Ignite Creation Date:
2024-05-05 @ 4:59 PM
Last Modification Date:
2024-10-26 @ 9:27 AM
Study NCT ID:
NCT00367133
Status:
COMPLETED
Last Update Posted:
2016-08-26
First Post:
2006-08-03
Brief Title:
Intravitreal Triamcinolone Acetonide Versus Laser for Diabetic Macular Edema
Sponsor:
Jaeb Center for Health Research
Organization:
Jaeb Center for Health Research
Study Overview
Official Title:
A Randomized Trial Comparing Intravitreal Triamcinolone Acetonide and Laser Photocoagulation for Diabetic Macular Edema
Status:
COMPLETED
Status Verified Date:
2016-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
IVT
Brief Summary:
The study involves the enrollment of patients over 18 years of age with diabetic macular edemaDME Patients with one study eye will be randomly assigned stratified by visual acuity and prior laser with equal probability to one of the three treatment groups
1 Laser photocoagulation
2 1mg intravitreal triamcinolone acetonide injection
3 4mg intravitreal triamcinolone acetonide injection
For patients with two study eyes both eyes eligible at the time of randomization the right eye stratified by visual acuity and prior laser will be randomly assigned with equal probabilities to one of the three treatment groups listed above The left eye will be assigned to the alternative treatment laser or triamcinolone If the left eye is assigned to triamcinolone then the dose 1mg or 4 mg will be randomly assigned to the left eye with equal probability stratified by visual acuity and prior laser
The study drug triamcinolone acetonide has been manufactured as a sterile intravitreal injectable by Allergan Study eyes assigned to an intravitreal triamcinolone injection will receive a dose of either 1mg or 4mg There is no indication of which treatment regimen will be better
Patients enrolled into the study will be followed for three years and will have study visits every 4 months after receiving their assigned study treatment In addition standard of care post-treatment visits will be performed at 4 weeks after each intravitreal injection
1 Laser photocoagulation
2 1mg intravitreal triamcinolone acetonide injection
3 4mg intravitreal triamcinolone acetonide injection
For patients with two study eyes both eyes eligible at the time of randomization the right eye stratified by visual acuity and prior laser will be randomly assigned with equal probabilities to one of the three treatment groups listed above The left eye will be assigned to the alternative treatment laser or triamcinolone If the left eye is assigned to triamcinolone then the dose 1mg or 4 mg will be randomly assigned to the left eye with equal probability stratified by visual acuity and prior laser
The study drug triamcinolone acetonide has been manufactured as a sterile intravitreal injectable by Allergan Study eyes assigned to an intravitreal triamcinolone injection will receive a dose of either 1mg or 4mg There is no indication of which treatment regimen will be better
Patients enrolled into the study will be followed for three years and will have study visits every 4 months after receiving their assigned study treatment In addition standard of care post-treatment visits will be performed at 4 weeks after each intravitreal injection
Detailed Description:
Diabetic retinopathy is a major cause of visual impairment in the United States Diabetic macular edema DME is a manifestation of diabetic retinopathy that produces loss of central vision Data from the Wisconsin Epidemiologic Study of Diabetic Retinopathy WESDR estimate that after 15 years of known diabetes the prevalence of diabetic macular edema is approximately 20 in patients with type 1 diabetes mellitus DM 25 in patients with type 2 DM who are taking insulin and 14 in patients with type 2 DM who do not take insulin
In a review of three early studies concerning the natural history of diabetic macular edema Ferris and Patz found that 53 of 135 eyes with diabetic macular edema presumably all involving the center of the macula lost two or more lines of visual acuity over a two year period In the Early Treatment Diabetic Retinopathy Study ETDRS 33 of 221 untreated eyes available for follow-up at the 3-year visit all with edema involving the center of the macula at baseline had experienced a 15 or more letter decrease in visual acuity score equivalent to a doubling of the visual angle eg 2025 to 2050 and termed moderate visual acuity loss
In the ETDRS focalgrid photocoagulation of eyes with clinically significant macular edema CSME reduced the risk of moderate visual loss by approximately 50 from 24 to 12 three years after initiation of treatment Therefore 12 of treated eyes developed moderate visual loss in spite of treatment Furthermore approximately 40 of treated eyes that had retinal thickening involving the center of the macula at baseline still had thickening involving the center at 12 months as did 25 of treated eyes at 36 months
