Minocycline to Treat Branch Retinal Vein Occlusion
- Conditions
- Retinal Vein Occlusion
- Interventions
- Registration Number
- NCT01468831
- Lead Sponsor
- National Eye Institute (NEI)
- Brief Summary
Background:
- 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.
Objectives:
- To test the safety and effectiveness of minocycline as a treatment for branch retinal vein occlusion.
Eligibility:
- 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.
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.
* 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.
- Detailed Description
Objective:
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 occlusion (BRVO).
Study Population:
A minimum of ten 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 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.
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, 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 9
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Participants injected with bevacizumab for three months followed by PRN dosing and placebo twice daily for 24 months Placebo Bevacizumab Participants injected with bevacizumab for three months followed by PRN dosing and placebo twice daily for 24 months Minocycline Minocycline Participants injected with bevacizumab for three months followed by PRN dosing and 100mg minocycline twice daily for 24 months Minocycline Bevacizumab Participants injected with bevacizumab for three months followed by PRN dosing and 100mg minocycline twice daily for 24 months
- Primary Outcome Measures
Name Time Method Mean Change in Best-corrected Visual Acuity (BCVA) in the Study Eye at 12 Months Compared to Baseline. Baseline to Month 12 The primary outcome measure is the mean difference between the minocycline and placebo groups in the change in best-corrected visual acuity (BCVA), as measured in ETDRS letters, in the study eye at 12 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 12 months.
- Secondary Outcome Measures
Name Time Method Number of Bevacizumab Injections From Baseline to 12 Months Baseline to Month 12 The outcome measure is the difference between the minocycline and placebo groups in the number of bevacizumab injections administered to participants between baseline and 12 months.
Number of Bevacizumab Injections From Baseline to 24 Months Baseline to Month 24 The outcome measure is the difference between the minocycline and placebo groups in the number of bevacizumab injections administered to participants between baseline and 24 months.
Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 3 Months Compared to Baseline Baseline to Month 3 The outcome measure is the mean difference between the minocycline and placebo groups in the change in macular sensitivity as measured by microperimetry in the study eye at 3 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 3 months. Higher macular sensitivity (higher db) is better.
Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 6 Months Compared to Baseline Baseline to Month 6 The outcome measure is the mean difference between the minocycline and placebo groups in the change in macular sensitivity as measured by microperimetry in the study eye at 6 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 6 months. Higher macular sensitivity (higher db) is better.
Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 12 Months Compared to Baseline Baseline to Month 12 The outcome measure is the mean difference between the minocycline and placebo groups in the change in macular sensitivity as measured by microperimetry in the study eye at 12 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 12 months. Higher macular sensitivity (higher db) is better.
Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 18 Months Compared to Baseline Baseline to Month 18 The outcome measure is the mean difference between the minocycline and placebo groups in the change in macular sensitivity as measured by microperimetry in the study eye at 18 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 18 months. Higher macular sensitivity (higher db) is better.
Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 24 Months Compared to Baseline Baseline to Month 24 The outcome measure is the mean difference between the minocycline and placebo groups in the change in macular sensitivity as measured by microperimetry in the study eye at 24 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 24 months. Higher macular sensitivity (higher db) is better.
Changes in Retinal Thickness in the Study Eye as Measured by Optical Coherence Tomography (OCT) at 18 Months Compared to Baseline Baseline to Month 18 The outcome measure is the mean difference between the minocycline and placebo groups in the change in central retinal thickness in the study eye at 18 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 18 months.
Changes in Retinal Thickness in the Study Eye as Measured by Optical Coherence Tomography (OCT) at 24 Months Compared to Baseline Baseline to Month 24 The outcome measure is the mean difference between the minocycline and placebo groups in the change in central retinal thickness in the study eye at 24 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 24 months.
Number of Participants Improving ≥ 1 logOCT Scale Step in the Study Eye at 24 Months Compared to Baseline Baseline to Month 24 The outcome measure is the difference between the minocycline and placebo groups in the number of participants experiencing an improvement of ≥ 1 logOCT scale step from baseline to Month 24. Improvement in ≥ 1 logOCT scale step is defined as a decrease of ≥ 1-step on the logOCT scale. A 1-step decrease is equivalent to at least a 20% improvement of central macular thickness.
Mean Change in the ETDRS BCVA in the Study Eye at 24 Months Compared to Baseline Baseline to Month 24 The outcome measure is the mean difference between the minocycline and placebo groups in the change in best-corrected visual acuity (BCVA), as measured in ETDRS letters, in the study eye at 24 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 24 months.
Changes in Retinal Thickness in the Study Eye as Measured by Optical Coherence Tomography (OCT) at 6 Months Compared to Baseline Baseline to Month 6 The outcome measure is the mean difference between the minocycline and placebo groups in the change in central retinal thickness in the study eye at 6 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 6 months.
Changes in Retinal Thickness in the Study Eye as Measured by Optical Coherence Tomography (OCT) at 12 Months Compared to Baseline Baseline to Month 12 The outcome measure is the mean difference between the minocycline and placebo groups in the change in central retinal thickness in the study eye at 12 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 12 months.
Number of Participants Improving ≥ 1 logOCT Scale Step in the Study Eye at 12 Months Compared to Baseline Baseline to Month 12 The outcome measure is the difference between the minocycline and placebo groups in the number of participants experiencing an improvement of ≥ 1 logOCT scale step from baseline to Month 12. Improvement in ≥ 1 logOCT scale step is defined as a decrease of ≥ 1-step on the logOCT scale. A 1-step decrease is equivalent to at least a 20% improvement of central macular thickness.
Number of Participants Experiencing Changes in Fluid Leakage in the Macula of the Study Eye as Demonstrated by Fluorescein Angiography at 12 Months Compared to Baseline Baseline to Month 12 The outcome measure is the difference between the between the minocycline and placebo groups in the number of participants experiencing changes in fluid leakage in the macula of the study eye as demonstrated by fluorescein angiography at 12 months compared to baseline. The counts presented are the number of participants experiencing decrease, increase, or no change in fluid leakage from baseline.
Number of Participants Experiencing Changes in Fluid Leakage in the Macula of the Study Eye as Demonstrated by Fluorescein Angiography at 24 Months Compared to Baseline. Baseline to Month 24 The outcome measure is the difference between the between the minocycline and placebo groups in the number of participants experiencing changes in fluid leakage in the macula of the study eye as demonstrated by fluorescein angiography at 24 months compared to baseline. The counts presented are the number of participants experiencing decrease, increase, or no change in fluid leakage from baseline.
Trial Locations
- Locations (2)
National Institutes of Health Clinical Center, 9000 Rockville Pike
🇺🇸Bethesda, Maryland, United States
Bristol Eye Hospital
🇬🇧Bristol, United Kingdom