Diabetic Macular EdemaPhase 2RaScaLNCT00815360
Ranibizumab and Peripheral Scatter Laser in Patients With Diabetic Macular Edema and Peripheral Nonperfusion
A Phase 2 study testing intravitreal injection of ranibizumab, peripheral laser and intravitreal injection of triamcinolone acetonide in people with Diabetic Macular Edema, run by Retina Associates of Florida, P.A. at 1 site in United States.
Trial summary
To investigate the role of ranibizumab and angiographically-directed peripheral scatter laser therapy in patients with clinically-significant diabetic macular edema (CSME) and peripheral nonperfusion. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Macular Edema
- What is being tested?
- intravitreal injection of ranibizumab, peripheral laser and intravitreal injection of triamcinolone acetonide
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2008to Aug 2011
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects will be eligible if the following criteria are met:
- Ability to provide written informed consent and comply with study assessments for the full duration of the study
- Age > 18 years
- Patient related considerations:
- Patients with Type I or Type II diabetes
- Disease related considerations:
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- Study eye with clinically significant diabetic macular edema characterized by macular edema, peripheral nonperfusion, and absence of macular traction on clinical exam, UWFA, and OCT.
- Study eye with best corrected visual acuity between 20/40 (≤ 73 letters on Early Treatment of Diabetic Retinopathy Study (ETDRS) chart and 20/320 (≥ 19 letters on ETDRS chart) Other considerations
- Patient able to complete all study visits
- Female patients must be using two forms of contraception
Who cannot join
- Pregnancy (positive pregnancy test) or lactation. Premenopausal women not using adequate contraception. The following are considered effective means of contraception: surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an Intra Uterine Device, or contraceptive hormone implant or patch.
- Prior enrollment in the study
- Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated
- Participation in another simultaneous medical investigation or trial
- Therapy with intravitreal triamcinolone, pegaptanib, ranibizumab, or bevacizumab within the previous 3 months
- Previous panretinal scatter laser photocoagulation
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- Previous pars plana vitrectomy
- Visually-significant significant cataracts as primary reason for vision loss
- Uncontrolled or advanced glaucoma
- Patients on more than one anti-glaucoma agent
- Myocardial infarction or cerebrovascular accident within 6 months
- Subjects with poor glycemic control that have initiated intensive insulin treatment or plan to do so in the next 4 months
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Ranibizumab (rhuFab V2) and Scatter Laser Photocoagulation in Treatment of Patients With Clinically-significant Diabetic Macular Edema With Peripheral Retinal Nonperfusion (RaScaL)
To investigate the role of ranibizumab and angiographically-directed peripheral scatter laser therapy in patients with clinically-significant diabetic macular edema (CSME) and peripheral nonperfusion. We propose a novel treatment of CSME in a subgroup of patients defined by a combination of ultrawide-field angiography (UWFA) and optical coherence tomography (OCT). Within this classification scheme, patients with CSME are subdivided by the presence of: 1) focal macular leakage, 2) vitreomacular interface traction, and/or 3) peripheral nonperfusion. The successful treatment of diabetic macular edema would be dictated by pathophysiology-directed therapy based on this classification.
The subgroup of interest for this clinical trial is characterized by diabetic macular edema, peripheral nonperfusion on UWFA, and the absence of macular traction on OCT. This group of patients has previously not been well recognized or characterized due to limitations in previous, standard angiographic evaluation of the retinal periphery.
We postulate that this subcategory represents one with a high rate of failure of accepted therapies given persistence of the basic pathophysiologic mechanism for CSME, namely ischemia-induced production of Vascular Endothelial Growth Factor (VEGF) from the retinal periphery. This also represents a population of patients with likely recurrence of CSME despite treatment with anti-VEGF therapy alone for the same reason.
Read the detailed description
Diabetic retinopathy is a leading cause of moderate and severe visual loss in developed countries. It is of paramount socioeconomic impact as the prevalence of diabetes is sharply increasing, diabetic macular edema is the leading cause of vision loss in working age patients, it is a significant cause of vision loss in patients older than 65 years of age, it frequently affects patients bilaterally, and the costs of therapy are increasing.
Diabetic macular edema (DME) is the most common cause of vision loss in diabetic retinopathy. The pathophysiology of DME is complex and multifactorial. Chronic hyperglycemia, protein kinase C (PKC) formation, free radical accumulation, advanced glycation end-product (AGE) proteins, and ischemia-driven release of vascular endothelial growth factor (VEGF) are some of the better understood factors that contribute to chronic retinal arterial and capillary damage and increased permeability.
The RIDE and RISE Studies demonstrated the superiority of anti-VEGF monotherapy with ranibizumab over sham therapy, when all groups were allowed to receive macular laser therapy after month 3 based on predefined criteria. Furthermore, other studies have demonstrated VEGF inhibitors to be beneficial for DME, either as monotherapy or in combination with macular laser.
