Basis and Design of a Randomized Clinical Trial to Evaluate the Effect of Levosulpiride on Retinal Alterations in Patients With Diabetic Retinopathy and Diabetic Macular Edema
BackgroundDiabetic retinopathy (DR) and diabetic macular edema (DME) are potentially blinding, microvascular retinal diseases in people with diabetes mellitus. Preclinical studies support a protective role of the hormone prolactin (PRL) due to its ocular incorporation and conversion to vasoinhibins,...
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| Format: | Article |
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Frontiers Media S.A.
2018-05-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fendo.2018.00242/full |
| _version_ | 1819277090961227776 |
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| author | Ma. Ludivina Robles-Osorio Renata García-Franco Carlos D. Núñez-Amaro Ximena Mira-Lorenzo Paulina Ramírez-Neria Wendy Hernández Ellery López-Star Thomas Bertsch Gonzalo Martínez de la Escalera Jakob Triebel Carmen Clapp |
| author_facet | Ma. Ludivina Robles-Osorio Renata García-Franco Carlos D. Núñez-Amaro Ximena Mira-Lorenzo Paulina Ramírez-Neria Wendy Hernández Ellery López-Star Thomas Bertsch Gonzalo Martínez de la Escalera Jakob Triebel Carmen Clapp |
| author_sort | Ma. Ludivina Robles-Osorio |
| collection | DOAJ |
| description | BackgroundDiabetic retinopathy (DR) and diabetic macular edema (DME) are potentially blinding, microvascular retinal diseases in people with diabetes mellitus. Preclinical studies support a protective role of the hormone prolactin (PRL) due to its ocular incorporation and conversion to vasoinhibins, a family of PRL fragments that inhibit ischemia-induced retinal angiogenesis and diabetes-derived retinal vasopermeability. Here, we describe the protocol of an ongoing clinical trial investigating a new therapy for DR and DME based on elevating the circulating levels of PRL with the prokinetic, dopamine D2 receptor blocker, levosulpiride.MethodsIt is a prospective, randomized, double-blind, placebo-controlled trial enrolling male and female patients with type 2 diabetes having DME, non-proliferative DR (NPDR), proliferative DR (PDR) requiring vitrectomy, and DME plus standard intravitreal therapy with the antiangiogenic agent, ranibizumab. Patients are randomized to receive placebo (lactose pill, orally TID) or levosulpiride (75 mg/day orally TID) for 8 weeks (DME and NPDR), 1 week (the period before vitrectomy in PDR), or 12 weeks (DME plus ranibizumab). In all cases the study medication is taken on top of standard therapy for diabetes, blood pressure control, or other medical conditions. Primary endpoints in groups 1 and 2 (DME: placebo and levosulpiride), groups 3 and 4 (NPDR: placebo and levosulpiride), and groups 7 and 8 (DME plus ranibizumab: placebo and levosulpiride) are changes from baseline in visual acuity, retinal thickness assessed by optical coherence tomography, and retinal microvascular abnormalities evaluated by fundus biomicroscopy and fluorescein angiography. Changes in serum PRL levels and of PRL and vasoinhibins levels in the vitreous between groups 5 and 6 (PDR undergoing vitrectomy: placebo and levosulpiride) serve as proof of principle that PRL enters the eye to counteract disease progression. Secondary endpoints are changes during the follow-up of health and metabolic parameters (blood pressure, glycated hemoglobin, and serum levels of glucose and creatinine). A total of 120 patients are being recruited.DiscussionThis trial will provide important knowledge on the potential benefits and safety of elevating circulating and intraocular PRL levels with levosulpiride in patients with DR and DME.Ethics and disseminationEthics approval has been obtained from the Ethics Committees of the National University of Mexico (UNAM) and the Instituto Mexicano de Oftalmología, I.A.P. Dissemination will include submission to peer-reviewed scientific journals and presentation at congresses.Clinical trial registrationRegistered at www.ClinicalTrials.gov, ID: NCT03161652 on May 18, 2017. |
| first_indexed | 2024-12-23T23:50:36Z |
| format | Article |
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| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-23T23:50:36Z |
| publishDate | 2018-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-746ff60147bb43f69a7319253c12df2c2022-12-21T17:25:24ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922018-05-01910.3389/fendo.2018.00242352003Basis and Design of a Randomized Clinical Trial to Evaluate the Effect of Levosulpiride on Retinal Alterations in Patients With Diabetic Retinopathy and Diabetic Macular EdemaMa. Ludivina Robles-Osorio0Renata García-Franco1Carlos D. Núñez-Amaro2Ximena Mira-Lorenzo3Paulina Ramírez-Neria4Wendy Hernández5Ellery López-Star6Thomas Bertsch7Gonzalo Martínez de la Escalera8Jakob Triebel9Carmen Clapp10Facultad de Ciencias Naturales, Universidad Autónoma de Querétaro (UAQ), Querétaro, MexicoInstituto Mexicano de Oftalmología, I.A.P., Querétaro, MexicoFacultad de Ciencias Naturales, Universidad Autónoma de Querétaro (UAQ), Querétaro, MexicoInstituto Mexicano de Oftalmología, I.A.P., Querétaro, MexicoInstituto Mexicano de Oftalmología, I.A.P., Querétaro, MexicoInstituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Querétaro, MexicoInstituto Mexicano de