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Retinal Vein OcclusionPhase 1/2NCT01468844

Minocycline to Treat Central Retinal Vein Occlusion

A Phase 1/2 study testing Minocycline and Bevacizumab in people with Retinal Vein Occlusion, run by National Eye Institute (NEI) at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Retinal Vein Occlusion
What is being tested?
Minocycline and Bevacizumab
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
6 participants
Where
2 sitesin 2 countries
Study dates
21 Dec 2011to 13 May 2015
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 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),
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  • 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:
  • hormonal contraception (i.e., birth control pills*, injected hormones, dermal patch or vaginal ring),
  • intrauterine device,
  • barrier methods (e.g., diaphragm) with spermicide, or
  • 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 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 AEs 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 the Study Eye Eligibility Criteria below.

Who cannot join

  • 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.
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  • 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 systemic 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 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 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 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 (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.
  • STUDY EYE SELECTION CRITERIA IN CASES OF BILATERAL DISEASE:
  • If both eyes of a participant meet the criteria described above, the study eye will be determined at the investigator's discretion.

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

United Kingdom1 site

  • Bristol Eye Hospital

    Bristol

Other trials in United Kingdom

About this study

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

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.
Read more

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.
Read the 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).

Being tested
Minocycline, Placebo, Bevacizumab
Keywords
Visual Acuity, Retinal Vein Occlusion, Central Retinal Vein Occlusion, CRVO
Medical subject headings
Retinal Vein Occlusion

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MinocyclineDrug

    100 mg pink opaque capsule

  • PlaceboDrug

    Placebo

  • BevacizumabDrug

    1.25 mg bevacizumab injection

Study groups in NCT01468844
Study groupRoleWhat they receive
MinocyclineExperimentalParticipants injected with bevacizumab for three months followed by PRN dosing and 100mg minocycline twice daily for 24 months
Receives: Drug: Minocycline; Drug: Bevacizumab
PlaceboPlacebo comparatorParticipants injected with bevacizumab for three months followed by PRN dosing and placebo twice daily for 24 months
Receives: Drug: Placebo; Drug: Bevacizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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 Eye at 12 Months Compared to Baseline.

    The primary outcome measure is the mean 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.

    Measured: Baseline to Month 12

Secondary outcomes (16)

  1. Number of Participants Improving ≥ 1 logOCT Scale Step in the Study Eye at 12 Months Compared to Baseline

    Improvement of ≥ 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.

    Measured: Baseline to Month 12

  2. Number of Participants Improving ≥ 1 logOCT Scale Step in the Study Eye at 24 Months Compared to Baseline

    Improvement of ≥ 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.

    Measured: Baseline to Month 24

  3. Number of Bevacizumab Injections From Baseline to 12 Months

    The outcome measure is the number of bevacizumab injections administered to participants between baseline and 12 months.

    Measured: Baseline to Month 12

  4. Number of Bevacizumab Injections From Baseline to 24 Months

    The outcome measure is the number of bevacizumab injections administered to participants between baseline and 24 months.

    Measured: Baseline to Month 24

  5. Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 3 Months Compared to Baseline

    The outcome measure is the mean change in macular sensitivity in the study eye at 3 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 3 months.

    Measured: Baseline to Month 3

  6. Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 6 Months Compared to Baseline

    The outcome measure is the mean change in macular sensitivity in the study eye at 6 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 6 months.

    Measured: Baseline to Month 6

  7. Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 12 Months Compared to Baseline

    The outcome measure is the mean change in macular sensitivity in the study eye at 12 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 12 months.

    Measured: Baseline to Month 12

  8. Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 18 Months Compared to Baseline

    The outcome measure is the mean change in macular sensitivity in the study eye at 18 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 18 months.

    Measured: Baseline to Month 18

  9. Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 24 Months Compared to Baseline

    The outcome measure is the mean change in macular sensitivity in the study eye at 24 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 24 months.

    Measured: Baseline to Month 24

  10. Mean Change in the ETDRS BCVA in the Study Eye at 24 Months Compared to Baseline

    The outcome measure is the mean 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.

    Measured: Baseline to Month 24

  11. Changes in Retinal Thickness in the Study Eye as Measured by Optical Coherence Tomography (OCT) at 6 Months Compared to Baseline

    The outcome measure is the mean 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.

    Measured: Baseline to Month 6

  12. Changes in Retinal Thickness in the Study Eye as Measured by Optical Coherence Tomography (OCT) at 12 Months Compared to Baseline

    The outcome measure is the mean 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.

    Measured: Baseline to Month 12

  13. Changes in Retinal Thickness in the Study Eye as Measured by Optical Coherence Tomography (OCT) at 18 Months Compared to Baseline

    The outcome measure is the difference in the mean 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.

    Measured: Baseline to Month 18

  14. Changes in Retinal Thickness in the Study Eye as Measured by Optical Coherence Tomography (OCT) at 24 Months Compared to Baseline

    The outcome measure is the mean 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.

    Measured: Baseline to Month 24

  15. Changes in Fluid Leakage in the Macula of the Study Eye as Demonstrated by Fluorescein Angiography at 12 Months Compared to Baseline

    The outcome measure is 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.

    Measured: Baseline to Month 12

  16. Changes in Fluid Leakage in the Macula of the Study Eye as Demonstrated by Fluorescein Angiography at 24 Months Compared to Baseline.

    The outcome measure is the 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.

    Measured: Baseline to Month 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Nov 2011 (estimated)
  2. Study start21 Dec 2011
  3. Primary completion4 Mar 2015
  4. Study completion13 May 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01468844
Sponsor's protocol ID
110264
Other IDs
11-EI-0264
Status last verified
Feb 2020
First submitted
8 Oct 2011
Last updated
17 Mar 2021
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Mitchell P, Smith W, Chang A. Prevalence and associations of retinal vein occlusion in Australia. The Blue Mountains Eye Study. Arch Ophthalmol. 1996 Oct;114(10):1243-7. doi: 10.1001/archopht.1996.01100140443012.

    PubMed 8859084

  • Klein R, Klein BE, Moss SE, Meuer SM. The epidemiology of retinal vein occlusion: the Beaver Dam Eye Study. Trans Am Ophthalmol Soc. 2000;98:133-41; discussion 141-3.

    PubMed 11190017

  • Brown DM, Campochiaro PA, Singh RP, Li Z, Gray S, Saroj N, Rundle AC, Rubio RG, Murahashi WY; CRUISE Investigators. Ranibizumab for macular edema following central retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology. 2010 Jun;117(6):1124-1133.e1. doi: 10.1016/j.ophtha.2010.02.022. Epub 2010 Apr 9.

    PubMed 20381871

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Minocycline and Bevacizumab in people with Retinal Vein Occlusion, run by National Eye Institute (NEI) at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 42 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 Eye at 12 Months Compared to Baseline. (time frame: Baseline to Month 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01468844, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2021.

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