- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00779142
Utility of Intravitreal Methotrexate in Diabetic Macular Edema Resistant to Conventional Therapies
December 26, 2017 updated by: Wake Forest University
Evaluation of the Utility of Intravitreal Methotrexate in Patients With Recalcitrant Diabetic Macular Edema in an Open Label, Nonrandomized, Uncontrolled, Interventional Pilot Trial
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.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
2
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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North Carolina
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Winston-Salem, North Carolina, United States, 27157
- Wake Forest Baptist Health Eye Center
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 85 years (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
OTHER: 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.
|
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 Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
30% Decrease in One Subfield Thickness on Optical Coherence Tomography (OCT) 4 Weeks After the Last Intraocular Injection
Time Frame: 4 weeks
|
4 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Number of Participants With Increase in Visual Acuity (VA) Two Lines or More at the End of One Month After the Last Intraocular Injection
Time Frame: 1 month
|
1 month
|
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
|
1 month
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Shree K Kurup, MD, Wake Forest Baptist Health Eye Center
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Rein DB, Zhang P, Wirth KE, Lee PP, Hoerger TJ, McCall N, Klein R, Tielsch JM, Vijan S, Saaddine J. The economic burden of major adult visual disorders in the United States. Arch Ophthalmol. 2006 Dec;124(12):1754-60. doi: 10.1001/archopht.124.12.1754. Erratum In: Arch Ophthalmol. 2007 Sep;125(9):1304.
- Shimura M, Nakazawa T, Yasuda K, Shiono T, Iida T, Sakamoto T, Nishida K. Comparative therapy evaluation of intravitreal bevacizumab and triamcinolone acetonide on persistent diffuse diabetic macular edema. Am J Ophthalmol. 2008 May;145(5):854-61. doi: 10.1016/j.ajo.2007.12.031. Epub 2008 Mar 6.
- Vasconcelos-Santos DV, Nehemy PG, Schachat AP, Nehemy MB. Secondary ocular hypertension after intravitreal injection of 4 mg of triamcinolone acetonide: incidence and risk factors. Retina. 2008 Apr;28(4):573-80. doi: 10.1097/IAE.0b013e31816079e8.
- Hartley KL, Smiddy WE, Flynn HW Jr, Murray TG. Pars plana vitrectomy with internal limiting membrane peeling for diabetic macular edema. Retina. 2008 Mar;28(3):410-9. doi: 10.1097/IAE.0b013e31816102f2.
- Hardwig PW, Pulido JS, Erie JC, Baratz KH, Buettner H. Intraocular methotrexate in ocular diseases other than primary central nervous system lymphoma. Am J Ophthalmol. 2006 Nov;142(5):883-5. doi: 10.1016/j.ajo.2006.06.002.
- Ghajarnia M, Kurup S, Eller A. The therapeutic effects of intravitreal bevacizumab in a patient with recalcitrant idiopathic polypoidal choroidal vasculopathy. Semin Ophthalmol. 2007 Apr-Jun;22(2):127-31. doi: 10.1080/08820530701421635.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
September 1, 2011
Primary Completion (ACTUAL)
August 1, 2012
Study Completion (ACTUAL)
August 1, 2012
Study Registration Dates
First Submitted
October 22, 2008
First Submitted That Met QC Criteria
October 22, 2008
First Posted (ESTIMATE)
October 24, 2008
Study Record Updates
Last Update Posted (ACTUAL)
January 23, 2018
Last Update Submitted That Met QC Criteria
December 26, 2017
Last Verified
November 1, 2017
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Eye Diseases
- Retinal Degeneration
- Retinal Diseases
- Macular Degeneration
- Macular Edema
- Edema
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Dermatologic Agents
- Reproductive Control Agents
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Methotrexate
Other Study ID Numbers
- 5865 Methotrexate
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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