Although several treatment modalities are currently under investigation the only demonstrated means to reduce the risk of vision loss from diabetic macular edema are laser photocoagulation as demonstrated by the ETDRS and intensive glycemic control as demonstrated by the Diabetes Control and Complications Trial DCCT and the United Kingdom Prospective Diabetes Study UKPDS In the DCCT intensive glucose control reduced the risk of onset of diabetic macular edema by 23 compared with conventional treatment Long-term follow-up of patients in the DCCT show a sustained effect of intensive glucose control with a 58 risk reduction in the development of diabetic macular edema for the DCCT patients followed in the Epidemiology of Diabetes Interventions and Complications Study
The frequency of an unsatisfactory outcome following laser photocoagulation in some eyes with diabetic macular edema has prompted interest in other treatment modalities One such treatment is pars plana vitrectomy These studies suggest that vitreomacular traction or the vitreous itself may play a role in increased retinal vascular permeability Removal of the vitreous or relief of mechanical traction with vitrectomy and membrane stripping may be followed by substantial resolution of macular edema and corresponding improvement in visual acuity However this treatment may be applicable only to a specific subset of eyes with diabetic macular edema It also requires a complex surgical intervention with its inherent risks recovery time and expense Other treatment modalities such as pharmacologic therapy with oral protein kinase C inhibitors and antibodies targeted at vascular endothelial growth factor VEGF are under investigation The use of intravitreal corticosteroids is another treatment modality that has generated recent interest
The optimal dose of corticosteroid to maximize efficacy with minimum side effects is not known A 4mg dose of Kenalog is principally being used in clinical practice However this dose has been used based on feasibility rather than scientific principles
There is also experience using Kenalog doses of 1mg and 2mg These doses anecdotally have been reported to reduce the macular edema There is a rationale for using a dose lower than 4mg Glucocorticoids bind to glucocorticoid receptors in the cell cytoplasm and the steroid-receptor complex moves to the nucleus where it regulates gene expression The steroid-receptor binding occurs with high affinity low dissociation constant Kd which is on the order of 5 to 9 nanomolar Complete saturation of all the receptors occurs about 20-fold higher levels ie about 100-200 nanomolar A 4mg dose of triamcinolone yields a final concentration of 75 millimolar or nearly 10000-fold more than the saturation dose Thus the effect of a 1mg dose may be equivalent to that of a 4mg dose because compared to the 10000-fold saturation a 4-fold difference in dose is inconsequential It is also possible that higher doses of corticosteroid could be less effective than lower doses due to down-regulation of the receptor The steroid implant studies provide additional justification for evaluating a lower dose a 05mg device which delivers only 05 micrograms per day has been observed to have a rapid effect in reducing macular edema
There has been limited experience using doses greater than 4mg Jonas case series reported results using a 25mg dose However others have not been able to replicate this dose using the preparation procedure described by Jonas
In the trial 4mg and 1mg doses will be evaluated The former will be used because it is the dose that is currently most commonly used in clinical practice and the latter because there is reasonable evidence for efficacy and the potential for lower risk Although there is good reason to believe that a 1mg dose will reduce the macular edema it is possible that the retreatment rate will be higher with this dose compared with 4mg since the latter will remain active in the eye for a longer duration than the former Insufficient data are available to warrant evaluating a dose higher than 4mg at this time
In a review of three early studies concerning the natural history of diabetic macular edema Ferris and Patz found that 53 of 135 eyes with diabetic macular edema presumably all involving the center of the macula lost two or more lines of visual acuity over a two year period In the Early Treatment Diabetic Retinopathy Study ETDRS 33 of 221 untreated eyes available for follow-up at the 3-year visit all with edema involving the center of the macula at baseline had experienced a 15 or more letter decrease in visual acuity score equivalent to a doubling of the visual angle eg 2025 to 2050 and termed moderate visual acuity loss
