Non-infectious Intermediate and Posterior Uveitis Clinical Trial
— MEXXOfficial title:
Treatment of Non-infectious Panuveitis, Intermediate and Posterior Uveitis Associated Macular Edema With Intravitreal Methotrexate
| Verified date | July 2018 |
| Source | National Institutes of Health Clinical Center (CC) |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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 times a day for 1 week following the injection, and a dose of
folic acid to be taken by mouth the day after the injection.
- Participants who tolerate the initial injection may continue to receive injections in
their study eye every month for 6 months. After 6 months, participants who show
improvement from the injections may be evaluated to receive additional injections every
4 to 8 weeks until researchers end the study.
| Status | Terminated |
| Enrollment | 2 |
| Est. completion date | January 2013 |
| Est. primary completion date | January 2013 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
INCLUSION CRITERIA: 1. Participant must be 18 years of age or older. 2. Participant must understand and sign the protocol's informed consent document. 3. Participant is willing to comply with the study procedures and return for all study visits. 4. Participant has chronic macular edema secondary to non-infectious panuveitis, posterior or intermediate uveitis in at least one eye (the study eye) that has: 1. not been responsive to conventional immunosuppressive therapy in the past 3 months; OR 2. recurred while on conventional immunosuppressive therapy. 5. Participant has central macular thickness of = 270 microns in the study eye. 6. Participant has visual acuity of 20/400 or better (= 19 ETDRS letters) in the study eye. 7. Female participants of childbearing potential must not be pregnant or breast-feeding, must have a negative serum pregnancy test at screening and must be willing to undergo serum pregnancy tests throughout the study. 8. Both female participants of childbearing potential (see Appendix 1 for definition) 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 six months after the last study medication injection. 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 (tubal ligation). EXCLUSION CRITERIA: 1. Participant is in another investigational study and actively receiving investigational therapy for macular edema. 2. Participant has evidence of infectious panuveitis, posterior or intermediate uveitis in either eye. 3. Participant is expected to need ocular surgery in the study eye during the course of the trial. 4. Participant had intraocular surgery in the study eye within the past 90 days. 5. Participant had an injection of bevacizumab or ranibizumab within the past four weeks in the study eye. 6. Participant had an injection of triamcinolone within the past six weeks in the study eye. 7. Participant has a systemic condition that, in the opinion of the investigator, would preclude participation in the study. 8. Participant has significant cataract or media opacity in the study eye that makes posterior segment visualization difficult as determined by investigator. 9. Participant has a confirmed positive serologic and/or molecular test for HIV-1/2. |
| Country | Name | City | State |
|---|---|---|---|
| United States | National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland |
| Lead Sponsor | Collaborator |
|---|---|
| National Eye Institute (NEI) |
United States,
Kiss CG, Barisani-Asenbauer T, Maca S, Richter-Mueksch S, Radner W. Reading performance of patients with uveitis-associated cystoid macular edema. Am J Ophthalmol. 2006 Oct;142(4):620-4. — View Citation
Lardenoye CW, van Kooij B, Rothova A. Impact of macular edema on visual acuity in uveitis. Ophthalmology. 2006 Aug;113(8):1446-9. — View Citation
Rothova A. Inflammatory cystoid macular edema. Curr Opin Ophthalmol. 2007 Nov;18(6):487-92. Review. — View Citation
van Kooij B, Rothova A, de Vries P. The pros and cons of intravitreal triamcinolone injections for uveitis and inflammatory cystoid macular edema. Ocul Immunol Inflamm. 2006 Apr;14(2):73-85. Review. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Number of Participants Who Meet the Definition of Treatment Success Within 12 Weeks From Baseline. | 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 |
12 weeks | |
| Secondary | Change in Optical Coherence Tomography (OCT) Excess Retinal Thickening in the Study Eye at 4 Weeks Compared to Baseline | 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. |
Baseline and Week 4 | |
| Secondary | Change in Optical Coherence Tomography (OCT) Excess Retinal Thickening in the Study Eye at 8 Weeks Compared to Baseline | 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. |
Baseline and Week 8 | |
| Secondary | Change in Optical Coherence Tomography (OCT) Excess Retinal Thickening in the Study Eye at 12 Weeks Compared to Baseline | 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. |
Baseline and Week 12 | |
| Secondary | Change in Optical Coherence Tomography (OCT) Excess Retinal Thickening in the Study Eye at 16 Weeks Compared to Baseline | 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. |
Baseline and Week 16 | |
| Secondary | Change in Optical Coherence Tomography (OCT) Excess Retinal Thickening in the Study Eye at 20 Weeks Compared to Baseline | 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. |
Baseline and Week 20 | |
| Secondary | Change in Optical Coherence Tomography (OCT) Excess Retinal Thickening in the Study Eye at 24 Weeks Compared to Baseline | 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. |
Baseline and Week 24 | |
| Secondary | Change in Optical Coherence Tomography (OCT) Central Macular Thickness in the Study Eye at 4 Weeks Compared to Baseline | Central-subfield macular thickness 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. |
