Microperimetry and Optical Coherence Tomography (OCT) With Lucentis for Diabetic Macular Edema (DME) - Full Text View

Sponsor:	The Ludwig Boltzmann Institute of Retinology and Biomicroscopic Laser Surgery
Information provided by:	The Ludwig Boltzmann Institute of Retinology and Biomicroscopic Laser Surgery
ClinicalTrials.gov Identifier:	NCT00885794

Purpose

Diabetic maculopathy is the leading cause of visual impairment in the working-age population in developed countries. Diabetic macular edema can cause impaired visual acuity and so far is treated by laser, vitreous surgery, and intravitreal cortisone application. Still 50% of the cases do not respond to the treatment.

Recently intraocular anti-VEGF-treatment with ranibizumab (Lucentis®, Novartis) in diabetic macular edema has proven efficacy to last over a period of 3 to 6 months. Still, the optimal dosage for those intravitreal injections still has to be found, because frequent injections are necessary.

The measurement of visual acuity is inadequate to quantify in detail the visual impairment. Using the newest technology of a high-definition optical coherence tomography (Cirrus-OCT, Carl Zeiss Meditec Inc.) to determine the retinal thickness, and a miroperimetry (MP-1, Nidek Technologies) to determine retinal sensitivity, we hope to find the optimal dosage of intravitreal anti-VEGF treatment in diabetic macular edema.

Study objective: To determine the dose response of 0.5mg and 1.0mg ranibizumab (Lucentis®, Novartis Pharma) intravitreal injection in subjects with resistant diabetic macular edema and evaluate safety and tolerability.

Condition	Intervention	Phase
Diabetic Macular Edema	Drug: Ranibizumab	Phase II Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Control: Dose Comparison Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Single Blind (Investigator) Primary Purpose: Treatment
Official Title:	Microperimetry and High-Definition-OCT in Ranibizumab Treatment for Diabetic Macular Edema (MORE-Study)

Resource links provided by NLM:

Genetics Home Reference related topics: X-linked juvenile retinoschisis

MedlinePlus related topics: Edema

Drug Information available for: Ranibizumab

U.S. FDA Resources

Further study details as provided by The Ludwig Boltzmann Institute of Retinology and Biomicroscopic Laser Surgery:

Primary Outcome Measures:

Retinal thickness [ Time Frame: at 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Retinal sensitivity [ Time Frame: 3, 6, and 9 months ] [ Designated as safety issue: Yes ]
Distance best corrected visual acuity [ Time Frame: 3, 6, and 9 months ] [ Designated as safety issue: Yes ]
Reading best corrected visual acuity [ Time Frame: 3, 6, and 9 months ] [ Designated as safety issue: Yes ]
Intraocular pressure [ Time Frame: 3, 6, and 9 months ] [ Designated as safety issue: Yes ]
Type of diabetic macular edema [ Time Frame: 3, 6, and 9 months ] [ Designated as safety issue: Yes ]
Type of diabetes mellitus HbA1c [ Time Frame: 3, 6, and 9 months ] [ Designated as safety issue: Yes ]
Blood-pressure [ Time Frame: 3, 6, and 9 months ] [ Designated as safety issue: Yes ]
Age [ Time Frame: 3, 6, and 9 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	40
Study Start Date:	May 2008
Estimated Study Completion Date:	May 2010
Estimated Primary Completion Date:	May 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
0.5 mg Ranibizumab: Experimental 3 intravitreal injections of 0.5 mg Ranibizumab every 5 weeks	Drug: Ranibizumab 3 intravitreal injection every 5 weeks
1.0 mg of Ranibizumab: Experimental 3 intravitreal injections of 1.0mg Ranibizumab every 5 weeks	Drug: Ranibizumab 3 intravitreal injection every 5 weeks

Detailed Description:

Diabetic maculopathy due to diabetic macular edema (DME) is the leading cause of visual impairment in the working-age population in developed countries. DME is the swelling of the retina resulting from the exudation and accumulation of extracellular fluid and proteins in the macula. Structural changes in the endothelium of retinal vessels lead to a breakdown of the blood-retina barrier and increase vascular permeability, resulting in exudation. The standardized treatment of DME is a focal laser or GRID-laser treatment with or without combined triamcinolone intravitreal injections. Those laser treatments produce scars in the central retina and are not always very effective. In cases of macular traction or taut posterior hyloid vitrectomy and retinal surgery are necessary.

