Diffuse Diabetic Macular EdemaTTDDMENCT01218750
Triple Therapy for Diffuse Diabetic Macular Edema
A study testing Triple therapy for diffuse diabetic macular edema in people with Diffuse Diabetic Macular Edema, run by Military Institute od Medicine National Research Institute at 1 site in Poland.
Trial summary
The purpose of this study is to evaluate the safety end efficacy of combined phakoemulsification and vitrectomy with retinal endophotocoagulation and intraoperative use of bevacizumab in patients with diffuse diabetic macular edema (DDME), to determine the possible preoperative and intraoperative factors that might… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Diffuse Diabetic Macular Edema
- What is being tested?
- Triple therapy for diffuse diabetic macular edema
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 sitePoland
- Study dates
- Dec 2008to Dec 2011
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- diagnosis of DDME on clinical exam, definite retinal thickening involving the center of the macula, confirmed by fluorescein angiography, with or without PVD,
- BCVA of 0,3 or worse in log MAR units (<=70 ETDRS letter) and 1,5 or better in log MAR units (>=10 ETRDS letter),
- mean central macular thickness greater than 250 μm on optic coherence tomography (OCT),
- presence of vitreomacular traction or a thickened and taut posterior hyaloid or presence of an epimacular membrane.
Who cannot join
- significant macular ischemia defined as enlarged perifoveal capillary loss (>1000 µm) by fluorescein angiography,
- the focal macular edema due to focal leakage from microaneurysm,
- ophthalmic disorders associated with macular edema, such as uveitis, branch or central retinal vein occlusion and pseudophakic cystoid macular edema,
- vitreous hemorrhage or tractional retinal detachment secondary to diabetic retinopathy,
- an ocular condition is present such that, visual acuity would not improve from resolution of macular edema (e.g., foveal atrophy, pigmentary abnormalities, dense subfoveal hard exudates),
- history of retinal macular photocoagulation, intravitreal corticosteroids, or other treatment for DME within 3 months prior to enrollment,
- history of any intraocular surgery within prior 6 months.
Trial locations and contacts
1 site in 1 country.
Poland1 site, 1 recruiting
- Recruiting
Military Institute of Medicine
Warsaw, Szaserów 44, 04-141
Kowal Ewelina, (+48) 22 665 707 584, ekowal@wim.mil.pl
Robaszkiewicz Jacek, dr med.
About this study
Official title: Combined Phako-Vitrectomy With ILM Peeling, Retinal Endophotocoagulation, and Intraoperative Use of Bevacizumab for Diffuse Diabetic Macular Edema
The purpose of this study is to evaluate the safety end efficacy of combined phakoemulsification and vitrectomy with retinal endophotocoagulation and intraoperative use of bevacizumab in patients with diffuse diabetic macular edema (DDME), to determine the possible preoperative and intraoperative factors that might influence surgical outcomes.
Read the detailed description
The pathogenesis of the diabetic macular edema is multiple. Therefore treatment of this disease should be combined too. VEGF is involved in pathogenesis of diabetic macular edema and recently anti-VEGF agents such as bevacizumab have been shown to be beneficial in the treatment of this retinal disorder. However, endogenous VEGF is required for visual function. Growing body evidence indicates that VEGF acts also on nonvascular cells, it plays survival role on Muller cells and photoreceptors. Therefore anti-VEGF therapies should be administered with caution and not persistent. Photocoagulation in nonperfused areas eliminate increased production of VEGF, proliferation of RPE and increased production of PEDF in surrounded impact laser area. Vitrectomy with ILM peeling reliefs traction on the macula, improve oxygenation of the macula leading to decreased vascular permeability with subsequent resolution or decrease in DME. Removed ILM contains a part of the Müller cell endfeet and the horizontal gliosis. It is likely that the proliferation of GFAP-stained gliofibrils, observed in microdamaged Müller cells, preserves the blood-retinal barrier, reinforces architectural cohesion, and opposes the installation of the edema. Therefore, we made hypothesis that combined triple therapy was effective for decreasing macular thickness and improvement of vision for eyes with diffuse diabetic macular edema.
