Utility of Intravitreal Methotrexate in Diabetic Macular Edema Resistant to Conventional Therapies
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Purpose
It is well known that blindness is one of the most feared disabilities expressed by patients in the United States. Estimates of the economic impact of visual disability in the current population exceed 30 million US dollars in this country alone. The reasons for this figure are many; however age related macular degeneration (ARMD), diabetic retinopathy, glaucoma and uveitis are responsible for the majority of permanent visual disability and hence the costs in both quality of life and placing an economic burden on society. Research that may help reverse various abnormal biological responses that lead to or worsen clinical manifestations of diabetic retinopathy would be valuable.
| Condition | Intervention |
|---|---|
|
Diabetic Macular Edema |
Drug: Methotrexate intravenous 25mg/ml |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Evaluation of the Utility of Intravitreal Methotrexate in Patients With Recalcitrant Diabetic Macular Edema in an Open Label, Nonrandomized, Uncontrolled, Interventional Pilot Trial |
- Primary Would be 30% Decrease in One Subfield Thickness on Optical Coherence Tomography (OCT) 4 Weeks After the Last Intraocular Injection [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
- Secondary Would be Increase in Visual Acutiy (VA) Two Lines or More at the End of One Month After the Last Intraocular Injection. [ Time Frame: 1 month ] [ Designated as safety issue: No ]
- Secondary Would be Significant Clinical Improvement (Judged at the Slit Lamp Exam Using a 90D Lens) in Macular Edema at the End of One Month After the Last Intraocular Injection. [ Time Frame: 1 month ] [ Designated as safety issue: No ]
| Enrollment: | 2 |
| Study Start Date: | September 2011 |
| Study Completion Date: | August 2012 |
| Primary Completion Date: | August 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Methotrexate 25mg/ml
Methotrexate intravenous 25mg/ml: Methotrexate intravenous 25mg/ml delivered once or twice (based on the therapeutic response) over a period of 2 months maximum. Total dosage 400ug in each dose to subjects with diabetic macular edema resistant to conventional therapies.
|
Drug: Methotrexate intravenous 25mg/ml
Methotrexate intravenous 25mg/ml delivered once or twice (based on the therapeutic response) over a period of 2 months maximum. Total dosage 400ug in each dose. Statistical analysis would not be applicable in this small sample.
Other Name: Methotrexate
|
Detailed Description:
The most common reason for decreased vision in diabetic retinopathy is macular edema. Current approaches to macular edema include FDA approved interventions such as laser and better underlying control of the disease and co morbid conditions. 'Off label' interventions include intravitreal triamcinolone and bevacizumab, both of which have been demonstrated to be efficacious; at least in the short term (weeks) but carry significant risks. Surgical approaches are still controversial and have not shown long term benefits. Unfortunately, there are subsets of patients resistant to any of the above therapies. Intravitreal therapies utilizing methotrexate 400 ug (MTX) have been used for other ophthalmologic conditions associated with inflammation driven macular edema. bevacizumab an anti VEGF agent has been utilized in diseases other than macular degeneration with a favorable effect. It is known that certain similar inflammatory mediators play a role in diabetic macular edema. It would be logical to evaluate the efficacy of MTX an anti inflammatory anti metabolite at low concentrations in diabetic patients with macular edema who have failed conventional FDA approved and well studied off label therapies that involve laser and/or intravitreal drugs.
Eligibility| Ages Eligible for Study: | 18 Years to 85 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Adult patients (18 years and older) with clinically significant macular edema (CSME) with visual acuity less than 20/60 to Hand motion in the study eye.
- Patients should have persistent CSME three months after laser therapy or three months after intraocular injection of Avastin or triamcinolone. These interventions could be multiple or combined.
- Optical coherence tomography (OCT) scan demonstrating more than 275 microns retinal thickness in central subfield of study eye.
- Ability to understand study instructions, interventions and potential complications.
- History of reasonably controlled Diabetes mellitus (DM), ≤ 8.5HbA1c that has been evaluated in the last 3 months.
- Ability to undergo contraceptive protection during and 3 months after intraocular injections.
- Clear demonstration (in female patients) of commitment to avoid pregnancy and a negative urine pregnancy test at baseline for women of childbearing potential.
- Clear understanding of teratogenic potential of MTX.
Exclusion Criteria:
- History of allergy to MTX.
- An ocular condition is present such that, in the opinion of the investigator, visual acuity loss would not improve from resolution of macular edema (e.g., foveal atrophy, pigment abnormalities, dense subfoveal hard exudates, nonretinal condition.
- An ocular condition is present (other than diabetes) 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, epiretinal membrane, etc.).
- An eye treated for Glaucoma
- Eyes that underwent vitrectomy
- History of intraocular malignancies.
- Intraocular surgery with the prior 3 months.
- Recent significant change in diabetic medications.
- Insulin usage less than a year.
- Life threatening co morbidities such as cancer under therapy.
- Use of oral, intravenous, periocular or intraocular corticosteroids (steroids) in prior 3 months.
- Liver function that exceeds three times the upper limit of normal at baseline, or within 6 weeks of that appointment.
- Pregnant females.
- Vitreous hemorrhage (active) in study eye
- Anticipation of the need for laser pan retinal photocoagulation in the next 6 months.
- Media opacities
- Herpetic disease of cornea
- Corneal dystrophy with significant corneal edema.
- Any major surgery within the last 30 days
Contacts and LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT00779142
| United States, North Carolina | |
| Wake Forest Baptist Health Eye Center | |
| Winston Salem, North Carolina, United States, 27157 | |
| Principal Investigator: | Shree K Kurup, MD | Wake Forest Baptist Health Eye Center |
More Information
Publications:
| Responsible Party: | Shree Kurup, Assistant Professor, Wake Forest School of Medicine |
| ClinicalTrials.gov Identifier: | NCT00779142 History of Changes |
| Other Study ID Numbers: | 5865 Methotrexate |
| Study First Received: | October 22, 2008 |
| Results First Received: | May 27, 2014 |
| Last Updated: | June 27, 2014 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Wake Forest School of Medicine:
|
resistant diabetic macular edema |
Additional relevant MeSH terms:
|
Edema Macular Edema Eye Diseases Macular Degeneration Retinal Degeneration Retinal Diseases Signs and Symptoms Methotrexate Abortifacient Agents Abortifacient Agents, Nonsteroidal Antimetabolites Antimetabolites, Antineoplastic Antineoplastic Agents |
Antirheumatic Agents Dermatologic Agents Enzyme Inhibitors Folic Acid Antagonists Immunologic Factors Immunosuppressive Agents Molecular Mechanisms of Pharmacological Action Nucleic Acid Synthesis Inhibitors Pharmacologic Actions Physiological Effects of Drugs Reproductive Control Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on February 25, 2015