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NSAID Phase II for Non-central Involved Diabetic Macular Edema (DME)

Information source: Diabetic Retinopathy Clinical Research Network
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Diabetic Macular Edema

Intervention: nepafenac 0.1% drops (Drug); Nepafenac Vehicle (Other)

Phase: Phase 2

Status: Completed

Sponsored by: Diabetic Retinopathy Clinical Research Network

Official(s) and/or principal investigator(s):
Scott M Friedman, MD, Principal Investigator, Affiliation: Florida Retina Consultants

Summary

This study is being conducted to assess the effects of topical nonsteroidal anti-inflammatories (NSAIDs) on macular retinal volume compared with placebo in eyes with non-central diabetic macular edema (DME). A secondary objective of this study is to assess the effects of topical NSAIDs on central subfield thickness and to compare the progression of non-central DME to central DME as determined by optical coherence tomography (OCT) and stereoscopic fundus photographs. Furthermore, this phase II study is being conducted (1) to determine whether the conduct of a phase III trial has merit based on an anatomic outcome, (2) to estimate recruitment potential of a phase III investigation, and (3) to provide information on outcome measures needed to design a phase III trial. The study is not designed to establish the efficacy of NSAIDs in the treatment of non- central DME.

Clinical Details

Official title: A Phase II Evaluation of Topical Non-steroidal Anti-inflammatories in Eyes With Non Central Involved Diabetic Macular Edema

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome: Mean Change in Optical Coherence Tomography Measure Retinal Volume, mm3

Secondary outcome:

Corneal Ulceration

Corneal Melting

Irritation

Mean Change in Visual Acuity

Change in OCT Central Subfield Thickness

Change in Number of Thickened Subfields on OCT

Change in Level of Diabetic Retinopathy on Stereoscopic Fundus Photographs

Detailed description: There is strong evidence to indicate that prevention of non-central involved DME from progression into the central subfield of the macula is a good anatomic surrogate for preventing visual acuity loss. Furthermore, the prevalence of macular edema is estimated to be high among patients with diabetes, and it is likely that approximately 25% of non-central involved cases of DME extend into the central subfield of the macula within one year. Thus, if a relatively safe and economical treatment could be identified that reduced the progression of non-central involved edema to central-involved edema by at least 50%, this treatment could have a major public health impact. There is also evidence that inflammation has a role in DME, and that a topical NSAID might have an effect on retinal edema. Topical NSAIDs are in current widespread clinical use and appear to be well tolerated and safe when administered chronically, making them a potentially attractive alternative treatment for DME in patients who would like to delay or avoid laser photocoagulation or intravitreal injections (for example, patients who are willing to use daily eye drops to avoid ocular procedures or patients for whom access to experienced retinal specialists to apply laser photocoagulation or other treatments is limited). This phase II trial may provide proof of concept evidence that topical NSAID treatment can have a beneficial effect on DME and possibly prevent increases in retinal volume or progression of non central-involved DME into the central subfield of the macula. Furthermore, it could determine the correlation between OCT and fundus photographic documentation of progression of DME into the central subfield in this clinical trial setting. Since effective treatments, including laser photocoagulation and intravitreal injections, already exist for DME treatment, topical NSAIDs would have to demonstrate a substantial effect on DME progression in order to be of sufficient clinical interest for further investigation. If a beneficial effect is apparent in this trial, which utilizes a relatively small sample size and short follow-up period, results from this phase II study might be utilized in planning future phase III trials. These future phase III trials could definitively answer whether or not NSAIDs are an efficacious novel therapeutic approach to the treatment of DME or preventing the progression of DME from extending into the central subfield of the macula.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Age >18 years

- Type 1 or type 2 diabetes

- Only one study eye per subject may be enrolled. The study eye must meet the

following:

- Best corrected E-ETDRS visual acuity letter score ≥ 74 (i. e., 20/32 or better)

within 8 days of enrollment.

- On clinical exam, definite retinal thickening due to DME within 3000 μm of the

center of the macula but not involving the central subfield.