The benefit of VEGF antagonists in treating DME validates that the VEGF pathway is a key target. The need for repeated anti-VEGF injections to maintain the benefit of treatment begs the question whether persistent peripheral retinal ischemia may be driving VEGF production in at least a subset of patients with DME. Fluorescein angiographic studies of the mid- and far-periphery of diabetic patients by Shimizu in the 1980's demonstrated areas of peripheral retinal nonperfusion in diabetic patients. These findings have been reproduced and substantiated more recently utilizing a novel, commercially-available imaging system for ultrawide-field angiography (UWFA) that employs a scanning laser ophthalmoscope and an ellipsoidal mirror.
We investigated whether patients with diabetic macular edema associated with peripheral nonperfusion on UWFA would have improved visual acuity, resolution of retinal thickening on OCT, and durability of therapy using a novel strategy of a single intravitreal injection of Ranibizumab, a VEGF-A inhibitor + UWFA-guided peripheral Scatter Laser, or RaScaL. A second goal of the study was to guide DME treatment by the imaging signature of UWFA and OCT.
- Conditions
- Diabetic Macular Edema
- Being tested
- intravitreal injection of ranibizumab, peripheral laser, intravitreal injection of triamcinolone acetonide, macular laser
- Keywords
- diabetic macular edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
intravitreal injection of ranibizumabDrug
Also called treatment arm
intravitreal injection of 0.5 mg ranibizumab
peripheral laserProcedure or surgery
Also called treatment arm
ultra-widefield fluorescein angiography guided peripheral laser
intravitreal injection of triamcinolone acetonideDrug
Also called control arm
intravitreal injection of 4.0 mg triamcinolone acetonide
macular laserProcedure or surgery
Also called control arm
macular laser to areas of retinal thickening or leakage
| Study group | Role | What they receive |
|---|---|---|
| Treatment group | Experimental | 1. single intravitreal injection of ranibizumab (0.5 mg in 0.1 cc)
2. peripheral laser to areas of retinal nonperfusion on ultra-widefield fluorescein angiography Receives: Drug: intravitreal injection of ranibizumab; Procedure: peripheral laser |
| Control Group | Active comparator | 1. single intravitreal injection of triamcinolone acetonide (4.0 mg in 0.1 cc)
2. macular laser per treatment criteria Receives: Drug: intravitreal injection of triamcinolone acetonide; Procedure: macular laser |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Change in Best Corrected Visual Acuity (BCVA), as Assessed by the Number of Letters Read Correctly on the ETDRS Eye Chart at a Starting Test Distance of 4 Meters From Baseline to Month 6.
Measured: 6 months
Secondary outcomes (1)
Mean Central Foveal Thickness (CFT) on Optical Coherence Tomography (OCT) in Microns at 6 Months
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2008 (estimated)
- Study startFeb 2008
- Primary completionJul 2011
- Study completionAug 2011
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.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Retina Associates of Florida, P.A.
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ivan J. Suner, MD, Retina Associates of Florida, P.A.
- Investigators
- Ivan J Suner, MD, Principal investigator, Retina Associates of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00815360
- Sponsor's protocol ID
- Pro00002813
- Acronym
- RaScaL
- Status last verified
- Oct 2014
- First submitted
- 26 Dec 2008
- Last updated
- 5 Mar 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ranibizumab (rhuFab V2) and Scatter Laser Photocoagulation in Treatment of Patients With Clinically-significant Diabetic Macular Edema With Peripheral Retinal Nonperfusion (RaScaL)
- ClinicalTrials.gov ID
- NCT00815360
- Acronym / sponsor ID
- RaScaL / Pro00002813
- Conditions
- Diabetic Macular Edema
- Keywords
- diabetic macular edema
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Retina Associates of Florida, P.A.University, hospital or other
- Study start
- Feb 2008
- Primary completion
- Jul 2011 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 30 Dec 2008 (estimated)
- Results
- Posted 5 Mar 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To investigate the role of ranibizumab and angiographically-directed peripheral scatter laser therapy in patients with clinically-significant diabetic macular edema (CSME) and peripheral nonperfusion. We propose a novel treatment of CSME in a subgroup of patients defined by a combination of ultrawide-field angiography (UWFA) and optical coherence tomography (OCT). Within this classification scheme, patients with CSME are subdivided by the presence of: 1) focal macular leakage, 2) vitreomacular interface traction, and/or 3) peripheral nonperfusion. The successful treatment of diabetic macular edema would be dictated by pathophysiology-directed therapy based on this classification.
The subgroup of interest for this clinical trial is characterized by diabetic macular edema, peripheral nonperfusion on UWFA, and the absence of macular traction on OCT. This group of patients has previously not been well recognized or characterized due to limitations in previous, standard angiographic evaluation of the retinal periphery.
We postulate that this subcategory represents one with a high rate of failure of accepted therapies given persistence of the basic pathophysiologic mechanism for CSME, namely ischemia-induced production of Vascular Endothelial Growth Factor (VEGF) from the retinal periphery. This also represents a population of patients with likely recurrence of CSME despite treatment with anti-VEGF therapy alone for the same reason.
Detailed description
Diabetic retinopathy is a leading cause of moderate and severe visual loss in developed countries. It is of paramount socioeconomic impact as the prevalence of diabetes is sharply increasing, diabetic macular edema is the leading cause of vision loss in working age patients, it is a significant cause of vision loss in patients older than 65 years of age, it frequently affects patients bilaterally, and the costs of therapy are increasing.
