Diabetic Macular EdemaNCT00779142
Utility of Intravitreal Methotrexate in Diabetic Macular Edema Resistant to Conventional Therapies
A study testing Methotrexate intravenous 25mg/ml in people with Diabetic Macular Edema, run by Wake Forest University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Diabetic Macular Edema
- What is being tested?
- Methotrexate intravenous 25mg/ml
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2011to Aug 2012
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 19Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Wake Forest Baptist Health Eye Center
Winston-Salem, North Carolina, 27157
About this study
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
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.
Read the 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.
- Conditions
- Diabetic Macular Edema
- Being tested
- Methotrexate intravenous 25mg/ml
- Keywords
- resistant diabetic macular edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methotrexate intravenous 25mg/mlDrug
Also called Methotrexate
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.
| Study group | Role | What they receive |
|---|---|---|
| Methotrexate 25mg/ml | Other | 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. Receives: Drug: Methotrexate intravenous 25mg/ml |
What is being measured
The primary outcome is the main question the study is designed to answer.
30% Decrease in One Subfield Thickness on Optical Coherence Tomography (OCT) 4 Weeks After the Last Intraocular Injection
Measured: 4 weeks
Secondary outcomes (2)
Number of Participants With Increase in Visual Acuity (VA) Two Lines or More at the End of One Month After the Last Intraocular Injection
Measured: 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.
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2008 (estimated)
- Study startSep 2011
- Primary completionAug 2012
- Study completionAug 2012
Why it stopped: recent research indicates Lucentis to be an effictive treatment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Diabetic Macular EdemaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Shree K Kurup, MD, Principal investigator, Wake Forest Baptist Health Eye Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00779142
- Sponsor's protocol ID
- 5865 Methotrexate
- Status last verified
- Nov 2017
- First submitted
- 22 Oct 2008
- Last updated
- 23 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
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.
PubMed 17159036Shimura 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.
PubMed 18328456Vasconcelos-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.
PubMed 18398360Hartley 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.
PubMed 18327132Hardwig 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.
PubMed 17056381Ghajarnia 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.
PubMed 17564935
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00779142
- Acronym / sponsor ID
- 5865 Methotrexate
- Conditions
- Diabetic Macular Edema
- Keywords
- resistant diabetic macular edema
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: recent research indicates Lucentis to be an effictive treatment
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Wake Forest UniversityUniversity, hospital or other
- Study start
- Sep 2011
- Primary completion
- Aug 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 24 Oct 2008 (estimated)
- Results
- Posted 30 Jun 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Methotrexate 25mg/ml | Other | Drug: Methotrexate intravenous 25mg/mlMethotrexate 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. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Methotrexate intravenous 25mg/mlAlso: MethotrexateMethotrexate 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. | Drug | Methotrexate 25mg/ml |
Primary outcome
30% Decrease in One Subfield Thickness on Optical Coherence Tomography (OCT) 4 Weeks After the Last Intraocular Injection
Time frame: 4 weeks
2 secondary outcomes
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17159036Rein 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.
- Background: PubMed 18328456Shimura 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.
- Background: PubMed 18398360Vasconcelos-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.
- Background: PubMed 18327132Hartley 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.
- Background: PubMed 17056381Hardwig 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.
- Background: PubMed 17564935Ghajarnia 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shree K Kurup, MD principal investigator
Wake Forest Baptist Health Eye Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Methotrexate intravenous 25mg/ml in people with Diabetic Macular Edema, run by Wake Forest University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 23 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jun 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
30% Decrease in One Subfield Thickness on Optical Coherence Tomography (OCT) 4 Weeks After the Last Intraocular Injection (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00779142, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2018.