This study is NOT currently recruiting participants.
Number
11-EI-0263
Sponsoring Institute
National Eye Institute (NEI)
Recruitment Detail
Type: Completed Study; data analyses ongoing Gender: Male & Female Min Age: 18 Years Max Age: 120 Years
Referral Letter Required
No
Population Exclusion(s)
Children;Pregnant Women
Keywords
Eye Disease; Macular Edema
Recruitment Keyword(s)
None
Condition(s)
Retinal Vein Occlusion
Investigational Drug(s)
Minocycline
Investigational Device(s)
Intervention(s)
Drug: Minocycline Drug: Placebo Drug: Bevacizumab
Supporting Site
National Eye Institute
- 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.
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INCLUSION CRITERIA: To be eligible, the following inclusion criteria must be met, where applicable: -Participant is 18 years of age or older. -Participant must understand and sign the protocol s informed consent document. -Female participants of childbearing potential must not be pregnant or breast-feeding and must be willing to undergo serum (BRC sites only) and urine pregnancy tests throughout the study. -For the NEI Site: Female participants of childbearing potential and male participants able to father children must have (or have a partner who has) had a hysterectomy or vasectomy, be completely abstinent from intercourse or must agree to practice two acceptable methods of contraception throughout the course of the study and for one week after study medication discontinuation (based on the half life of minocycline which is 11-22 hours). Acceptable methods of contraception include: --hormonal contraception (i.e., birth control pills, injected hormones, dermal patch or vaginal ring), --intrauterine device, --barrier methods (diaphragm, condom) with spermicide, or --surgical sterilization (hysterectomy or tubal ligation). Oral birth control pills must be used with caution as minocycline decreases the effectiveness of some oral contraceptives. Participants already taking oral contraceptives may continue to use them, but must agree to use at least one other method of birth control while on study. For the BRC Sites: Female participants of childbearing potential and male participants able to father children must have (or have a partner who has) had a hysterectomy or vasectomy, or be completely abstinent from intercourse. Male participants or male partners (of female participants) who have not had a vasectomy or are not abstinent are required to use a condom with spermicide throughout the course of the study and for one week after study medication discontinuation (based on the half life of minocycline which is 11-22 hours). Female participants of childbearing potential or female partners (of male participants) of childbearing potential must practice one of the below acceptable methods of contraception throughout the course of the study and for one week after study medication discontinuation: a. hormonal contraception (i.e., birth control pills*, injected hormones, dermal patch or vaginal ring), b. intrauterine device, c. barrier methods (e.g., diaphragm) with spermicide, or d. surgical sterilization (hysterectomy or tubal ligation). Abstinence is only acceptable when it is the participant s preferred and usual lifestyle choice. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Oral birth control pills must be used with caution as minocycline decreases the effectiveness of some oral contraceptives. Participants already taking oral contraceptives may continue to use them, but must agree to use at least one other method of birth control while on study. It should be noted that two forms of contraception (as specified above) will be used by sexually active participants for the duration of the study and for one week after study medication discontinuation. -Participants must agree to notify the study investigator or coordinator if any of their doctors initiate a new medication during the course of the study. -Participant must have normal renal function and liver function or have mild abnormalities not above grade 1 as defined by the Common Terminology Criteria for Adverse Events v4.0 (CTCAE). -Participant must agree to minimize exposure to sunlight or artificial UV rays and to wear protective clothing, sunglasses and sunscreen (minimum SPF 15) if s/he must be out in the sun. -Participant has at least one eye that meets the study eye criteria listed in Section 3.2. EXCLUSION CRITERIA: A participant is not eligible if any of the following exclusion criteria are present: -Participant is in another investigational study and actively receiving investigational product for BRVO. -Participant is unable to comply with study procedures or follow-up visits. -Participant has a known hypersensitivity to sodium fluorescein dye. -Participant has a condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure and glycemic control). -Participant has a history of chronic renal failure requiring dialysis or kidney transplant. -Participant has a history of chronic hepatitis or liver failure. -Participant has an allergy or hypersensitivity to minocycline or any drug in the tetracycline family. -Participant is currently taking a tetracycline medication. -Participant is taking any medication that could adversely interact with minocycline such as methoxyflurane. -Participant has a blood pressure of greater than 180/110 (systolic above 180 OR diastolic above 110). If blood pressure is brought below 180/110 by anti-hypertensive treatment, the participant can become eligible. -Participant is currently being treated with systemic anti-VEGF agents or systemic steroids. -Participant had a cerebral vascular event (CVA) or myocardial infarction (MI) within three months prior to study entry. -Participant has a history of thyroid cancer. Study Eye Eligibility Criteria: -The participant must have at least one eye meeting all inclusion criteria and none of the exclusion criteria listed below: --Study Eye Inclusion Criteria: ---The study eye has a best-corrected ETDRS visual acuity score between 78 and 34 letters (i.e., between 20/32 and 20/200). ---The study eye shows evidence of definite retinal thickening due to a BRVO based on clinical examination involving the