- Thickened non-central macular subfields on DRCR. net approved spectral domain OCT

macular map.

- Central subfield thickness within threshold definition for normal central

subfield thickness on DRCR. net approved spectral domain OCT machine.

- No focal/grid laser within the last 6 months or other treatment for DME within

the last 4 months.

- No anticipated need to treat DME during the course of the study, unless the eye

meets the criteria for treatment (Central subfield retinal thickness increases to 310 μm or more in spectral domain OCT machine from baseline).

- Diagnosis of diabetes mellitus (type 1 or type 2). Any one of the following will be

considered to be sufficient evidence that diabetes is present:

- Current regular use of insulin for the treatment of diabetes.

- Current regular use of oral anti-hyperglycemia agents for the treatment of

diabetes.

- Documented diabetes by American Diabetes Association and/or the World Health

Organization criteria.

- At least one eye meets the study eye criteria.

- Able and willing to provide informed consent.

- Successful completion of the run-in phase during which level of compliance is more

than 80% Study Eye Inclusion Criteria

- Best corrected E-ETDRS visual acuity letter score ≥74 (i. e.20/32 or better) within 8

days of randomization.

- On clinical exam, definite retinal thickening due to DME within 3000 μm of the center

of the macula but not involving the central subfield.

- Thickened non-central macular subfields on spectral domain OCT macular map that meet

either of the following criteria:

- At least two non-central macular subfields with OCT thickness above threshold

(average normal + 2 SD) from DRCR. net approved spectral domain OCT machines- see below.

- At least one non-central macular subfield with OCT thickness at least 15 μm

above threshold (average normal + 2 SD) from DRCR. net approved spectral domain OCT machines—see DRCR. net procedures manual for threshold details.

- Central subfield thickness <250 microns obtained by one of the following DRCR. net

approved spectral domain OCT machines:

- Zeiss Cirrus

- Heidelberg Spectralis

- Optovue RTVue

- Media clarity, pupillary dilation, and study participant cooperation sufficient for

adequate OCT and fundus photographs.

- If the study participant is on multiple ocular drops, investigator believes that

study participant can be compliant with a multi-drop regimen. Exclusion Criteria: A study participant is not eligible for the run-in phase or the randomized trial if any of the following exclusion criteria are present:

- A condition that, in the opinion of the investigator, would preclude participation in

the study (e. g., unstable medical status including blood pressure, cardiovascular disease, and glycemic control).

- Subjects in poor glycemic control who, within the last 4 months, initiated intensive

insulin treatment (a pump or multiple daily injections) or plan to do so in the next 4 months should not be enrolled.

- Use of systemic corticosteroids or anti-VEGF therapy.

- Current use of prescription systemic NSAIDs.

- History of auto-immune diseases such as rheumatoid arthritis.

- Participation in an investigational trial that involved treatment with any drug

within 30 days of randomization that has not received regulatory approval at the time of study entry.

- Note: study participants cannot receive another investigational drug while

participating in the study.

- Known allergy to any component of the study drug.

- Blood pressure > 180/110 mmHg (systolic above 180 or diastolic above 110 mmHg)

- If blood pressure is brought below 180/110 by anti-hypertensive treatment, study

participant can become eligible.

- Participant is expecting to move out of the area of the clinical center to an area

not covered by another clinical center during the 12 months of the study.

- For women of child-bearing potential: pregnant or lactating or intending to become

pregnant within the next 12 months.

- Women who are potential study participants should be questioned about the potential

for pregnancy. Investigator judgment is used to determine when a pregnancy test is needed. Study Eye Exclusion Criteria

- History of focal/grid laser within the last 6 months or other treatment for DME

within the last 4 months

- Note: Throughout the study, the distribution of subjects with prior treatment for

DME will be evaluated, and eligibility criteria may be tailored to add balance between subjects with prior treatment and subjects without prior treatment for DME.

