NCT01468844

Minocycline to Treat Central Retinal Vein Occlusion

A Pilot Study for the Evaluation of Minocycline as a Microglia Inhibitor in the Treatment of Central Retinal Vein Occlusions

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 6 (actual)
• Sponsor: National Eye Institute (NEI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Background: \- Central retinal vein occlusion (CRVO) is a blockage of the main vein that carries blood away from the retina in the back of the eye. It can lead 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 CRVO. Objectives: \- To test the safety and effectiveness of minocycline as a treatment for central retinal vein occlusion. Eligibility: \- Individuals at least 18 years of age who have central retinal vein occlusion in at least one eye, with vision between 20/32 and 20/200. Design: * This study lasts 2 years, with at least 25 visits. * 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. * Participants 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.

Detailed description

Objective: Retinal vein occlusions (RVOs) 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 retinal vein occlusions 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 microglial inhibition. The objective of this study is to investigate the safety and potential efficacy of minocycline as a microglia inhibitor in participants with central retinal vein occlusion (CRVO). Study Population: A minimum of 10 and a maximum of 20 participants who meet the eligibility criteria may be enrolled. Eligibility criteria include: foveal center-involved macular edema secondary to a CRVO, retinal thickness in the central subfield \>350 microns as measured by optical coherence tomography (OCT); and visual acuity (VA) between 20/32 and 20/200 in the study eye. Design: In this pilot, double-masked, randomized multi-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 (IP) depending on which criteria they fulfill. Additionally, at Month 12, participants will also be evaluated for no improvement. Outcome Measures: 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, changes in mean macular sensitivity as measured by microperimetry at 3, 6, 12, 18 and 24 months compared to baseline, the mean change in BCVA at 24 months compared to baseline, 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 and 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, number and severity of systemic and ocular toxicities and the number of adverse events (AEs).

Conditions

• Retinal Vein Occlusion

Interventions

Type	Name	Description
DRUG	Minocycline	100 mg pink opaque capsule
DRUG	Placebo	Placebo
DRUG	Bevacizumab	1.25 mg bevacizumab injection

Timeline

• Start date: 2011-12-21
• Primary completion: 2015-03-04
• Completion: 2015-05-13
• First posted: 2011-11-10
• Last updated: 2021-03-17
• Results posted: 2021-03-17

Locations

2 sites across 2 countries: United States, United Kingdom

Regulatory

• FDA-regulated drug study