It is important for the surgeon to determine the factors that might influence surgical outcome so that patients are chosen for the procedure that they can get benefit from. Therefore, we evaluated the possible preoperative and intraoperative factors that might influence surgical outcomes
- Conditions
- Diffuse Diabetic Macular Edema
- Being tested
- Triple therapy for diffuse diabetic macular edema
- Keywords
- DDME, ppV, ILM peeling, bevacizumab injection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Triple therapy for diffuse diabetic macular edemaProcedure or surgery
Also called Triple Therapy, Avastin (bevacizumab)
Three port pars plana vitrectomy is performed by one surgeon (JR). Induction of PVD is initiated by active suction with the vitrectomy probe over the ONH and continued peripherally. Peeling of the epimacular tissue and ILM is performed by grasping the flap of the ILM with an eckhardts forceps. Trypan Blue is used to stain the ILM. Peripheral laser endophotocoagulation is performed in cases of avascular areas based on FA, active neovascularization, peripheral retinoschisis or retinal breaks. All eyes have a 1,25 mg/0,05 ml bevacizumab injection into vitreous cavity and SF6 gas tamponade at the end of the procedure. Even of absence of cataract formation, a combined procedure is performed because of exactly peripheral vitreous shaving and prevention of cataract formation.
| Study group | Role | What they receive |
|---|---|---|
| edematous tractional epimacular membrane | Experimental | Diabatic maculopathy comes to the edematous or tractional form. It is believed that epiretinal membranes are comprised from glial components. The processes of these cells may invade through the internal limiting membrane of the retina to the vitreous causing the vitreoretinal adhesion and anomalous posterior detachment of vitreous (APVD). In the macula, APVD causes vitreo-macular traction syndrome, which results in diffuse diabetic macular edema. If vitreoschisis is present, a place of dissection is crucial. If break occurs in front of the hyalocytes remaining on the retinal surface, the vitreous layer is thick and easily shrinks concentrically, which results in the formation of epimacular membrane. Receives: Procedure: Triple therapy for diffuse diabetic macular edema |
What is being measured
The primary outcome is the main question the study is designed to answer.
Best-corrected visual acuity (BCVA) and central macular thickness (CMT)
The best corrected visual acuity (BCVA) for ETDRS chart and central macular thickness (CMT) are assessed preoperatively and during the follow-up period. OCT is performed 1 mm and 6 mm diameter topography centered at the patient fixation point. We evaluate mean central retinal thickness and central retinal volume 1 mm and 6 mm in diameter.
Measured: up to 1 week before surgery
Best-corrected visual acuity (BCVA) and central macular thickness (CMT)
The best corrected visual acuity (BCVA) for ETDRS chart, results are converted to log MAR for statistical analysis. The central macular thickness (CMT) are assessed 1 mm diameter topography centered at the patient fixation point for OCT-SLO. We evaluate mean central retinal thickness and central retinal volume 1 mm and 6 mm in diameter.
Measured: 16 up to 17 weeks after surgery
Best-corrected visual acuity (BCVA) and central macular thickness (CMT)
A follow-up examination include: The best corrected visual acuity (BCVA) for ETDRS chart, results are converted to log MAR for statistical analysis. The central macular thickness (CMT) are assessed 1 mm diameter topography centered at the patient fixation point for OCT-SLO. We evaluate mean central retinal thickness and central retinal volume 1 mm and 6 mm in diameter.
Measured: 32 up to 33 weeks after surgery
Best-corrected visual acuity (BCVA) and central macular thickness (CMT)
A follow-up examination include: The best corrected visual acuity (BCVA) for ETDRS chart, results are converted to log MAR for statistical analysis. The central macular thickness (CMT) are assessed 1 mm diameter topography centered at the patient fixation point for OCT-SLO. We evaluate mean central retinal thickness and central retinal volume 1 mm and 6 mm in diameter.
Measured: 48 up to 49 weeks after surgery
Best-corrected visual acuity (BCVA) and central macular thickness (CMT)
A follow-up examination include: The best corrected visual acuity (BCVA) for ETDRS chart, results are converted to log MAR for statistical analysis. The central macular thickness (CMT) are assessed 1 mm diameter topography centered at the patient fixation point for OCT-SLO. We evaluate mean central retinal thickness and central retinal volume 1 mm and 6 mm in diameter.
Measured: 64 up to 65 weeks after surgery
Secondary outcomes (1)
Presence of vitreomacular traction or epimacular membrane, grade of DR, patients age, HbA1c level, BMI, systemic hypertension
The demographic characteristics of the patients including: age, grender, metabolic condition: HbA1c level, body mass index, presence of systemic hypertension, ocular condition: diabetic retinopathy stage, previous laser, presence of viteomacular traction or epiretinal membrane are recorded to eveluate the possible association with chance in postoperative BCVA.