Vascular endothelial growth factor (VEGF) has been implicated as an important factor in the occurrence of vascular permeability in DME. In patients with DME, VEGF levels are significantly elevated, compared to patients without ocular disease. Therefore, anti-VEGF treatment has been implicated as an important treatment of DME and recently intraocular anti-VEGF-treatment with ranibizumab (Lucentis®, Novartis Pharma) in diabetic macular edema has proven to be very effective. Just like in patients with age-related macular degeneration (AMD), anti-VEGF treatment was given 3 times every 4-6 weeks. The same treatment was repeated at a relapse of the disease, again 3 times every 4-6 weeks. One study group treated DME with 0.5mg ranibizumab intravitreal injections and the other compared 0.3mg to 0.5mg of ranibizumab intravitreal injections. An optimal treatment dose has not been found yet.

Visual acuity assessment is currently used to determine the functional damage caused by edema, although it may not completely describe the functional condition of the patient. Furthermore, visual acuity alone does not seem to be the best parameter to define the effect and continuation of treatment. Retinal thickness, as measured by the noninvasive optical coherence tomography (OCT) can deliver detailed information about the retinal situation during and after treatment. Also a fundus related perimetry, known as microperimetry (MP), is a useful noninvasive examination method in determining the site of relative and absolute scotomas and also fixation characteristics. With MP the macular sensitivity can be measured to further assess the macular condition.

Using the newest technology of a high-definition OCT (Cirrus-OCT, Carl Zeiss Meditec Inc.) to determine the retinal thickness, and a MP with automated correction for eye movements (MP-1, Nidek Technologies) to determine retinal sensitivity, we intend to analyze this new treatment option for DME, and find the optimized dose for intravitreal injection of ranibizumab in cases of ineffective laser treatment.

Eligibility

Ages Eligible for Study:	51 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Study eye with clinically significant macular edema, for which one of the following characteristics has to be present:
retinal thickening at or within 500µm from the center of the macula,
hard exudates at or within 500µm from the center of the macula associated with thickening of the adjacent retina,
a zone (>1-disk area) or zones of retinal thickening of which any part is within 1 disk diameter from the center of the macula.
Second line treatment after ineffective laser treatment
Men or women with diabetes mellitus
Only one eye per patient
Age > 50 years
HbA1c < 8%

Exclusion Criteria:

Study eye with concomitant retinal or choroidal disorder other than diabetic retinopathy
Study eye with significant central lens opacities and / or conditions that limit the view of the fundus
poor general condition
woman of childbearing potential, current pregnancy or breastfeeding
Patients who are unwilling to adhere to visit examination schedules
Evidence of macular traction or taut posterior hyloid.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00885794

Contacts

Contact: Ulrike Stolba, MD	+43171165 ext 4611	ulrike.stolba@wienkav.at
Contact: Katharina E Schmid-Kubista, MD	+43171165 ext 4611	katharina.schmid-kubista@wienkav.at

Locations

Austria
Rudolf Foundation Clinic	Recruiting
Vienna, Austria, 1030
Contact: Ulrike Stolba, MD +43171165 ext 4611 ulrike.stolba@wienkav.at
Contact: Katharina E Schmid-Kubista, MD +43171165 ext 4611 katharina.schmid-kubista@wienkav.at
Sub-Investigator: Katharina E Schmid-Kubista, MD

Sponsors and Collaborators

The Ludwig Boltzmann Institute of Retinology and Biomicroscopic Laser Surgery

Investigators

Principal Investigator:

Ulrike Stolba, MD

Department of Ophthalmology, Ludwig Boltzmann Institute for Retinology and Biomicroscopic Lasersurgery, Rudolf Foundation Clinic

More Information

No publications provided

Responsible Party:	Department of Ophthalmology, The Ludwig Boltzmann Institute of Retinology and Biomicroscopic Laser Surgery, Rudolf Foundation Clinic ( Priv. Doz. OA Dr. Ulrike Stolba )
ClinicalTrials.gov Identifier:	NCT00885794 History of Changes
Other Study ID Numbers:	EK 08-069-0508
Study First Received:	April 20, 2009
Last Updated:	December 3, 2009
Health Authority:	Austria: Ethikkommission

Keywords provided by The Ludwig Boltzmann Institute of Retinology and Biomicroscopic Laser Surgery:

Clinically Significant Diabetic Macular Edema
Focal Laser
GRID-Laser
Ranibizumab
Lucentis

Microperimetry
High-Definition OCT
Randomized
Observer-Blinded
Ineffective Treatment with Focal Laser or GRID-Laser

Additional relevant MeSH terms:

Edema
Macular Edema
Signs and Symptoms
Macular Degeneration

Retinal Degeneration
Retinal Diseases
Eye Diseases

ClinicalTrials.gov processed this record on September 01, 2010