection of intravitreal Macugen [ Time Frame: 0 to 8 weeks ] [ Designated as safety issue: No ]

Enrollment: 28
Study Start Date: October 2006
Study Completion Date: September 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Patients with Proliferative Diabetic Retinopathy
Drug: Macugen (pegaptanib)
Pegaptanib 0.3 mg by intravitreal injection once pre-operatively
Experimental: 2
Patients with Clinically Significant Macular Edema
Drug: Macugen (Pegaptanib)
Pegaptanib 0.3 mg by intravitreal injection once pre-operatively.

Detailed Description:

Diabetes is one of the leading causes of blindness in North America. Diabetic retinopathy (PDR) is characterized by disruption of the normal microvascular circulation in the retina and results in the production of neovascularization and increased microvascular permeability. Similarly, clinically significant diabetic macular edema CSDME) results in loss of central visual acuity.

Many patients with these conditions, despite treatment, will go on to develop vitreous hemorrhage or tractional changes that require surgical intervention (such)as vitrectomy and/or vitrectomy with membrane peeling in the attempt to both restore vision and prevent further visual loss or re-establish the normal macular anatomy and improve patient visual acuity.

Although multiple etiologic factors are involved in the early changes seen in diabetic retinopathy and maculopathy, it has been shown that VEGF is the primary angiogenic growth factor implicated in the development of neovascularization in PRD and in increased vascular permeability, resulting in CSDME. VEGF levels have been found to correlate tightly with the extent of diabetic retinopathy and introduction of VEGF into normal primate eyes can induce diabetic retinopathy. Although several isoforms of VEGF exist, isoform 165 (VEGF 165) is the most pathogenic form of VEGF and therefore inhibition of VEGF 165 may play a significant role in modulating diabetic retinopathy and maculopathy.

Macugen is a VEGF antagonist (anti-VEGF pegylated aptamer) which binds to VEGF 165 with high specificity and affinity. In vitro pharmacology studies have shown that Macugen binds to the amino acid isoform VEGF 165 and inhibits it from binding to its cellular receptors. As a consequence, Macugen blocks signalling events and disrupts the cascade of proliferative and vascular permeability responses associated with the binding of VEGF 165 to endothelial cells. This effect has been clearly proven in Phase 3 trials for patients with age-related macular degeneration (AMD), resulting in inhibition of vascular development and decrease in vascular leakage.

Although diabetic retinopathy represents a different challenge than AMD, the underlying pathogenic factors are similar in the role and effects of VEGF. Regression of retinal neovascularization after Macugen therapy in diabetic individuals has been shown. Phase 2 studies have been completed and Phase 3 studies are currently underway in patients with diabetic macular edema to evaluate the efficacy of Macugen to restore vision in patients with CSDME. These studies are ongoing but exclude patients in whom vitrectomy has been performed or is planned in the near future due to tractional effects on the macula from epiretinal membranes or vitreomacular traction syndrome. No studies have been done to date in patients with PDR or CSDME to quantify the reduction of intravitreal VEGF 165 levels in these patients following intravitreal Macugen injection or to evaluate the effects of VEGF 165 blockade on the neovascular regression and surgical outcome in patients with extensive diabetic proliferative neovascularization.

The goal of this study is to quantify the reduction of intravitreal VEGF 165 levels in patients following intravitreal Macugen injection pre-operatively and determine the level of Macugen in the vitreous cavity after variable time intervals (2,4, 6 or 8 weeks).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 18 years or older
  • Type 1 or 2 diabetes
  • patients requiring surgical intervention for complications of proliferative diabetic retinopathy with vitreous hemorrhage or traction retinal detachment or clinically significant macular edema
  • women postmenopausal for 12 months before the study, surgically sterile, or not pregnant and on effective contraception.

Exclusion Criteria:

  • previous retinal vein occlusion.
  • any intraocular surgery within the previous 12 months.
  • myopia of > or = to 8 diopters.
  • active ocular or periocular infection
  • treatment with an investigational agent for any condition 60 days prior to enrollment.
  • evidence of severe cardiac disease.
  • clinically significant peripheral vascular disease (previous surgery, amputation, or symptoms of claudication)
  • uncontrolled hypertension (treated systolic blood pressure > 155 mmHg or diastolic blood pressure > 95 mmHg)
  • stroke within the preceding 12 months.
  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: NCT00446381

Locations
Canada, Ontario
Ivey Eye Institute, St. Joseph's Health Care Centre
London, Ontario, Canada, N6A 4G5
Sponsors and Collaborators
Lawson Health Research Institute
Pfizer
Investigators
Principal Investigator: Thomas G. Sheidow, MD Ivey Eye Institute, St. Joseph's Health Care Centre
  More Information

No publications provided

Responsible Party: Thomas G. Sheidow, MD, FRCSC, Ophthalmologist, Vitreoretinal Surgeon, Lawson Health Research Institute
ClinicalTrials.gov Identifier: NCT00446381     History of Changes
Other Study ID Numbers: R-06-821, Health Canada Control #108753
Study First Received: March 8, 2007
Last Updated: April 17, 2012
Health Authority: Canada: Health Canada

Keywords provided by Lawson Health Research Institute:
Proliferative Diabetic Retinopathy
Clinically Significant Diabetic Macular Edema
VEGF
Macugen (pegaptanib)

Additional relevant MeSH terms:
Edema
Diabetic Retinopathy
Retinal Diseases
Macular Edema
Signs and Symptoms
Eye Diseases
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Macular Degeneration
Retinal Degeneration

ClinicalTrials.gov processed this record on September 16, 2014