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Utility of Intravitreal Methotrexate in Diabetic Macular Edema Resistant to Conventional Therapies

Primary Purpose

Diabetic Macular Edema

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Methotrexate intravenous 25mg/ml
Sponsored by
Wake Forest University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetic Macular Edema focused on measuring resistant diabetic macular edema

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Wake Forest Baptist Health Eye Center

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Methotrexate 25mg/ml

Arm Description

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.

Outcomes

Primary Outcome Measures

30% Decrease in One Subfield Thickness on Optical Coherence Tomography (OCT) 4 Weeks After the Last Intraocular Injection

Secondary Outcome Measures

Number of Participants With Increase in Visual Acuity (VA) Two Lines or More at the End of One Month After the Last Intraocular Injection
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.

Full Information

First Posted
October 22, 2008
Last Updated
December 26, 2017
Sponsor
Wake Forest University
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1. Study Identification

Unique Protocol Identification Number
NCT00779142
Brief Title
Utility of Intravitreal Methotrexate in Diabetic Macular Edema Resistant to Conventional Therapies
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2017
Overall Recruitment Status
Terminated
Why Stopped
recent research indicates Lucentis to be an effictive treatment
Study Start Date
September 2011 (undefined)
Primary Completion Date
August 2012 (Actual)
Study Completion Date
August 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Wake Forest University

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Macular Edema
Keywords
resistant diabetic macular edema

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Methotrexate 25mg/ml
Arm Type
Other
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Methotrexate intravenous 25mg/ml
Other Intervention Name(s)
Methotrexate
Intervention Description
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.
Primary Outcome Measure Information:
Title
30% Decrease in One Subfield Thickness on Optical Coherence Tomography (OCT) 4 Weeks After the Last Intraocular Injection
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
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
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shree K Kurup, MD
Organizational Affiliation
Wake Forest Baptist Health Eye Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Wake Forest Baptist Health Eye Center
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
17159036
Citation
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.
Results Reference
background
PubMed Identifier
18328456
Citation
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.
Results Reference
background
PubMed Identifier
18398360
Citation
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.
Results Reference
background
PubMed Identifier
18327132
Citation
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.
Results Reference
background
PubMed Identifier
17056381
Citation
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.
Results Reference
background
PubMed Identifier
17564935
Citation
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.
Results Reference
background

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Utility of Intravitreal Methotrexate in Diabetic Macular Edema Resistant to Conventional Therapies

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