center of the macula that is not refractory to further therapy as based on the investigator s clinical judgment. BRVO is defined as an eye that had retinal hemorrhage or other biomicroscopic evidence of RVO (e.g., telangiectatic capillary bed) and a dilated (or previously dilated) venous system in one or two quadrants or less of the retina drained by the affected vein. Hemiretinal vein occlusion (HRVO) is an RVO that involves two altitudinal quadrants. In this study, eyes with a HRVO will be considered a BRVO and are given the same treatment as BRVO eyes. ---The study eye has retinal thickness in the central subfield on baseline OCT measurement >350 microns, as measured by Zeiss Cirrus spectral domain OCT, or an equivalent retinal thickness on a similar OCT machine. ---The study eye has media clarity and pupillary dilation sufficient for adequate fundus photographs. Furthermore, the participant must be able to cooperate during the procedure for accurate fundus photographs. --Study Eye Exclusion Criteria: ---The study eye has macular edema considered to be due to a cause other than BRVO. ---An eye should not be considered eligible if: ----The macular edema is considered to be related to cataract extraction, or ----Clinical examination and/or OCT suggest that vitreoretinal interface disease (e.g., a taut posterior hyaloid or epiretinal membrane) is the primary cause of the macular edema, or ----Clinical examination, medical history and/or fluorescein angiography suggest that diabetic retinopathy is the primary cause of the edema. ----The study eye has a history of a recurrent RVO. ----The study eye has a history of RVO present for > 18 months. ----A brisk afferent pupillary defect (APD) is present in the study eye. ----An ocular condition is present in the study eye such that, in the opinion of the investigator, visual acuity would not improve from resolution of macular edema (e.g., foveal atrophy, pigmentary changes, dense subfoveal hard exudates, laser scar at fovea, non-retinal condition). ----An ocular condition (other than RVO) is present that, in the opinion of the investigator, might affect macular edema or alter visual acuity during the course of the study (e.g., uveitis or other ocular inflammatory disease, neovascular glaucoma, Irvine-Gass Syndrome, etc.). ----A substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by three lines or more (i.e., cataract would be reducing acuity to 20/40 or worse if eye was otherwise normal) is present in the study eye. ----The study eye has had panretinal or sectoral scatter photocoagulation (PRP) within four months prior to study entry. ----The study eye has had pars plana vitrectomy within six months prior to study entry. ----The study eye has undergone major ocular surgery (including cataract extraction, scleral buckle, any intraocular surgery, etc.) within three months prior to study entry. ----A yttrium aluminum garnet (YAG) capsulotomy has been performed on the study eye within two months prior to study entry. ----The study eye has had treatment < 3 months prior to study entry of intravitreal or periocular steroid injections. ----The study eye has had treatment < 28 days prior to study entry of intravitreal anti-VEGF agents. Study Eye Selection Criteria in Cases of Bilateral Disease: If both eyes of a participant meet the criteria, the study eye will be determined at the investigator's discretion.
To be eligible, the following inclusion criteria must be met, where applicable:
-Participant is 18 years of age or older.
-Participant must understand and sign the protocol s informed consent document.
-Female participants of childbearing potential must not be pregnant or breast-feeding and must be willing to undergo serum (BRC sites only) and urine pregnancy tests throughout the study.
-For the NEI Site: Female participants of childbearing potential and male participants able to father children must have (or have a partner who has) had a hysterectomy or vasectomy, be completely abstinent from intercourse or must agree to practice two acceptable methods of contraception throughout the course of the study and for one week after study medication discontinuation (based on the half life of minocycline which is 11-22 hours). Acceptable methods of contraception include:
--hormonal contraception (i.e., birth control pills, injected hormones, dermal patch or vaginal ring),
--intrauterine device,
--barrier methods (diaphragm, condom) with spermicide, or
--surgical sterilization (hysterectomy or tubal ligation).
Oral birth control pills must be used with caution as minocycline decreases the effectiveness of some oral contraceptives. Participants already taking oral contraceptives may continue to use them, but must agree to use at least one other method of birth control while on study.
For the BRC Sites: Female participants of childbearing potential and male participants able to father children must have (or have a partner who has) had a hysterectomy or vasectomy, or be completely abstinent from intercourse.
Male participants or male partners (of female participants) who have not had a vasectomy or are not abstinent are required to use a condom with spermicide throughout the course of the study and for one week after study medication discontinuation (based on the half life of minocycline which is 11-22 hours). Female participants of childbearing potential or female partners (of male participants) of childbearing potential must practice one of the below acceptable methods of contraception throughout the course of the study and for one week after study medication discontinuation:
a. hormonal contraception (i.e., birth control pills*, injected hormones, dermal patch or vaginal ring),
b. intrauterine device,
c. barrier methods (e.g., diaphragm) with spermicide, or
d. surgical sterilization (hysterectomy or tubal ligation).
Abstinence is only acceptable when it is the participant s preferred and usual lifestyle choice. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
It should be noted that two forms of contraception (as specified above) will be used by sexually active participants for the duration of the study and for one week after study medication discontinuation.