Oftalmología, I.A.P., Querétaro, MexicoInstitute for Clinical Chemistry, Laboratory Medicine and Transfusion Medicine, Nuremberg General Hospital & Paracelsus Medical University, Nuremberg, GermanyInstituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Querétaro, MexicoInstitute for Clinical Chemistry, Laboratory Medicine and Transfusion Medicine, Nuremberg General Hospital & Paracelsus Medical University, Nuremberg, GermanyInstituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Querétaro, MexicoBackgroundDiabetic retinopathy (DR) and diabetic macular edema (DME) are potentially blinding, microvascular retinal diseases in people with diabetes mellitus. Preclinical studies support a protective role of the hormone prolactin (PRL) due to its ocular incorporation and conversion to vasoinhibins, a family of PRL fragments that inhibit ischemia-induced retinal angiogenesis and diabetes-derived retinal vasopermeability. Here, we describe the protocol of an ongoing clinical trial investigating a new therapy for DR and DME based on elevating the circulating levels of PRL with the prokinetic, dopamine D2 receptor blocker, levosulpiride.MethodsIt is a prospective, randomized, double-blind, placebo-controlled trial enrolling male and female patients with type 2 diabetes having DME, non-proliferative DR (NPDR), proliferative DR (PDR) requiring vitrectomy, and DME plus standard intravitreal therapy with the antiangiogenic agent, ranibizumab. Patients are randomized to receive placebo (lactose pill, orally TID) or levosulpiride (75 mg/day orally TID) for 8 weeks (DME and NPDR), 1 week (the period before vitrectomy in PDR), or 12 weeks (DME plus ranibizumab). In all cases the study medication is taken on top of standard therapy for diabetes, blood pressure control, or other medical conditions. Primary endpoints in groups 1 and 2 (DME: placebo and levosulpiride), groups 3 and 4 (NPDR: placebo and levosulpiride), and groups 7 and 8 (DME plus ranibizumab: placebo and levosulpiride) are changes from baseline in visual acuity, retinal thickness assessed by optical coherence tomography, and retinal microvascular abnormalities evaluated by fundus biomicroscopy and fluorescein angiography. Changes in serum PRL levels and of PRL and vasoinhibins levels in the vitreous between groups 5 and 6 (PDR undergoing vitrectomy: placebo and levosulpiride) serve as proof of principle that PRL enters the eye to counteract disease progression. Secondary endpoints are changes during the follow-up of health and metabolic parameters (blood pressure, glycated hemoglobin, and serum levels of glucose and creatinine). A total of 120 patients are being recruited.DiscussionThis trial will provide important knowledge on the potential benefits and safety of elevating circulating and intraocular PRL levels with levosulpiride in patients with DR and DME.Ethics and disseminationEthics approval has been obtained from the Ethics Committees of the National University of Mexico (UNAM) and the Instituto Mexicano de Oftalmología, I.A.P. Dissemination will include submission to peer-reviewed scientific journals and presentation at congresses.Clinical trial registrationRegistered at www.ClinicalTrials.gov, ID: NCT03161652 on May 18, 2017.https://www.frontiersin.org/article/10.3389/fendo.2018.00242/fulldopamine receptor type 2 blockersprolactinvasoinhibinsranibizumabretinamicrovascular alterations |
| spellingShingle | Ma. Ludivina Robles-Osorio Renata García-Franco Carlos D. Núñez-Amaro Ximena Mira-Lorenzo Paulina Ramírez-Neria Wendy Hernández Ellery López-Star Thomas Bertsch Gonzalo Martínez de la Escalera Jakob Triebel Carmen Clapp Basis and Design of a Randomized Clinical Trial to Evaluate the Effect of Levosulpiride on Retinal Alterations in Patients With Diabetic Retinopathy and Diabetic Macular Edema Frontiers in Endocrinology dopamine receptor type 2 blockers prolactin vasoinhibins ranibizumab retina microvascular alterations |
| title | Basis and Design of a Randomized Clinical Trial to Evaluate the Effect of Levosulpiride on Retinal Alterations in Patients With Diabetic Retinopathy and Diabetic Macular Edema |
| title_full | Basis and Design of a Randomized Clinical Trial to Evaluate the Effect of Levosulpiride on Retinal Alterations in Patients With Diabetic Retinopathy and Diabetic Macular Edema |
| title_fullStr | Basis and Design of a Randomized Clinical Trial to Evaluate the Effect of Levosulpiride on Retinal Alterations in Patients With Diabetic Retinopathy and Diabetic Macular Edema |
| title_full_unstemmed | Basis and Design of a Randomized Clinical Trial to Evaluate the Effect of Levosulpiride on Retinal Alterations in Patients With Diabetic Retinopathy and Diabetic Macular Edema |
| title_short | Basis and Design of a Randomized Clinical Trial to Evaluate the Effect of Levosulpiride on Retinal Alterations in Patients With Diabetic Retinopathy and Diabetic Macular Edema |
| title_sort | basis and design of a randomized clinical trial to evaluate the effect of levosulpiride on retinal alterations in patients with diabetic retinopathy and diabetic macular edema |
| topic | dopamine receptor type 2 blockers prolactin vasoinhibins ranibizumab retina microvascular alterations |
| url | https://www.frontiersin.org/article/10.3389/fendo.2018.00242/full |
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