Dextromethorphan for Diabetic Macular Edema
- Many people with diabetes have macular edema (swelling) at the back of the eye. Macular edema can cause loss of vision. Studies suggest that inflammation may be involved in the swelling. A drug called dextromethorphan may help prevent the inflammation and the swelling. Dextromethorphan is approved for use as a cough medicine, but it has not been studied to see if it can help in diabetic macular edema.
- To see if dextromethorphan can help treat diabetic macular edema.
- Individuals at least 18 years of age who have diabetic macular edema in at least one eye.
- This study lasts 2 years, and will require at least 14 visits to the National Eye Institute outpatient clinic. Study visits will be every month for the first 2 months and then every other month. Each visit will take about 2 to 4 hours.
- Participants will be screened with a physical exam, medical history, eye exam, and blood tests. One eye with macular edema will be chosen as the study eye for testing.
- Participants will take dextromethorphan twice a day, about 12 hours apart, for 2 years. A study diary will help keep track of the date, time, and number of pills taken.
- Participants will have study visits once a month for the first 2 months and then every other month for the rest of the study. Each study visit will involve eye exams and blood and urine tests.
- Four months after starting the study medication, participants may have laser surgery or other treatments for the macular edema, if it is needed.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot Phase I/II Study for the Evaluation of Dextromethorphan as a Microglia Inhibitor in the Treatment of Diabetic Macular Edema (MiDME2)|
- The primary outcome is the change in retinal thickness as measured by OCT at six months compared to baseline [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
- The change in retinal thickness at 6, 12, 18 and 24 months [ Time Frame: 6, 12, 18 and 24 months ] [ Designated as safety issue: Yes ]
- Change in BCVA at 12, 18 and 24 months [ Time Frame: 2, 18 and 24 months ] [ Designated as safety issue: Yes ]
- Changes in fluid leakage in the macula at 6, 12, 18 and 24 months compared to baseline [ Time Frame: 6, 12, 18 and 24 months ] [ Designated as safety issue: No ]
- Ocular toxicity and adverse events [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||August 2011|
|Estimated Study Completion Date:||December 2015|
|Primary Completion Date:||June 2014 (Final data collection date for primary outcome measure)|
Diabetic retinopathy (DR) is one of the leading causes of blindness in the United States. A frequent manifestation of DR is diabetic macular edema (DME) for which the only proven treatment is laser photocoagulation. In the retina, microglia are capable of migrating through the retina to sites of inflammation to associate closely with neurons and the vasculature, and are key cellular players in the mediation of processes of chronic inflammation implicated in DME. For these reasons, microglia represent a promising cellular target for forms of therapy that limit the deleterious inflammatory changes found in DR. The objective of this study is to investigate the safety and efficacy of dextromethorphan as a microglia inhibitor in participants with DME.
Eligibility criteria include presence of diabetic retinopathy with retinal thickening due to diabetic macular edema within 3000 m of the center of the macula as measured by optical coherence tomography (OCT) , and visual acuity better than 20/200 in the study eye.
Five participants will be initially enrolled in this unmasked pilot study. However, up to an additional three participants may be enrolled to account for participants who withdraw from the study prior to receipt of six months of study treatment. Participants will take an oral dose of 60 mg of dextromethorphan twice daily for 24 months. During each visit, participants will have their visual acuity measured and will undergo OCT testing to measure retinal thickness. Beginning at the Month 4 visit, participants will be assessed for worsening disease defined as loss of greater than or equal to 15 ETDRS letters of vision compared to baseline or a greater than or equal to 50% increase in total central retinal thickness as measured by OCT. Additionally, beginning at the Month 6 visit, participants will be eligible for treatment, with either focal laser or anti-VEGF injections (such as bevacizumab or ranibizumab) if they have center-involving macular edema.
The primary outcome is the change in retinal thickness measured by OCT at 6 months compared to baseline. Secondary outcomes include the change in retinal thickness as measured by OCT at 12, 18 and 24 months compared to baseline, change in best-corrected visual acuity (BCVA) at 6, 12, 18 and 24 months compared to baseline, change in mean macular sensitivity as measured by microperimetry at 6, 12, 18 and 24 months compared to baseline, as well as changes in fluid leakage in the macula as demonstrated by fluorescein angiography at 6, 12, 18 and 24 months compared to baseline. Safety outcomes include the number and severity of systemic and ocular toxicities, and adverse events.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01441102
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Catherine A Cukras, M.D.||National Eye Institute (NEI)|