-Participants must agree to notify the study investigator or coordinator if any of their doctors initiate a new medication during the course of the study.
-Participant must have normal renal function and liver function or have mild abnormalities not above grade 1 as defined by the Common Terminology Criteria for Adverse Events v4.0 (CTCAE).
-Participant must agree to minimize exposure to sunlight or artificial UV rays and to wear protective clothing, sunglasses and sunscreen (minimum SPF 15) if s/he must be out in the sun.
-Participant has at least one eye that meets the study eye criteria listed in Section 3.2.
EXCLUSION CRITERIA:
A participant is not eligible if any of the following exclusion criteria are present:
-Participant is in another investigational study and actively receiving investigational product for BRVO.
-Participant is unable to comply with study procedures or follow-up visits.
-Participant has a known hypersensitivity to sodium fluorescein dye.
-Participant has a condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure and glycemic control).
-Participant has a history of chronic renal failure requiring dialysis or kidney transplant.
-Participant has a history of chronic hepatitis or liver failure.
-Participant has an allergy or hypersensitivity to minocycline or any drug in the tetracycline family.
-Participant is currently taking a tetracycline medication.
-Participant is taking any medication that could adversely interact with minocycline such as methoxyflurane.
-Participant has a blood pressure of greater than 180/110 (systolic above 180 OR diastolic above 110).
If blood pressure is brought below 180/110 by anti-hypertensive treatment, the participant can become eligible.
-Participant is currently being treated with systemic anti-VEGF agents or systemic steroids.
-Participant had a cerebral vascular event (CVA) or myocardial infarction (MI) within three months prior to study entry.
-Participant has a history of thyroid cancer.
Study Eye Eligibility Criteria:
-The participant must have at least one eye meeting all inclusion criteria and none of the exclusion criteria listed below:
--Study Eye Inclusion Criteria:
---The study eye has a best-corrected ETDRS visual acuity score between 78 and 34 letters (i.e., between 20/32 and 20/200).
---The study eye shows evidence of definite retinal thickening due to a BRVO based on clinical examination involving the center of the macula that is not refractory to further therapy as based on the investigator s clinical judgment. BRVO is defined as an eye that had retinal hemorrhage or other biomicroscopic evidence of RVO (e.g., telangiectatic capillary bed) and a dilated (or previously dilated) venous system in one or two quadrants or less of the retina drained by the affected vein. Hemiretinal vein occlusion (HRVO) is an RVO that involves two altitudinal quadrants. In this study, eyes with a HRVO will be considered a BRVO and are given the same treatment as BRVO eyes.
---The study eye has retinal thickness in the central subfield on baseline OCT measurement >350 microns, as measured by Zeiss Cirrus spectral domain OCT, or an equivalent retinal thickness on a similar OCT machine.
---The study eye has media clarity and pupillary dilation sufficient for adequate fundus photographs. Furthermore, the participant must be able to cooperate during the procedure for accurate fundus photographs.
--Study Eye Exclusion Criteria:
---The study eye has macular edema considered to be due to a cause other than BRVO.
---An eye should not be considered eligible if:
----The macular edema is considered to be related to cataract extraction, or
----Clinical examination and/or OCT suggest that vitreoretinal interface disease (e.g., a taut posterior hyaloid or epiretinal membrane) is the primary cause of the macular edema, or
----Clinical examination, medical history and/or fluorescein angiography suggest that diabetic retinopathy is the primary cause of the edema.
----The study eye has a history of a recurrent RVO.
----The study eye has a history of RVO present for > 18 months.
----A brisk afferent pupillary defect (APD) is present in the study eye.
----An ocular condition is present in the study eye such that, in the opinion of the investigator, visual acuity would not improve from resolution of macular edema
(e.g., foveal atrophy, pigmentary changes, dense subfoveal hard exudates, laser scar at fovea, non-retinal condition).
----An ocular condition (other than RVO) is present that, in the opinion of the investigator, might affect macular edema or alter visual acuity during the course of the study
(e.g., uveitis or other ocular inflammatory disease, neovascular glaucoma, Irvine-Gass Syndrome, etc.).
----A substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by three lines or more (i.e., cataract would be reducing acuity to 20/40 or worse if eye was otherwise normal) is present in the study eye.
----The study eye has had panretinal or sectoral scatter photocoagulation (PRP) within four months prior to study entry.
----The study eye has had pars plana vitrectomy within six months prior to study entry.
----The study eye has undergone major ocular surgery (including cataract extraction, scleral buckle, any intraocular surgery, etc.) within three months prior to study entry.
----A yttrium aluminum garnet (YAG) capsulotomy has been performed on the study eye within two months prior to study entry.
----The study eye has had treatment < 3 months prior to study entry of intravitreal or periocular steroid injections.
----The study eye has had treatment < 28 days prior to study entry of intravitreal anti-VEGF agents.
Study Eye Selection Criteria in Cases of Bilateral Disease:
If both eyes of a participant meet the criteria, the study eye will be determined at the investigator's discretion.
Principal Investigator
Referral Contact
For more information: