MiBRVO
Research type
Research Study
Full title
A Pilot Study for the Evaluation of Minocycline as a Microglia Inhibitor in the Treatment of Branch Retinal Vein Occlusions
IRAS ID
180937
Contact name
Catherine Cukras
Contact email
Sponsor organisation
The National Eye Institute
Eudract number
2017-001179-21
Clinicaltrials.gov Identifier
Duration of Study in the UK
3 years, 2 months, 1 days
Research summary
Summary of Research
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 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 occlusion.\n\nIn this pilot, double-masked, randomized, multi-center study, a minimum of 10 and a maximum of 20 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.”
Summary of Results
The study entitled “A Pilot Study for the Evaluation of Minocycline as a Microglia Inhibitor in the Treatment of Branch Retinal Vein Occlusions” was sponsored by the National Eye Institute, National Institutes of Health. The Sponsor would like to thank all participants who participated in the study. The study was conducted at two sites, the National Eye Institute (NEI) in the United States (US) and the Bristol Eye Hospital (BEH) in the United Kingdom (UK).
Branch retinal vein occlusions (BRVOs) are significant sources of vision loss affecting mostly healthy people over 55 years of age and human retinas with RVOs show the presence of activated microglia which are capable of migrating through the retina to sites of inflammation. As Minocycline is capable of blocking microglia, this study was conducted to investigate the safety and potential effectiveness of minocycline as a microglia inhibitor in participants with BRVO.
Overall, nine participants with BRVO joined the study, seven in the US and two in the UK. Six of the seven US participants completed the study, and one ended the study early. Both participants in the UK completed the study.
Participants received monthly bevacizumab injections for the first three months of the study, followed by pro re nata (PRN) dosing. In addition, participants took an oral dose of either placebo or minocycline 100mg capsule twice daily, once in the morning and once in the evening approximately 12 hours apart for 24 months. Participants were selected for either the minocycline or placebo group in a 1:1 manner. The study was considered ‘masked,’ as none of the participants, investigators, or trial Sponsor knew whether participants received minocycline or placebo until after the study’s conclusion.
The study looked at the difference in mean change of 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. The difference in visual acuity between the two treatment groups is calculated as the Minocycline group minus the Placebo group. The results from the study showed that while participants in the minocycline group showed a larger increase in BVCA as compared to the placebo group, it was not considered a significant increase.
Minocycline was not found to be a safety risk for participants, and all adverse reactions related to minocycline were expected in line with the product’s approved labeling.
More information on the study, including results, can be found at: https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbRehJ-2Fi4xyo44sEgJVCl5Bdj8o1FpylFwbn362DUDJ-2FzswGSL2MEAp-2BMTfQ0pG7MTzOGO1RorIXqoPa18UoSB457cE-2Fb3Bghb0bOomqmXbQeujml_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YKA93FXtyTsY3WHo8i9sVaKTC6o27a-2Fq-2BfIWBSwldYxIsOTojL185n-2BiNfMmMAky8kJM-2BNhQx74G3JV2XWpKN-2FDrVcwWkvSSI9INMVKrbM3lNQ82bV-2BxAkpKTMDSduB2J4NX1XtAR68rvyTtZYT-2BRsij7En2oEsFcy0uq0SfjBrKQ-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7C76163a5bb14343a8270a08daa17afeb4%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637999846879598339%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=yvMAhhTl6NlanWJ1K0azNkzoY95Uv%2BTtubx7N9Aq4KA%3D&reserved=0
REC name
South West - Central Bristol Research Ethics Committee
REC reference
17/SW/0201
Date of REC Opinion
16 Nov 2017
REC opinion
Further Information Favourable Opinion