Ignite Creation Date:
2024-05-05 @ 6:34 PM
Last Modification Date:
2024-10-26 @ 9:34 AM
Study NCT ID:
NCT00500396
Status:
TERMINATED
Last Update Posted:
2024-05-30
First Post:
2007-07-10
Brief Title:
Vascular Endothelial Growth Factor in Stage V ROP
Sponsor:
Asociación para Evitar la Ceguera en México
Organization:
Asociación para Evitar la Ceguera en México
Study Overview
Official Title:
Vascular Endothelial Growth Factor Levels in Aqueous Vitreous and Subretinal Fluid in Patients With Retinopathy of Prematurity Stage V
Status:
TERMINATED
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Undefined
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Vascular Endothelial Growth Factor VEGF is a dimeric glycoprotein naturally expressed in epithelial and tumor cells 1 Normal Retinal vascularization has two phases In the first fase cells of mesenquimatous origin form the first superficial plexus 14-21 weeks of gestation In the second phase denominated angiogenesis phase the superficial and deep capillary plexus are formed 1520 The Retinopathy of Prematurity ROP was described for the first time in 1942 4 at the present moment it is a public health problem in the developing countries The International Classification of ROP classifies it in 5 stages dividing it in 3 anatomical zones It is a public health problem that continuous without having an effective prophylaxis The early diagnosis and treatment in thresholds stages have changed the prognosis of this disease 1112
Detailed Description:
Vascular Endothelial Growth Factor VEGF is a dimeric glycoprotein naturally expressed in epithelial and tumor cells 1 In conditions of hypoxia it is secreted by the pericytes the Retina Pigmented epithelium RPEand glial cells including a the Müller cells 1245 favoring the formation of new abnormal vessels 1 Its activity is mediated by two high affinity receptors the receptor VEGF 1 FLT-1 and VEGF 2 FLT-2 19 The FLT-1 promotes cellular proliferation whereas FLT-2 the migration and cell- extracellular matrix interaction 9 The VEGF is essential as much for the normal retinal vascularization as for pathological 514
Normal Retinal vascularization has two phases In the first fase cells of mesenquimatous origin form the first superficial plexus 14-21 weeks of gestation In the second phase denominated angiogenesis phase the superficial and deep capillary plexus are formed 1520 The second phase is highly dependent of VEGF induced by hypoxia 1520 In the normal retina the growth occurs from the optical nerve to the periphery 17
The scientific progress in the neonatal intensive care units in the last years has allowed the survival of a larger number of premature newborns15
The Retinopathy of Prematurity ROPROP was described for the first time in 1942 4 at the present moment it is a public health problem in the developing countries Of each 100000 blind child in Latin America 24000 are due to ROP 2401000 blind child 17 It is the main cause of blindness in premature new born 145 It is of multifactorial etiology 17 but it has been related to a short gestational age smaller to 32 weeks of gestation 4 to low birth weight less of 1500gr or very low birth weight less 1250gr145171820 to the administration of high oxygen concentration immediately after birth 1318 low levels of the Insulin-like growth factorIGF-I and excessive production of VEGF 317
All this combined with large periods of hyperoxia-hypoxia Produces that the normal vascularization of the retina stops This also produces vascular-occlusive changes arteriovenous anastomoses in the edge of the vascularized with the none-vascularized retina 18 begins the formation of abnormal vessels towards the vitreous finally lead to retina detachment in the most severe cases 2345
The International Classification of ROP classifies it in 5 stages dividing it in 3 anatomical zones A threshold stage is considered when we have the presence of stage 3 in zone 1 or 2 in 5 continuous hour uses or 8 discontinuous with plus disease 151617 The pre-threshold stage is divided in two types type 1 is any stage of the disease in zone 1 with plus disease stage 3 without plus disease in zone 1 or stage 2 or 3 with plus in zone 2 Type 2 is stage 1 or 2 without plus disease in zone 1 or stage 3 without plus disease in zone 2 1719 The threshold stage happens approximately in 5 of the patients with very low weight to the birth of which the 10-15 develop blindness 68
It is a public health problem that continuous without having an effective prophylaxis 5 nevertheless the use of constant oxygen concentrations avoiding the periods of hyperoxia-hypoxia has demonstrated to produce a decrease of the presentation of advanced stages of the disease and the necessity of ophthalmological surgery 5 The early diagnosis and treatment in thresholds stages have changed the prognosis of this disease 1112 The use of the laser as treatment in the threshold and prethreshold stages is successful in the 91-95 of the cases10 the ablative effect on the neurons probably diminishes the VEGF production 15 The use of the vitrectomy in the early cases of retinal detachment also has good results 13