- Anticipated need to treat DME during the course of the study (Any DME treatment

during the study should follow criteria in section 4. 3).

- History of use of NSAID eye drops within the last 30 days or anticipated need for

such drops during the study due to other ocular condition

- History of panretinal (scatter) photocoagulation (PRP) within 4 months prior to

randomization

- Anticipated need for PRP in the 6 months following randomization

- Anticipated need for cataract extraction surgery in the study eye during the study

period

- Lipid in the fovea (center of the macula)

- History of major ocular surgery (including scleral buckle, any intraocular surgery,

etc.) within prior 4 months or major ocular surgery anticipated within the next 6 months following randomization

- An ocular condition, other than diabetic macular edema, is present such that, in the

opinion of the investigator, visual acuity might be affected now (e. g., foveal atrophy, pigment abnormalities, dense subfoveal hard exudates, non-retinal condition, epiretinal membrane or vitreo-macular traction) or during the course of the study (e. g., vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, etc.)

- History of YAG capsulotomy performed within 2 months prior to randomization

- Exam evidence of severe external ocular infection, including conjunctivitis,

chalazion, or substantial blepharitis

- Aphakia

- History of vitrectomy for any reason

- History of cataract surgery within the prior 1 year

- Uncontrolled glaucoma

Locations and Contacts

Loma Linda University Health Care, Dept. of Ophthalmology, Loma Linda, California 92354, United States

Southern California Desert Retina Consultants, MC, Palm Springs, California 92262, United States

California Retina Consultants, Santa Barbara, California 93103, United States

Bay Area Retina Associates, Walnut Creek, California 94598, United States

Retinal Consultants of Southern California Medical Group, Inc., Westlake Village, California 91361, United States

Retina Consultants of Southwest Florida, Fort Myers, Florida 33912, United States

Central Florida Retina Institute, Lakeland, Florida 33805, United States

Southeast Retina Center, P.C., Augusta, Georgia 30909, United States

Retina Associates of Hawaii, Inc., Honolulu, Hawaii 96813, United States

Raj K. Maturi, M.D., P.C., Indianapolis, Indiana 46290, United States

American Eye Institute, New Albany, Indiana 47150, United States

Wolfe Eye Clinic, West Des Moines, Iowa 50266, United States

Retina and Vitreous Associates of Kentucky, Lexington, Kentucky 40509-1802, United States

Paducah Retinal Center, Paducah, Kentucky 42001, United States

Elman Retina Group, P.A., Baltimore, Maryland 21237, United States

Joslin Diabetes Center, Boston, Massachusetts 02215, United States

Henry Ford Health System, Dept of Ophthalmology and Eye Care Services, Detroit, Michigan 48202, United States

Vitreo-Retinal Associates, Grand Rapids, Michigan 49525, United States

University of Minnesota, Minneapolis, Minnesota 55455, United States

Eyesight Ophthalmic Services, PA, Portsmouth, New Hampshire 03801, United States

Eye Care for the Adirondacks, Plattsburgh, New York 12901, United States

Retina-Vitreous Surgeons of Central New York, PC, Syracuse, New York 13224, United States

Charlotte Eye Ear Nose and Throat Assoc, PA, Charlotte, North Carolina 28210, United States

Retina Associates of Cleveland, Inc., Beachwood, Ohio 44122, United States

Retina Northwest, PC, Portland, Oregon 97210, United States

Family Eye Group, Lancaster, Pennsylvania 17601-2644, United States

Southeastern Retina Associates, PC, Kingsport, Tennessee 37660, United States

Southeastern Retina Associates, P.C., Knoxville, Tennessee 37909, United States

Texas Retina Associates, Lubbock, Texas 79424, United States

Retinal Consultants of San Antonio, San Antonio, Texas 78240, United States

University of Washington Medical Center, Seattle, Washington 98195, United States

Medical College of Wisconsin, Milwaukee, Wisconsin 53226, United States

Additional Information

Starting date: May 2011
Last updated: January 9, 2015

Page last updated: August 23, 2015

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