Measured: up to 2 weeks before surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Oct 2010 (estimated)
- Study startDec 2008
- Primary completionDec 2010 (estimated)
- Study completionDec 2011 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diffuse 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
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Military Institute od Medicine National Research Institute
- Sponsor type
- University, hospital or other
- Investigators
- Robaszkiewicz Jacek, dr med., Principal investigator, Department of Ophthalmology Military Institute of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01218750
- Sponsor's protocol ID
- 46/WIM/2008
- Acronym
- TTDDME
- Status last verified
- Sep 2010
- First submitted
- 6 Oct 2010
- Last updated
- 19 Oct 2010
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Robaszkiewicz J, Chmielewska K, Wierzbowska J, Figurska M, Frontczak-Baniewicz M, Stankiewicz A. [Combined surgical and pharmacological treatment of diabetic maculopathy]. Klin Oczna. 2010;112(1-3):19-23. Polish.
PubMed 20572497
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combined Phako-Vitrectomy With ILM Peeling, Retinal Endophotocoagulation, and Intraoperative Use of Bevacizumab for Diffuse Diabetic Macular Edema
- ClinicalTrials.gov ID
- NCT01218750
- Acronym / sponsor ID
- TTDDME / 46/WIM/2008
- Conditions
- Diffuse Diabetic Macular Edema
- Keywords
- DDME, ppV, ILM peeling, bevacizumab injection
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Military Institute od Medicine National Research InstituteUniversity, hospital or other
- Study start
- Dec 2008
- Primary completion
- Dec 2010 (estimated)
- Study completion
- Dec 2011 (estimated)
- First posted
- 11 Oct 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety end efficacy of combined phakoemulsification and vitrectomy with retinal endophotocoagulation and intraoperative use of bevacizumab in patients with diffuse diabetic macular edema (DDME), to determine the possible preoperative and intraoperative factors that might influence surgical outcomes.
Detailed description
The pathogenesis of the diabetic macular edema is multiple. Therefore treatment of this disease should be combined too. VEGF is involved in pathogenesis of diabetic macular edema and recently anti-VEGF agents such as bevacizumab have been shown to be beneficial in the treatment of this retinal disorder. However, endogenous VEGF is required for visual function. Growing body evidence indicates that VEGF acts also on nonvascular cells, it plays survival role on Muller cells and photoreceptors. Therefore anti-VEGF therapies should be administered with caution and not persistent. Photocoagulation in nonperfused areas eliminate increased production of VEGF, proliferation of RPE and increased production of PEDF in surrounded impact laser area. Vitrectomy with ILM peeling reliefs traction on the macula, improve oxygenation of the macula leading to decreased vascular permeability with subsequent resolution or decrease in DME. Removed ILM contains a part of the Müller cell endfeet and the horizontal gliosis. It is likely that the proliferation of GFAP-stained gliofibrils, observed in microdamaged Müller cells, preserves the blood-retinal barrier, reinforces architectural cohesion, and opposes the installation of the edema. Therefore, we made hypothesis that combined triple therapy was effective for decreasing macular thickness and improvement of vision for eyes with diffuse diabetic macular edema.
It is important for the surgeon to determine the factors that might influence surgical outcome so that patients are chosen for the procedure that they can get benefit from. Therefore, we evaluated the possible preoperative and intraoperative factors that might influence surgical outcomes
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| edematous tractional epimacular membrane | Experimental | Procedure: Triple therapy for diffuse diabetic macular edemaDiabatic maculopathy comes to the edematous or tractional form. It is believed that epiretinal membranes are comprised from glial components. The processes of these cells may invade through the internal limiting membrane of the retina to the vitreous causing the vitreoretinal adhesion and anomalous posterior detachment of vitreous (APVD). In the macula, APVD causes vitreo-macular traction syndrome, which results in diffuse diabetic macular edema. If vitreoschisis is present, a place of dissection is crucial. If break occurs in front of the hyalocytes remaining on the retinal surface, the vitreous layer is thick and easily shrinks concentrically, which results in the formation of epimacular membrane. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- diagnosis of DDME on clinical exam, definite retinal thickening involving the center of the macula, confirmed by fluorescein angiography, with or without PVD,
- BCVA of 0,3 or worse in log MAR units (<=70 ETDRS letter) and 1,5 or better in log MAR units (>=10 ETRDS letter),
- mean central macular thickness greater than 250 μm on optic coherence tomography (OCT),
- presence of vitreomacular traction or a thickened and taut posterior hyaloid or presence of an epimacular membrane.