For the determination and the quantification of VEGF several laboratory techniques have been used as they are the Westernblot 1 the flow cytometry 7 CBA 7 Nevertheless the Enzyme-linked immunoabsorbent assay ELISA remains the gold standard for the measurement of interleukins growth factors and other cytokines in corporal fluids including the vitreous aqueous and subretinal fluid 157
It has been demonstrated in humans that there are high vitreous concentrations of VEGF in eyes with active neovascularization 614 In the same way the animal models of ROP report high levels of VEGF 221 The levels of this growth factor are altered in both stages with a more marked increase during the first stage 2 Some clinical studies in patients with ROP in stage 4 and 5 have reported an increase of up to 90 times greater of the concentration of VEGF in the subretinal liquid in comparison with the found in patients with retinal detachment of any other cause 1 Finally when it has been possible to examine retinas immediately after the treatment due to death of the patient have been found a low expression of mRNA of VEGF in the treated cells 6
Normal Retinal vascularization has two phases In the first fase cells of mesenquimatous origin form the first superficial plexus 14-21 weeks of gestation In the second phase denominated angiogenesis phase the superficial and deep capillary plexus are formed 1520 The second phase is highly dependent of VEGF induced by hypoxia 1520 In the normal retina the growth occurs from the optical nerve to the periphery 17
The scientific progress in the neonatal intensive care units in the last years has allowed the survival of a larger number of premature newborns15
The Retinopathy of Prematurity ROPROP was described for the first time in 1942 4 at the present moment it is a public health problem in the developing countries Of each 100000 blind child in Latin America 24000 are due to ROP 2401000 blind child 17 It is the main cause of blindness in premature new born 145 It is of multifactorial etiology 17 but it has been related to a short gestational age smaller to 32 weeks of gestation 4 to low birth weight less of 1500gr or very low birth weight less 1250gr145171820 to the administration of high oxygen concentration immediately after birth 1318 low levels of the Insulin-like growth factorIGF-I and excessive production of VEGF 317
All this combined with large periods of hyperoxia-hypoxia Produces that the normal vascularization of the retina stops This also produces vascular-occlusive changes arteriovenous anastomoses in the edge of the vascularized with the none-vascularized retina 18 begins the formation of abnormal vessels towards the vitreous finally lead to retina detachment in the most severe cases 2345
The International Classification of ROP classifies it in 5 stages dividing it in 3 anatomical zones A threshold stage is considered when we have the presence of stage 3 in zone 1 or 2 in 5 continuous hour uses or 8 discontinuous with plus disease 151617 The pre-threshold stage is divided in two types type 1 is any stage of the disease in zone 1 with plus disease stage 3 without plus disease in zone 1 or stage 2 or 3 with plus in zone 2 Type 2 is stage 1 or 2 without plus disease in zone 1 or stage 3 without plus disease in zone 2 1719 The threshold stage happens approximately in 5 of the patients with very low weight to the birth of which the 10-15 develop blindness 68
It is a public health problem that continuous without having an effective prophylaxis 5 nevertheless the use of constant oxygen concentrations avoiding the periods of hyperoxia-hypoxia has demonstrated to produce a decrease of the presentation of advanced stages of the disease and the necessity of ophthalmological surgery 5 The early diagnosis and treatment in thresholds stages have changed the prognosis of this disease 1112 The use of the laser as treatment in the threshold and prethreshold stages is successful in the 91-95 of the cases10 the ablative effect on the neurons probably diminishes the VEGF production 15 The use of the vitrectomy in the early cases of retinal detachment also has good results 13
For the determination and the quantification of VEGF several laboratory techniques have been used as they are the Westernblot 1 the flow cytometry 7 CBA 7 Nevertheless the Enzyme-linked immunoabsorbent assay ELISA remains the gold standard for the measurement of interleukins growth factors and other cytokines in corporal fluids including the vitreous aqueous and subretinal fluid 157
It has been demonstrated in humans that there are high vitreous concentrations of VEGF in eyes with active neovascularization 614 In the same way the animal models of ROP report high levels of VEGF 221 The levels of this growth factor are altered in both stages with a more marked increase during the first stage 2 Some clinical studies in patients with ROP in stage 4 and 5 have reported an increase of up to 90 times greater of the concentration of VEGF in the subretinal liquid in comparison with the found in patients with retinal detachment of any other cause 1 Finally when it has been possible to examine retinas immediately after the treatment due to death of the patient have been found a low expression of mRNA of VEGF in the treated cells 6
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None