Center-involved Diabetic Macular Edema, Diabetic Macular Edema
Conditions
Keywords
Diabetic Macular Edema, center-involved diabetic macular edema, Anti-VEGF, Aflibercept, EYLEA, Dapagliflozin, Forxiga, SGLT2 inhibitor
Brief summary
The purpose of this clinical study is to explore the efficacy of dapagliflozin as an adjunct to intravitreal anti-vascular endothelial growth factor (anti-VEGF) for enhanced reduction of retinal thickness and vision improvement in patients with diabetic macular edema. The main question the study aims to answer is: Does dapagliflozin reduce the thickness of the macula when combined with the standard of care intravitreal anti-VEGF therapy more than the intravitreal anti-VEGF therapy alone?
Detailed description
Some evidence in the literature suggests that sodium glucose co-transporter 2 (SGLT2) inhibitors may be beneficial in reducing diabetic macular edema. The objective of this clinical trial is to investigate the efficacy and safety of dapagliflozin when combined with intravitreal aflibercept injections in the management of patients with type II diabetes mellitus and center-involved diabetic macular edema (ci-DME). This randomized, double-blind, parallel group, active control design, clinical trial, is investigating the effect of oral dapagliflozin 10 mg given once daily in addition to intravitreal aflibercept versus intravitreal aflibercept alone on reducing macular central subfield thickness (CST) and improving visual acuity in diabetic patients with ci-DME.
Interventions
DRUGDapagliflozin
Dapagliflozin 10 mg will be given orally once daily for three months.
DRUGAnti-VEGF drug
Aflibercept 2 mg (0.05 ml) will be administered by intravitreal injection every month for three consecutive months.
Sponsors
Alexandria University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Type II diabetes mellitus patients, treated with premixed insulin and metformin, and diagnosed with center-involved diabetic macular edema (CiDME) * Presence of retinal thickening involving the center of the fovea (CiDME) in the study eye on Optical Coherence Tomography (OCT) Heidelberg Spectralis; If both eyes are eligible, the eye with the greater central subfield thickness on OCT is selected as the study eye. * Decreased visual acuity primarily attributable to DME * Clear ocular media and pupillary dilation for adequate retinal imaging * Ability to understand the study procedures and willingness to provide written informed consent Study participant
Exclusion criteria
* Patients below 18 years old and patients above 85 years old * Patients with type I diabetes mellitus (Insulin dependent diabetes mellitus IDDM) * Pregnant women and lactating women diagnosed with diabetes or intending to become pregnant in the next 12 months * Patients who had myocardial infarction within 3 months prior to screening * Patients who had transient ischemic attack (TIA), ischemic or hemorrhagic stroke within 3 months prior to screening * Patients with poorly controlled diabetes mellitus, defined as patients having glycosylated hemoglobin (HbA1c) level of ≥12% at screening or patients who were hospitalized for diabetic ketoacidosis or hyperosmolar coma within 4 months prior to screening * Patients with estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73 m2 at screening * Patients with severe hepatic impairment of Child-Turcotte-Pugh class C at screening * Patients treated with antidiabetic drugs thiazolidinediones (TZD) (rosiglitazone and pioglitazone) prior to screening * Patients who were receiving SGLT2 inhibitors (e.g., dapagliflozin, canagliflozin, or empagliflozin) within 3 months prior to screening * Known allergy or hypersensitivity to any component of the study drugs * Current or previous participation in another clinical study involving the systemic or ocular administration of an investigational drug or device within 6 months of screening Study eye
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean central subfield thickness (CST) | Baseline, 3 months | The reduction in mean central subfield thickness (CST) from baseline will be determined using Optical Coherence Tomography (OCT) and compared between study groups. |
| The best-corrected visual acuity (BCVA) | Baseline, 3 months | The improvement in the best-corrected visual acuity (BCVA) from baseline will be recorded and compared between study groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Visual impairment patient reported outcome | Baseline, 3 months | Patient reported outcome measures for visual impairment will be reported at baseline and after receiving interventions, using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25), and compared across study groups. |
| Percentage of patients with persistent macular edema | 3 months | The number of patients with persistent macular edema who are indicated to continue intravitreal anti-VEGF therapy beyond the initial 3 injections will be compared across study groups. |
| Measuring the levels of some inflammatory cytokines in the aqueous humor | Baseline, 2 months | The routinely withdrawn aqueous humor samples from patients with DME during intravitreal anti-VEGF injection will be collected and analyzed. The levels of inflammatory cytokines VEGF-A, interleukin (IL)-6, monocyte chemoattractant protein 1 (MCP-1), and tumor necrosis factor (TNF)-α, will be quantified, using multiplex protein analysis, and compared between the study groups. |
| Incidence of adverse events | 3 months | Systemic and ocular adverse events will be recorded and compared across study groups to assess the safety profile of the interventions. |
| Retinal anatomical changes | Baseline, 3 months | Retinal anatomical changes such as the improvement of cystoid macular spaces and resolution of subretinal fluid will be determined on OCT. |
Countries
Egypt
Contacts
Primary ContactAmira A. Nayel, Pharm.D, MSc
Outcome results
None listed