Minocycline to Treat Central Retinal Vein Occlusion

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Eye Institute (NEI) )
ClinicalTrials.gov Identifier:
NCT01468844
First received: October 8, 2011
Last updated: June 25, 2014
Last verified: May 2014
  Purpose

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 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.
  • 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....

Condition Intervention Phase
Retinal Vein Occlusion
Drug: Minocycline
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Pilot Study for the Evaluation of Minocycline as a Microglia Inhibitor in the Treatment of Central Retinal Vein Occlusions

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • 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 of the eye at 12 months compared to baseline. [ Time Frame: ag 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Secondary outcomes include the number of intravitreal bevacizumab injections in the minocycline group vs. placebo, change in retinal thickness as measured by OCT at 6, 12, 18 and 24 months vs. baseline, and change in BCVA at 24 months vs. baseli... [ Time Frame: 6, 12, 18 and 24 months ] [ Designated as safety issue: Yes ]
  • Safety outcomes include the number of participant withdrawals, the number and severity of systemic and ocular toxicities and the number of adverse events. [ Time Frame: 6, 12, 18 and 24 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 20
Study Start Date: September 2011
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Minocycline
    N/A
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:

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 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 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 fufill. 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, 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 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

To be eligible, the following participant-level 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 urine pregnancy tests throughout the study.
  • 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 life of minocycline 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.

  • Participants must agree to notify the study investigator or coordinator if any of their doctors initiate a new medication during the course of this 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 below.

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 CRVOs.
  • 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 > 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 steroids.
  • Participant had a cerebral vascular event (CVA) or myocardial infarction (MI) within three months prior study entry.
  • Participant has a history of thyroid cancer.

STUDY ELE 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 definite retinal thickening due to a CRVO 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. CRVO 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 at least three quadrants of the retina drained by the affected vein.
  • 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:

  • Macular edema is considered to be due to a cause other than CRVO.

    --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
    • 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 (other than RVO) is present 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., vein occlusion, 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01468844

Contacts
Contact: Meg (Margaret) E Gordon, R.N. (301) 435-1833 meg.gordon@nih.gov
Contact: Catherine A Cukras, M.D. (301) 435-5061 cukrasc@mail.nih.gov

Locations
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    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Catherine A Cukras, M.D. National Eye Institute (NEI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Eye Institute (NEI) )
ClinicalTrials.gov Identifier: NCT01468844     History of Changes
Other Study ID Numbers: 110264, 11-EI-0264
Study First Received: October 8, 2011
Last Updated: June 25, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Central Retinal Vein Occlusion
Minocycline
Retinal Vein Occlusion
CRVO

Additional relevant MeSH terms:
Retinal Vein Occlusion
Retinal Diseases
Eye Diseases
Venous Thrombosis
Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Minocycline
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014