Recruiting
Phase 2
Effect of Levosulpiride on Retinal Alterations in Patients With Diabetic Retinopathy and Diabetic Macular Edema
Condition(s) studied
Diabetic Macular EdemaDiabetic Retinopathy
Investigational drug(s) / intervention(s)
DME lactose pillDME levosulpirideDR lactose pillDR levosulpirideDR vitrectomy lactose pillDR vitrectomy levosulpirideDME plus ranibizumab lactose pillDME plus ranibizumab levosulpiride
DME lactose pill: Patients with DME will take placebo orally 3 times a day (TID) for 8 weeks.The placebo is taken on top of standard therapy for diabetes and blood pressure control.
DME levosulpiride: Patients with DME will take levosulpiride (75 mg/day) orally TID for 8 weeks. Levosulpiride is taken on top of standard therapy for diabetes and blood pressure control.
DR lactose pill: Patients with non-proliferative DR will take a lactose pill (placebo) orally TID for 8 weeks. The placebo is taken on top of standard therapy for diabetes and blood pressure control.
DR levosulpiride: Patients with non-proliferative DR will take levosulpiride (75 mg/day) orally TIDfor 8 weeks. Levosulpiride is taken on top of standard therapy for diabetes and blood pressure control.
DR vitrectomy lactose pill: Patients with proliferative DR (undergoing medically prescribed vitrectomy 7 days after starting the study medication) will have to take a lactose pill (placebo) orally TID for one week. The last placebo pill will be taken on the morning of the day vitrectomy is performed. The placebo is taken on top of standard therapy for diabetes and blood pressure control.
DR vitrectomy levosulpiride: Patients with proliferative DR (undergoing medically prescribed vitrectomy 7 days after starting the study medication) will take levosulpiride (75 mg/day) orally TID for one week. The last pill will be taken on the morning of the day vitrectomy is performed. Levosulpiride is taken on top of standard therapy for diabetes and blood pressure control.
DME plus ranibizumab lactose pill: Patients with DME with conventional intravitreal antiangiogenic therapy with ranibizumab (0.5 mg every 4 weeks for 12 weeks) will take a lactose pill (placebo) orally TID for 24 weeks. The placebo is taken on top of standard therapy for diabetes and blood pressure control.
DME plus ranibizumab levosulpiride: Patients with DME with receive intravitreal antiangiogenic therapy with ranibizumab (0.5 mg every 4 weeks for 12 weeks) will take a levosulpiride (75 mg/day) orally TID for 24 weeks. The study medication is taken on top of standard therapy for diabetes and blood pressure control.
Study summary
This is a randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of levosulpiride to improve retinal alterations due to diabetic macular edema and diabetic retinopathy
Eligibility
Inclusion Criteria:
* Age equal or greater than 40 years but no older than 69 years
* Male and female subjects with mild and moderate diabetic macular edema (DME), non-proliferative diabetic retinopathy (DR), and with proliferative DR undergoing medically prescribed vitrectomy.
* Signing informed consent
* Without ocular complications: severe myopia (\> 6 diopters), ocular media opacity, retinal detachment, etc.
* Without previous ocular treatments: ocular surgeries, retinal laser photocoagulation, intravitreal administration of antiangiogenic agents (delivered \< 6 months before enrollment).
* Prolactin serum levels ≤ 20 ng/ml
* With normal or mild loss of kidney function (glomerular filtration rate \>60 ml/min) for groups with DME and DR without vitrectomy.
* With mild to severe loss of kidney function (glomerular filtration rate \>30 ml/min) for groups with DR undergoing vitrectomy.
* Without contraindications for the use of levosulpiride (Parkinson disease, epilepsy, breast cancer, alcoholism, hypokalemia).
* Without hyperprolactinemia inducing conditions: Pathologies (hypothyrodism, hepatic dysfunction, prolactinomas); Medication (antipsychotics, antidepressants, prokinetics, other)
Exclusion Criteria:
* Not meeting inclusion criteria.
* Adverse and intolerable drug effects.
* Not complying with study medication
* Inability to continue in-hospital appointments.
* Missing outcome data
* Hesitation to continue with study medication
* Relocation to another state or country
* Voluntary withdrawal of consent
Primary outcome measure(s)
- Visual acuity — 5 minutes
Number of letters recognized in the Early Treatment Diabetic Retinopathy Study (ETDRS) chart test after correcting for any refractive error (myopia, hyperopia, or astigmatism)
- Retinal thickness — Pupils are dilated (eye drops) for 10 to 15 minutes and optical coherence tomography (OCT) images recorded during 5 minutes.
Retinal thickness is evaluated by non-invasive optical coherence tomography (OCT) imaging via qualitative and quantitative analyses. For qualitative analyses, OCT images approaching the histological level of retinal morphology are interpreted based on normal and diseased features (hyper-reflective or hypo-reflective lesions, shadowing, and anatomical changes). Quantitative analysis evaluates retinal reflective signals and their correlation with retinal morphology by computer image-processing algorithms (retinal thickness map, volume, area, 1, 3, and 6 mm ETDRS circle diameters).
- Retinal hard exudates and hemorrhages — Pupils are dilated (eye drops) for 10 to 15 minutes and fundus images recorded during 5 minutes
Number, size, and location of retinal hard exudates and hemorrhages evaluated by indirect ophthalmoscopy
- Retinal microaneurisms, leakage area, cotton-wool spots, venous beading, microvascular and vascular abnormalities — Pupils are dilated (eye drops) for 10 to 15 minutes and fundus images recorded before and at different times (0.5 to 5 minutes) after fluorescein injection.
Location, intensity, and source of above alterations evaluated by fundus fluorescein angiography imaging qualitative and quantitative analysis of hyper-fluorescent or hypo-fluorescent regions.
- Prolactin serum levels — 1-2 minutes (duration of blood withdrawal)
ng/ml levels of prolactin quantified in serum samples using the IMMULITE 2000 XPi immunoassay system
- Prolactin vitreous levels — 2 minutes (duration of vitreous withdrawal during medically prescribed vitrectomy)
ng/ml levels of prolactin quantified in vitreous samples using the IMMULITE 2000 XPi immunoassay system
- Vasoinhibin vitreous levels — 2 minutes (duration of vitreous withdrawal during medically prescribed vitrectomy)
Optical density values of vasoinhibins obtained by the immunoprecipitation-Western blot analysis of vitreous samples
Trial sites (2)
| Facility | City | Region | Status |
|---|
| Instituto Mexicano de Oftalmologia (IMO) |
Querétaro City |
Querétaro |
Recruiting |
| Instituto de la Retina del Bajio SC (INDEREB) |
Querétaro City |
Querétaro |
Recruiting |
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