Clinical Trial: Treatment of Non-infectious Intermediate and Posterior Uveitis Associated Macular Edema With Intravitreal Methotrexate

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Treatment of Non-infectious Panuveitis, Intermediate and Posterior Uveitis Associated Macular Edema With Intravitreal Methotrexate

Brief Summary:

BACKGROUND:

Uveitis comprises of a group of diseases associated with inflammation of the eye that can lead to vision loss. Some people with uveitis also have macular edema (swelling of the retina at the back of the eye). Uveitis and macular edema are treated with medications and sometimes surgery, but treatment does not always prevent vision loss. Previous research has shown that injections of methotrexate into the eye of people with eye disease other than uveitis can help relieve the inflammation, or swelling, that causes macular edema and can slow visual loss. However, it has not yet been approved as a treatment for macular edema associated with uveitis.

OBJECTIVES:

To evaluate the safety and effectiveness of methotrexate injections as a treatment for macular edema associated with uveitis.

ELIGIBILITY:

Individuals at least 18 years of age who have been diagnosed with uveitis and macular edema in at least one eye.

DESIGN:

  • This study requires at least nine visits to the National Eye Institute study clinic over a period of 6 months (24 weeks).
  • Participants will be screened with a physical and ophthalmic examination, medical history, blood and urine tests, and additional eye and other tests as needed.
  • Participants will receive a methotrexate injection in a selected treatment eye. After the injection, participants will receive antibiotic eye drops to place in the eye three times a day for the 3 days following the injection, leucovorin (folic acid) drops to place in the eye four ti

    Detailed Summary:

    OBJECTIVE:

    The study objective is to investigate the safety, tolerability and potential efficacy of intravitreal injections of methotrexate as a possible treatment for chronic macular edema secondary to panuveitis, posterior or intermediate uveitis.

    STUDY POPULATION:

    Five participants with chronic macular edema associated with panuveitis, posterior or intermediate uveitis will be initially enrolled. However, up to an additional two participants may be enrolled to account for participants who withdraw from the study prior to reaching Week 12. Eligibility criteria include macular edema in the study eye, which has not been responsive to conventional immunosuppressive therapy in the past three months, or the participant experienced a recurrence of macular edema while on conventional immunosuppressive therapy.

    STUDY DESIGN:

    In this single-center, prospective, uncontrolled, unmasked, Phase I/II clinical trial, intravitreal injections of methotrexate at a dose of 400 μg per 100 μL will be administered. There will be an induction phase and a pro re nata (PRN) phase. During the induction phase, participants will receive injections at baseline and Weeks 4, 8, 12, 16 and 20 in their study eye unless contraindicated. Additional safety visits will occur at Weeks 1 and 2. Beginning at Week 24, participants who agree to remain in the study will undergo evaluation for injection in the study eye PRN every 4-8 weeks. These participants will be followed for 4-8 weeks after the last enrolled participant completes his/her Week 24 visit.

    OUTCOME MEASURES:

    The primary outcome is the number
    Sponsor: National Eye Institute (NEI)

    Current Primary Outcome: Number of Participants Who Meet the Definition of Treatment Success Within 12 Weeks From Baseline. [ Time Frame: 12 weeks ]

    Treatment success is defined as achieving at least a 1-step decrease in the LogScore scale for central macular thickness.

    A decrease of at least 1-step on the logOCT scale, where Change in logOCT=log(follow-up thickness/200) - log(baseline thickness/200) is considered clinically significant. A 1-step decrease is equivalent to at least a 20% improvement of central macular thickness and represents greater than twice the variability of retinal thickness measurements (approximately 25-30 µ).