Baseline and Week 4 | |
| Secondary | Change in Optical Coherence Tomography (OCT) Central Macular Thickness in the Study Eye at 8 Weeks Compared to Baseline | Central-subfield macular thickness 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. |
Baseline and Week 8 | |
| Secondary | Change in Optical Coherence Tomography (OCT) Central Macular Thickness in the Study Eye at 12 Weeks Compared to Baseline | Central-subfield macular thickness 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. |
Baseline and Week 12 | |
| Secondary | Change in Optical Coherence Tomography (OCT) Central Macular Thickness in the Study Eye at 16 Weeks Compared to Baseline | Central-subfield macular thickness 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. |
Baseline and Week 16 | |
| Secondary | Change in Optical Coherence Tomography (OCT) Central Macular Thickness in the Study Eye at 20 Weeks Compared to Baseline | Central-subfield macular thickness 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. |
Baseline and Week 20 | |
| Secondary | Change in Optical Coherence Tomography (OCT) Central Macular Thickness in the Study Eye at 24 Weeks Compared to Baseline | Central-subfield macular thickness 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. |
Baseline and Week 24 | |
| Secondary | Changes in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) in the Study Eye at 4 Weeks Compared to Baseline | Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. 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. |
Baseline and Week 4 | |
| Secondary | Changes in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) in the Study Eye at 8 Weeks Compared to Baseline | Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. 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. |
Baseline and Week 8 | |
| Secondary | Changes in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) in the Study Eye at 12 Weeks Compared to Baseline | Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. 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. |
Baseline and Week 12 | |
| Secondary | Changes in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) in the Study Eye at 16 Weeks Compared to Baseline | Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. 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. |
Baseline and Week 16 | |
| Secondary | Changes in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) in the Study Eye at 24 Weeks Compared to Baseline | Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. 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. |
Baseline and Week 24 | |
| Secondary | Changes in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) in the Study Eye at 20 Weeks Compared to Baseline | Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. 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. |
Baseline and Week 20 | |
| Secondary | Number of Participants Presenting No Change in the Area of Leakage in the Study Eye as Seen on Fluorescein Angiography (FA) Imaging at Week 12 as Compared to Baseline | Fluorescein angiography (FA) images were obtained via a standard digital imaging system (OIS, Sacramento, CA). Three retinal specialists independently graded the area of late fluorescein leakage (at approximately 10 minutes) in each eye using a region-of-interest tool in an image analysis software package (NIH ImageJ, Bethesda, MD). 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. |
Baseline and Week 12 | |
| Secondary | Number of Participants Presenting No Change in the Area of Leakage in the Study Eye as Seen on Fluorescein Angiography (FA) Imaging at Week 24 as Compared to Baseline | Fluorescein angiography (FA) images were obtained via a standard digital imaging system (OIS, Sacramento, CA). Three retinal specialists independently graded the area of late fluorescein leakage (at approximately 10 minutes) in each eye using a region-of-interest tool in an image analysis software package (NIH ImageJ, Bethesda, MD). 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. |
Baseline and Week 24 | |
| Secondary | Number of Participants Presenting the Same Autofluorescence Patterns in the Study Eye as Seen on Fundus Autofluorescence (FAF) Imaging at Week 12 as Observed at Baseline | Fundus autofluorescence patterns were assessed using fundus autofluorescence (FAF) imaging, a non-invasive technique that uses a confocal scanning ophthalmoscope to detect naturally-fluorescing lipofuscin. 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. |
Baseline and Week 12 | |
| Secondary | Number of Participants Presenting the Same Autofluorescence Patterns in the Study Eye as Seen on Fundus Autofluorescence (FAF) Imaging at Week 24 as Observed at Baseline | Fundus autofluorescence patterns were assessed using fundus autofluorescence (FAF) imaging, a non-invasive technique that uses a confocal scanning ophthalmoscope to detect naturally-fluorescing lipofuscin. 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. |
Baseline and Week 24 | |
| Secondary | Number of Participants Experiencing a Complete Resolution of Fluid as Seen on OCT at Any Time During the Study Period | Baseline and Week 74 | ||
| Secondary | Observation of Dose Reduction of Systemic Immunosuppression or Steroids Over the Course of the Study Period | This study terminated early due to lack of recruitment; therefore, we chose not to report due to insufficient data. | Baseline and Week 74 | |
| Secondary | Cytokine Analysis on Aqueous Samples to Assess Whether Intravitreal Injection of Methotrexate Affects Aqueous Inflammatory Cytokine Levels | This study terminated early due to lack of recruitment; therefore, we chose not to report due to insufficient data. | Baseline and Week 74 |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT00326508 -
Combination Daclizumab/Denileukin Diftitox to Treat Uveitis
|
Phase 2 |