Key exclusion criteria (7 listed)
- significant macular ischemia defined as enlarged perifoveal capillary loss (>1000 µm) by fluorescein angiography,
- the focal macular edema due to focal leakage from microaneurysm,
- ophthalmic disorders associated with macular edema, such as uveitis, branch or central retinal vein occlusion and pseudophakic cystoid macular edema,
- vitreous hemorrhage or tractional retinal detachment secondary to diabetic retinopathy,
- an ocular condition is present such that, visual acuity would not improve from resolution of macular edema (e.g., foveal atrophy, pigmentary abnormalities, dense subfoveal hard exudates),
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 |
|---|---|---|
| Triple therapy for diffuse diabetic macular edemaAlso: Triple Therapy, Avastin (bevacizumab)Three port pars plana vitrectomy is performed by one surgeon (JR). Induction of PVD is initiated by active suction with the vitrectomy probe over the ONH and continued peripherally. Peeling of the epimacular tissue and ILM is performed by grasping the flap of the ILM with an eckhardts forceps. Trypan Blue is used to stain the ILM. Peripheral laser endophotocoagulation is performed in cases of avascular areas based on FA, active neovascularization, peripheral retinoschisis or retinal breaks. All eyes have a 1,25 mg/0,05 ml bevacizumab injection into vitreous cavity and SF6 gas tamponade at the end of the procedure. Even of absence of cataract formation, a combined procedure is performed because of exactly peripheral vitreous shaving and prevention of cataract formation. | Procedure or surgery | edematous tractional epimacular membrane |
Primary outcome
Best-corrected visual acuity (BCVA) and central macular thickness (CMT)
Time frame: up to 1 week before surgery
The best corrected visual acuity (BCVA) for ETDRS chart and central macular thickness (CMT) are assessed preoperatively and during the follow-up period. OCT is performed 1 mm and 6 mm diameter topography centered at the patient fixation point. We evaluate mean central retinal thickness and central retinal volume 1 mm and 6 mm in diameter.
Best-corrected visual acuity (BCVA) and central macular thickness (CMT)
Time frame: 16 up to 17 weeks after surgery
The best corrected visual acuity (BCVA) for ETDRS chart, results are converted to log MAR for statistical analysis. The central macular thickness (CMT) are assessed 1 mm diameter topography centered at the patient fixation point for OCT-SLO. We evaluate mean central retinal thickness and central retinal volume 1 mm and 6 mm in diameter.
Best-corrected visual acuity (BCVA) and central macular thickness (CMT)
Time frame: 32 up to 33 weeks after surgery
A follow-up examination include: The best corrected visual acuity (BCVA) for ETDRS chart, results are converted to log MAR for statistical analysis. The central macular thickness (CMT) are assessed 1 mm diameter topography centered at the patient fixation point for OCT-SLO. We evaluate mean central retinal thickness and central retinal volume 1 mm and 6 mm in diameter.
Best-corrected visual acuity (BCVA) and central macular thickness (CMT)
Time frame: 48 up to 49 weeks after surgery
A follow-up examination include: The best corrected visual acuity (BCVA) for ETDRS chart, results are converted to log MAR for statistical analysis. The central macular thickness (CMT) are assessed 1 mm diameter topography centered at the patient fixation point for OCT-SLO. We evaluate mean central retinal thickness and central retinal volume 1 mm and 6 mm in diameter.
Best-corrected visual acuity (BCVA) and central macular thickness (CMT)
Time frame: 64 up to 65 weeks after surgery
A follow-up examination include: The best corrected visual acuity (BCVA) for ETDRS chart, results are converted to log MAR for statistical analysis. The central macular thickness (CMT) are assessed 1 mm diameter topography centered at the patient fixation point for OCT-SLO. We evaluate mean central retinal thickness and central retinal volume 1 mm and 6 mm in diameter.
1 secondary outcome
Presence of vitreomacular traction or epimacular membrane, grade of DR, patients age, HbA1c level, BMI, systemic hypertension
Time frame: up to 2 weeks before surgery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2010.
- Results publication: PubMed 20572497Robaszkiewicz J, Chmielewska K, Wierzbowska J, Figurska M, Frontczak-Baniewicz M, Stankiewicz A. [Combined surgical and pharmacological treatment of diabetic maculopathy]. Klin Oczna. 2010;112(1-3):19-23. Polish.
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.
Robaszkiewicz Jacek, dr med. principal investigator
Department of Ophthalmology Military Institute of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Triple therapy for diffuse diabetic macular edema in people with Diffuse Diabetic Macular Edema, run by Military Institute od Medicine National Research Institute at 1 site in Poland.
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 4 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 19 Oct 2010. 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 Poland. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Robaszkiewicz Jacek, dr med. (+48604597970, vectra@izet.pl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Best-corrected visual acuity (BCVA) and central macular thickness (CMT) (time frame: up to 1 week before surgery). The study lists 5 primary outcomes in all. 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 NCT01218750, which also lists 1 linked publication.
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 19 Oct 2010.