Diabetic macular edema (DME) is the most common cause of vision loss in diabetic retinopathy. The pathophysiology of DME is complex and multifactorial. Chronic hyperglycemia, protein kinase C (PKC) formation, free radical accumulation, advanced glycation end-product (AGE) proteins, and ischemia-driven release of vascular endothelial growth factor (VEGF) are some of the better understood factors that contribute to chronic retinal arterial and capillary damage and increased permeability.
The RIDE and RISE Studies demonstrated the superiority of anti-VEGF monotherapy with ranibizumab over sham therapy, when all groups were allowed to receive macular laser therapy after month 3 based on predefined criteria. Furthermore, other studies have demonstrated VEGF inhibitors to be beneficial for DME, either as monotherapy or in combination with macular laser.
The benefit of VEGF antagonists in treating DME validates that the VEGF pathway is a key target. The need for repeated anti-VEGF injections to maintain the benefit of treatment begs the question whether persistent peripheral retinal ischemia may be driving VEGF production in at least a subset of patients with DME. Fluorescein angiographic studies of the mid- and far-periphery of diabetic patients by Shimizu in the 1980's demonstrated areas of peripheral retinal nonperfusion in diabetic patients. These findings have been reproduced and substantiated more recently utilizing a novel, commercially-available imaging system for ultrawide-field angiography (UWFA) that employs a scanning laser ophthalmoscope and an ellipsoidal mirror.
We investigated whether patients with diabetic macular edema associated with peripheral nonperfusion on UWFA would have improved visual acuity, resolution of retinal thickening on OCT, and durability of therapy using a novel strategy of a single intravitreal injection of Ranibizumab, a VEGF-A inhibitor + UWFA-guided peripheral Scatter Laser, or RaScaL. A second goal of the study was to guide DME treatment by the imaging signature of UWFA and OCT.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment group | Experimental | Drug: intravitreal injection of ranibizumab, Procedure: peripheral laser1. single intravitreal injection of ranibizumab (0.5 mg in 0.1 cc) 2. peripheral laser to areas of retinal nonperfusion on ultra-widefield fluorescein angiography |
| Control Group | Active comparator | Drug: intravitreal injection of triamcinolone acetonide, Procedure: macular laser1. single intravitreal injection of triamcinolone acetonide (4.0 mg in 0.1 cc) 2. macular laser per treatment criteria |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Ability to provide written informed consent and comply with study assessments for the full duration of the study
- Age > 18 years
- Patients with Type I or Type II diabetes
- Study eye with clinically significant diabetic macular edema characterized by macular edema, peripheral nonperfusion, and absence of macular traction on clinical exam, UWFA, and OCT.
- Study eye with best corrected visual acuity between 20/40 (≤ 73 letters on Early Treatment of Diabetic Retinopathy Study (ETDRS) chart and 20/320 (≥ 19 letters on ETDRS chart) Other considerations
Key exclusion criteria (12 listed)
- Pregnancy (positive pregnancy test) or lactation. Premenopausal women not using adequate contraception. The following are considered effective means of contraception: surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an Intra Uterine Device, or contraceptive hormone implant or patch.
- Prior enrollment in the study
- Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated
- Participation in another simultaneous medical investigation or trial
- Therapy with intravitreal triamcinolone, pegaptanib, ranibizumab, or bevacizumab within the previous 3 months
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 |
|---|---|---|
| intravitreal injection of ranibizumabAlso: treatment armintravitreal injection of 0.5 mg ranibizumab | Drug | Treatment group |
| peripheral laserAlso: treatment armultra-widefield fluorescein angiography guided peripheral laser | Procedure or surgery | Treatment group |
| intravitreal injection of triamcinolone acetonideAlso: control armintravitreal injection of 4.0 mg triamcinolone acetonide | Drug | Control Group |
| macular laserAlso: control armmacular laser to areas of retinal thickening or leakage | Procedure or surgery | Control Group |
Primary outcome
Mean Change in Best Corrected Visual Acuity (BCVA), as Assessed by the Number of Letters Read Correctly on the ETDRS Eye Chart at a Starting Test Distance of 4 Meters From Baseline to Month 6.
Time frame: 6 months
1 secondary outcome
Mean Central Foveal Thickness (CFT) on Optical Coherence Tomography (OCT) in Microns at 6 Months
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Ivan J Suner, MD principal investigator
Retina Associates of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing intravitreal injection of ranibizumab, peripheral laser and intravitreal injection of triamcinolone acetonide in people with Diabetic Macular Edema, run by Retina Associates of Florida, P.A. 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 10 inclusion and 12 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: finished, as of the sponsor's last update on 5 Mar 2015. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Mar 2015). 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?
Mean Change in Best Corrected Visual Acuity (BCVA), as Assessed by the Number of Letters Read Correctly on the ETDRS Eye Chart at a Starting Test Distance of 4 Meters From Baseline to Month 6. (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Mar 2015.