In the ETDRS focalgrid photocoagulation of eyes with clinically significant macular edema CSME reduced the risk of moderate visual loss by approximately 50 from 24 to 12 three years after initiation of treatment Therefore 12 of treated eyes developed moderate visual loss in spite of treatment Furthermore approximately 40 of treated eyes that had retinal thickening involving the center of the macula at baseline still had thickening involving the center at 12 months as did 25 of treated eyes at 36 months
Although several treatment modalities are currently under investigation the only demonstrated means to reduce the risk of vision loss from diabetic macular edema are laser photocoagulation as demonstrated by the ETDRS and intensive glycemic control as demonstrated by the Diabetes Control and Complications Trial DCCT and the United Kingdom Prospective Diabetes Study UKPDS In the DCCT intensive glucose control reduced the risk of onset of diabetic macular edema by 23 compared with conventional treatment Long-term follow-up of patients in the DCCT show a sustained effect of intensive glucose control with a 58 risk reduction in the development of diabetic macular edema for the DCCT patients followed in the Epidemiology of Diabetes Interventions and Complications Study
The frequency of an unsatisfactory outcome following laser photocoagulation in some eyes with diabetic macular edema has prompted interest in other treatment modalities One such treatment is pars plana vitrectomy These studies suggest that vitreomacular traction or the vitreous itself may play a role in increased retinal vascular permeability Removal of the vitreous or relief of mechanical traction with vitrectomy and membrane stripping may be followed by substantial resolution of macular edema and corresponding improvement in visual acuity However this treatment may be applicable only to a specific subset of eyes with diabetic macular edema It also requires a complex surgical intervention with its inherent risks recovery time and expense Other treatment modalities such as pharmacologic therapy with oral protein kinase C inhibitors and antibodies targeted at vascular endothelial growth factor VEGF are under investigation The use of intravitreal corticosteroids is another treatment modality that has generated recent interest
The optimal dose of corticosteroid to maximize efficacy with minimum side effects is not known A 4mg dose of Kenalog is principally being used in clinical practice However this dose has been used based on feasibility rather than scientific principles
There is also experience using Kenalog doses of 1mg and 2mg These doses anecdotally have been reported to reduce the macular edema There is a rationale for using a dose lower than 4mg Glucocorticoids bind to glucocorticoid receptors in the cell cytoplasm and the steroid-receptor complex moves to the nucleus where it regulates gene expression The steroid-receptor binding occurs with high affinity low dissociation constant Kd which is on the order of 5 to 9 nanomolar Complete saturation of all the receptors occurs about 20-fold higher levels ie about 100-200 nanomolar A 4mg dose of triamcinolone yields a final concentration of 75 millimolar or nearly 10000-fold more than the saturation dose Thus the effect of a 1mg dose may be equivalent to that of a 4mg dose because compared to the 10000-fold saturation a 4-fold difference in dose is inconsequential It is also possible that higher doses of corticosteroid could be less effective than lower doses due to down-regulation of the receptor The steroid implant studies provide additional justification for evaluating a lower dose a 05mg device which delivers only 05 micrograms per day has been observed to have a rapid effect in reducing macular edema
There has been limited experience using doses greater than 4mg Jonas case series reported results using a 25mg dose However others have not been able to replicate this dose using the preparation procedure described by Jonas
In the trial 4mg and 1mg doses will be evaluated The former will be used because it is the dose that is currently most commonly used in clinical practice and the latter because there is reasonable evidence for efficacy and the potential for lower risk Although there is good reason to believe that a 1mg dose will reduce the macular edema it is possible that the retreatment rate will be higher with this dose compared with 4mg since the latter will remain active in the eye for a longer duration than the former Insufficient data are available to warrant evaluating a dose higher than 4mg at this time
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| U10EY018817-03 | NIH | None | None |
| U10EY014229-07 | NIH | None | None |
| U10EY014231-09 | NIH | None | httpsreporternihgovquickSearchU10EY014231-09 |