Minocycline to Treat Branch Retinal Vein Occlusion

NCT01468831 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 11026311-EI-0263
• Study Type: interventional
• Target: 9
• Locations: 2 countries
• Sites: 2

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.

Conditions

Retinal Vein Occlusion

Keywords

Minocycline; Macular Edema

Outcome Measures

Primary Outcomes (1)

• 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 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.

  Baseline to Month 12

Secondary Outcomes (16)

• Number of Bevacizumab Injections From Baseline to 12 Months

  Baseline to Month 12

• Number of Bevacizumab Injections From Baseline to 24 Months

  Baseline to Month 24

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

  Baseline to Month 3

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

  Baseline to Month 6

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

  Baseline to Month 12

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Participants injected with bevacizumab for three months followed by PRN dosing and placebo twice daily for 24 months

Other: Placebo; Drug: Bevacizumab

Minocycline

EXPERIMENTAL

Participants injected with bevacizumab for three months followed by PRN dosing and 100mg minocycline twice daily for 24 months

Drug: Minocycline; Drug: Bevacizumab

Interventions

Minocycline DRUG

100 mg of minocycline in a pink opaque capsule

Minocycline

Placebo OTHER

Pill with inactive ingredients in a pink opaque capsule

Placebo

Bevacizumab DRUG

1.25 mg bevacizumab injection

Minocycline; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Female participants of childbearing potential and male participants able to father children must meet the following site-specific criteria:
• 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).
• Note: 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).

You may not qualify if:

• 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).
• a. 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:

Sponsors & Collaborators

• National Eye Institute (NEI): lead

Study Sites (2)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Bristol Eye Hospital

Bristol, United Kingdom

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Retinal Vein Occlusion; cyclopia sequence; Macular Edema

Interventions

Minocycline; Bevacizumab

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Venous Thrombosis; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Macular Degeneration; Retinal Degeneration

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Catherine Cukras, MD, PhD, Principal Investigator, NEI
• Organization: National Institutes of Health

cukrasc@nei.nih.gov

301-435-5061

Study Officials

• Catherine A Cukras, M.D.

  National Eye Institute (NEI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2011
• First Posted: November 10, 2011
• Study Start: March 28, 2012
• Primary Completion: February 25, 2020
• Study Completion: March 18, 2021
• Last Updated: January 26, 2022
• Results First Posted: January 26, 2022

Record last verified: 2021-10

Locations

GB (1); US (1)