    Examples of OCT measurements with their corresponding LogScore, where LogScore=10xlogOCT are as follows:

    LogScore 0 = OCT 200 µm, LogScore 1 = OCT 250 µm, LogScore 2 = OCT 320 µm, LogScore 3 = OCT 400 µm, LogScore 4 = OCT 500 µm, LogScore 5 = OCT 640 µm, LogScore 6 = OCT 800 µm, LogScore 7 = OCT 1000 µm



    Original Primary Outcome: Number of participants who meet the definition of treatment success within 12 weeks from baseline. Treatment success is defined as a 25% decrease in excess retinal thickening in the study eye assessed by OCT as compared with baseline. [ Time Frame: 12 weeks ]

    Current Secondary Outcome:

    • Change in Optical Coherence Tomography (OCT) Excess Retinal Thickening in the Study Eye at 4 Weeks Compared to Baseline [ Time Frame: Baseline and Week 4 ]

      Excess retinal thickening was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.

      The participant's eye that met the study eye eligibility criteria was selected as the study eye. For cases in which both eyes met the study eye eligibility criteria, the study eye was selected according to the "choice of study eye in cases of bilateral disease" selection criteria outlined in the eligibility criteria.

    • Change in Optical Coherence Tomography (OCT) Excess Retinal Thickening in the Study Eye at 8 Weeks Compared to Baseline [ Time Frame: Baseline and Week 8 ]

      Excess retinal thickening was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.

      The participant's eye that met the study eye eligibility criteria was selected as the study eye. For cases in which both eyes met the study eye eligibility criteria, the study eye was selected according to the "choice of study eye in cases of bilateral disease" selection criteria outlined in the eligibility criteria.

    • Change in Optical Coherence Tomography (OCT) Excess Retinal Thickening in the Study Eye at 12 Weeks Compared to Baseline [ Time Frame: Baseline and Week 12 ]

      Excess retinal thickening was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.

      The participant's eye that met the study eye eligibility criteria was selected as the study eye. For cases in which both eyes met the study eye eligibility criteria, the study eye was selected according to the "choice of study eye in cases of bilateral disease" selection criteria outlined in the eligibility criteria.

    • Change in Optical Coherence Tomography (OCT) Excess Retinal Thickening in the Study Eye at 16 Weeks Compared to Baseline [ Time Frame: Baseline and Week 16 ]

      Excess retinal thickening was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.

      The participant's eye that met the study eye eligibility criteria was selected as the study eye. For cases in which both eyes met the study eye eligibility criteria, the study eye was selected according to the "choice of study eye in cases of bilateral disease" selection criteria outlined in the eligibility criteria.

    • Change in Optical Coherence Tomography (OCT) Excess Retinal Thickening in the Study Eye at 20 Weeks Compared to Baseline [ Time Frame: Baseline and Week 20 ]

      Excess retinal thickening was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.

      The participant's eye that met the study eye eligibility criteria was selected as the study eye. For cases in which both eyes met the study eye eligibility criteria, the study eye was selected according to the "choice of study eye in cases of bilateral disease" selection criteria outlined in the eligibility criteria.

    • Change in Optical Coherence Tomography (OCT) Excess Retinal Thickening in the Study Eye at 24 Weeks Compared to Baseline [ Time Frame: Baseline and Week 24 ]

      Excess retinal thickening was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.

      The participant's eye that met the study eye eligibility criteria was selected as the study eye. For cases in which both eyes met the study eye eligibility criteria, the study eye was selected according to the "choice of study eye in cases of bilateral disease" selection criteria outlined in the eligibility criteria.

    • Change in Optical Coherence Tomography (OCT) Central Macular Thickne

      Original Secondary Outcome:

      • Changes in excess retinal thickening, macular thickness, bcva, leakage on fa, autofluorescence patterns over study period. [ Time Frame: 12 and 24 weeks ]
      • Observation of dose reductions of systemic immunosuppression or steroids over the study period. [ Time Frame: 12 and 24 weeks ]


      Information By: National Institutes of Health Clinical Center (CC)

      Dates:
      Date Received: March 11, 2011
      Date Started: February 2011
      Date Completion:
      Last Updated: October 17, 2013
      Last Verified: October 2013