Diabetic Macular EdemaPhase 2NCT01331005
NSAID Phase II for Non-central Involved Diabetic Macular Edema (DME)
A Phase 2 study testing nepafenac 0.1% drops in people with Diabetic Macular Edema, run by Jaeb Center for Health Research at 32 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Macular Edema
- What is being tested?
- nepafenac 0.1% drops
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 125 participants
- Where
- 32 sitesUnited States
- Study dates
- May 2011to Dec 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
32 sites in 1 country.
32 sites in 1 country
United States32 sites
Southeast Retina Center, P.C.
Augusta, Georgia, 30909
Elman Retina Group, P.A.
Baltimore, Maryland, 21237
Retina Associates of Cleveland, Inc.
Beachwood, Ohio, 44122
Joslin Diabetes Center
Boston, Massachusetts, 02215
Charlotte Eye Ear Nose and Throat Assoc, PA
Charlotte, North Carolina, 28210
Henry Ford Health System, Dept of Ophthalmology and Eye Care Services
Detroit, Michigan, 48202
Retina Consultants of Southwest Florida
Fort Myers, Florida, 33912
Vitreo-Retinal Associates
Grand Rapids, Michigan, 49525
Retina Associates of Hawaii, Inc.
Honolulu, Hawaii, 96813
Raj K. Maturi, M.D., P.C.
Indianapolis, Indiana, 46290
Southeastern Retina Associates, PC
Kingsport, Tennessee, 37660
Southeastern Retina Associates, P.C.
Knoxville, Tennessee, 37909
Central Florida Retina Institute
Lakeland, Florida, 33805
Family Eye Group
Lancaster, Pennsylvania, 17601-2644
Retina and Vitreous Associates of Kentucky
Lexington, Kentucky, 40509-1802
Loma Linda University Health Care, Dept. of Ophthalmology
Loma Linda, California, 92354
Texas Retina Associates
Lubbock, Texas, 79424
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
University of Minnesota
Minneapolis, Minnesota, 55455
American Eye Institute
New Albany, Indiana, 47150
Paducah Retinal Center
Paducah, Kentucky, 42001
Southern California Desert Retina Consultants, MC
Palm Springs, California, 92262
Eye Care for the Adirondacks
Plattsburgh, New York, 12901
Retina Northwest, PC
Portland, Oregon, 97210
Eyesight Ophthalmic Services, PA
Portsmouth, New Hampshire, 03801
Retinal Consultants of San Antonio
San Antonio, Texas, 78240
California Retina Consultants
Santa Barbara, California, 93103
University of Washington Medical Center
Seattle, Washington, 98195
Retina-Vitreous Surgeons of Central New York, PC
Syracuse, New York, 13224
Bay Area Retina Associates
Walnut Creek, California, 94598
Wolfe Eye Clinic
West Des Moines, Iowa, 50266
Retinal Consultants of Southern California Medical Group, Inc.
Westlake Village, California, 91361
About this study
Official title: A Phase II Evaluation of Topical Non-steroidal Anti-inflammatories in Eyes With Non Central Involved Diabetic Macular Edema
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.
Read the 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.
- Conditions
- Diabetic Macular Edema
- Being tested
- nepafenac 0.1% drops, Nepafenac Vehicle
- Keywords
- Macular Edema, Non steroidal anti-inflammatories
- Medical subject headings
- Macular Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nepafenac 0.1% dropsDrug
One drop three times per day for one year
Nepafenac VehicleOther
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo will be given three times per day for one year Receives: Other: Nepafenac Vehicle |
| nepafenac 0.1% drops | Active comparator | Nepafenac drops will be given three times per day for one year Receives: Drug: nepafenac 0.1% drops |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Change in Optical Coherence Tomography Measure Retinal Volume, mm3
Measured: From Baseline to 12 months
Secondary outcomes (2)
Mean Change in Visual Acuity
Visual Acuity was measured with the Electronic Early Treatment Study (E-ETDRS) visual acuity test. Unit of measure is based on the E-ETDRS letter score scale, 0-97, where 0 = worst and 97 = best.
Measured: baseline to 12 months
Change in OCT Central Subfield Thickness
95% CI will be obtained in each treatment group and compared between treatment groups at 1 year. For eyes that have received treatment for DME before 1 year, visual acuity and OCT measurements obtained at time of failure will be used instead of measurements at 1 year.
Measured: baseline to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2011 (estimated)
- Study startMay 2011
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetic Macular EdemaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 125 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jaeb Center for Health Research
- Sponsor type
- University, hospital or other
- Collaborators
- National Eye Institute (NEI)
- Responsible party
- Sponsor
- Investigators
- Scott M Friedman, MD, Principal investigator, Florida Retina Consultants
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01331005
- Sponsor's protocol ID
- DRCR.net Protocol R
- Other IDs
- U10EY018817-03, U10EY014231-09
- Status last verified
- Feb 2025
- First submitted
- 6 Apr 2011
- Last updated
- 10 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Friedman SM, Almukhtar TH, Baker CW, Glassman AR, Elman MJ, Bressler NM, Maker MP, Jampol LM, Melia M; Diabetic Retinopathy Clinical Research Network. Topical nepafenec in eyes with noncentral diabetic macular edema. Retina. 2015 May;35(5):944-56. doi: 10.1097/IAE.0000000000000403.
PubMed 25602634
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Evaluation of Topical Non-steroidal Anti-inflammatories in Eyes With Non Central Involved Diabetic Macular Edema
- ClinicalTrials.gov ID
- NCT01331005
- Acronym / sponsor ID
- DRCR.net Protocol R
- Conditions
- Diabetic Macular Edema
- Keywords
- Macular Edema, Non steroidal anti-inflammatories
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 125 participants (actual)
- Lead sponsor
- Jaeb Center for Health ResearchUniversity, hospital or other
- Collaborators
- National Eye Institute (NEI)
- Study start
- May 2011
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 7 Apr 2011 (estimated)
- Results
- Posted 16 Jan 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: Nepafenac VehiclePlacebo will be given three times per day for one year |
| nepafenac 0.1% drops | Active comparator | Drug: nepafenac 0.1% dropsNepafenac drops will be given three times per day for one year |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- 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:
- 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:
- At least one eye meets the study eye criteria.
Key exclusion criteria (31 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| nepafenac 0.1% dropsOne drop three times per day for one year | Drug | nepafenac 0.1% drops |
| Nepafenac VehiclePlacebo | Other | Placebo |
Primary outcome
Mean Change in Optical Coherence Tomography Measure Retinal Volume, mm3
Time frame: From Baseline to 12 months
2 secondary outcomes
Mean Change in Visual Acuity
Time frame: baseline to 12 months
Change in OCT Central Subfield Thickness
Time frame: baseline to 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 25602634Friedman SM, Almukhtar TH, Baker CW, Glassman AR, Elman MJ, Bressler NM, Maker MP, Jampol LM, Melia M; Diabetic Retinopathy Clinical Research Network. Topical nepafenec in eyes with noncentral diabetic macular edema. Retina. 2015 May;35(5):944-56. doi: 10.1097/IAE.0000000000000403.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Scott M Friedman, MD principal investigator
Florida Retina Consultants
32 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing nepafenac 0.1% drops in people with Diabetic Macular Edema, run by Jaeb Center for Health Research at 32 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 28 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Jan 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Change in Optical Coherence Tomography Measure Retinal Volume, mm3 (time frame: From Baseline to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01331005, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2025.