Minocycline to Treat Branch Retinal Vein Occlusion
- Branch retinal vein occlusion (BRVO) is a blockage of the small veins that carry blood away from the retina in the back of the eye. It often leads to macular edema, a swelling of the retina that is a common source of vision loss. Studies suggest that inflammation might be a cause. Minocycline is a drug that might help prevent cells involved in inflammation from becoming activated. It is approved for use as an antibiotic, but it has not yet been tested to see if it can treat BRVO.
- To test the safety and effectiveness of minocycline as a treatment for branch retinal vein occlusion.
- Individuals at least 18 years of age who have branch retinal vein occlusion in at least one eye, with vision between 20/32 and 20/200.
- This study lasts 2 years, with at least 25 visits to the National Eye Institute. Participants must agree to protect themselves from sunlight or artificial ultraviolet rays while in this study.
- Participants will be screened with a physical exam and medical history. They will also have blood tests and an eye exam. One eye will be selected as the study eye to receive the medicine.
- Those in the study will take minocycline or a placebo pill twice a day, about 12 hours apart, for 2 years.
- Participants will have monthly visits for blood tests and full eye exams to study the effect of the treatment. Other exams may include thyroid tests and eye imaging studies. Those in the study may also receive injections of a drug to prevent the growth of new blood vessels in the eye.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||A Pilot Study for the Evaluation of Minocycline as a Microglia Inhibitor in the Treatment of Branch Retinal Vein Occlusions|
- The primary outcome is the comparison between the minocycline and placebo groups of the mean change in best-corrected visual acuity (BCVA) in the study eye at 12 months compared to baseline. [ Time Frame: ag 6 months ] [ Designated as safety issue: Yes ]
- Number of intravitreal bevacizumab injections in the minocycline group vs. placebo. [ Time Frame: 6, 12, 18, 24 months ] [ Designated as safety issue: Yes ]
- Change in retinal thickness as measured by OCT at 6, 12, 18 and 24 months vs. baseline. [ Time Frame: 6, 12, 18, and 24 months ] [ Designated as safety issue: Yes ]
- Change in BCVA at 24 months vs. baseline. [ Time Frame: 6, 12, 18, 24 months ] [ Designated as safety issue: Yes ]
|Study Start Date:||September 2011|
|Estimated Study Completion Date:||January 2017|
|Estimated Primary Completion Date:||January 2017 (Final data collection date for primary outcome measure)|
Retinal vein occlusions (RVO) are significant sources of vision loss, affecting mostly healthy people over 55 years of age. The common source of vision loss is the macular edema accompanying the retinal injury. Very recently, studies employing monthly anti-vascular endothelial growth factor (VEGF) treatments have demonstrated a benefit to this line of treatment; however, the duration of effectiveness appears to be short lived and the length of time needed for these monthly injections remains unknown. A histologic study of human retinas with RVOs found the presence of activated microglia. 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. For these reasons, microglia represent a promising cellular target for forms of therapy that limit the deleterious inflammatory changes found in vein occlusions. Minocycline, a second-generation tetracycline, has been shown to exhibit anti-inflammatory properties, including microglia inhibition. The objective of this study is to investigate the safety and efficacy of minocycline as a microglia inhibitor in participants with branch retinal vein occlusions (BRVO).
Ten participants will be initially accrued; however, up to 20 participants who meet the eligibility criteria may be enrolled in anticipation of participant withdrawal. Eligibility criteria include: foveal center-involved macular edema secondary to a BRVO, retinal thickness in the central subfield greater than 350 microns as measured by optical coherence tomography (OCT) and visual acuity (VA) between 20/32 and 20/200 in the study eye.
In this pilot, double-masked, randomized, single center study, participants will receive monthly bevacizumab injections for the first three months, followed by PRN dosing. In addition, participants will take an oral dose of 100 mg of minocycline or placebo twice daily for 24 months. During each monthly visit, participants will have their visual acuity measured and will undergo OCT testing to measure retinal thickness. At the Month 3 visit and thereafter, participants will be evaluated for "improvement" and "worsening" and will be eligible for additional bevacizumab treatment and/or investigational product depending on which criteria they fulfill. Additionally, at Month 12, participants will also be evaluated for no improvement.
The primary outcome is the difference in mean change in best-corrected visual acuity (BCVA), as measured in ETDRS letters, between the minocycline and placebo groups in the study eye at 12 months compared to baseline. Secondary outcomes include the difference between the minocycline and placebo groups in the number of intravitreal bevacizumab injections between 12 and 24 months and baseline, the mean change in BCVA at 24 months compared to baseline, the changes in retinal thickness as measured by OCT at 6, 12, 18 and 24 months compared to baseline, number of participants improving greater than or equal to 1 logOCT scale step at 12 and 24 months compared to baseline, as well as changes in fluid leakage in the macula as demonstrated by fluorescein angiography at 12 and 24 months compared to baseline. Safety outcomes include the number of participant withdrawals, the number and severity of systemic and ocular toxicities and the number of adverse events.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01468831
|Contact: Meg (Margaret) E Gordon, R.N.||(301) email@example.com|
|Contact: Catherine A Cukras, M.D.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||Catherine A Cukras, M.D.||National Eye Institute (NEI)|