Ignite Creation Date:
2024-05-06 @ 3:46 PM
Last Modification Date:
2024-10-26 @ 1:57 PM
Study NCT ID:
NCT04756310
Status:
COMPLETED
Last Update Posted:
2021-02-16
First Post:
2015-12-04
Brief Title:
Study of Nutritional Supplementation in Patients With Unilateral Wet AMD
Sponsor:
Laboratorios Thea Spain
Organization:
Laboratorios Thea Spain
Study Overview
Official Title:
A Randomized Multicenter Interventional Study of Nutritional Supplementation in Patients With Unilateral Wet AMD
Status:
COMPLETED
Status Verified Date:
2021-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Retinal diseases are currently the leading cause of legal blindness in the developed world Among these disorders age-related macular degeneration AMD is one of the most prevalent conditions in individuals over 55 years of age Late AMD the most severe presentation of the disease clinically manifests as either geographic atrophy dry form or choroidal neovascularization CNV wet form Although patients with wet AMD only represent 10 of the total cases CNV is the main and most serious cause of central vision loss At present the treatment of wet AMD comprises intraocular injections of certain antiangiogenic agents which act by blocking VEGF vascular endothelial growth factor No effective treatment is yet available for dry AMD though the AREDS Age-Related Eye Disease Study has shown that the administration of antioxidant supplements is able to slow progression of the disease Such vitamin supplements are also indicated in patients who already have severe AMD both exudative and atrophic in one eye since the risk of progression in these cases is high
Recent studies involving new antioxidant and antiangiogenic molecules such as resveratrol present in grapes and wine have also revealed great efficacy in slowing the progression of advanced AMD Hydroxytyrosol is another polyphenol with important antioxidant and antiinflammatory effects in the RPE
Considering the above the present randomized multicenter interventional study involving Spanish and Portuguese patients with unilateral wet AMD was designed to compare the effects of two different nutritional supplements one containing the antioxidants and minerals recommended by the AREDS at doses that can be used in the European Union Theavit and the other comprising these same substances plus omega-3 fatty acids lipidic antioxidant lutein pigment protecting against light-induced damage and resveratrol antioxidant and antiangiogenic agent Retilut
Recent studies involving new antioxidant and antiangiogenic molecules such as resveratrol present in grapes and wine have also revealed great efficacy in slowing the progression of advanced AMD Hydroxytyrosol is another polyphenol with important antioxidant and antiinflammatory effects in the RPE
Considering the above the present randomized multicenter interventional study involving Spanish and Portuguese patients with unilateral wet AMD was designed to compare the effects of two different nutritional supplements one containing the antioxidants and minerals recommended by the AREDS at doses that can be used in the European Union Theavit and the other comprising these same substances plus omega-3 fatty acids lipidic antioxidant lutein pigment protecting against light-induced damage and resveratrol antioxidant and antiangiogenic agent Retilut
Detailed Description:
Retinal diseases are currently the leading cause of legal blindness in the developed world Among these disorders age-related macular degeneration AMD is one of the most prevalent conditions in individuals over 55 years of age In the United States the prevalence of AMD varies from 05 at 55 years to 7 in people over 75 years These data are clearly a cause for concern in view of the aging of the population in developed countries In Spain a country with one of the greatest population aging problems AMD affects 17 of all people over 50 years and the incidence increases with age reaching 185 among those over 85 years AMD is characterized by progressive destruction of the central region of the retina macula resulting in central vision loss While this does not lead to complete blindness the associated impairment of autonomy has a very strong impact upon patient quality of life AMD is a multifactorial disease - a fact that makes it difficult to establish the underlying etiology In this sense although only age is accepted as the principal factor associated to the development of AMD other factors such as smoking diet oxidative stress arterial hypertension or obesity have been extensively investigated in the context of the disease
Late AMD the most severe presentation of the disease clinically manifests as either geographic atrophy dry form or choroidal neovascularization CNV wet form Although patients with wet AMD only represent 10 of the total cases CNV is the main and most serious cause of central vision loss At present the treatment of wet AMD comprises intraocular injections of certain antiangiogenic agents such as ranibizumab bevacizumab aflibercept etc which act by blocking vascular endothelial growth factor VEGF No effective treatment is yet available for dry AMD though the Age-Related Eye Disease Study AREDS has shown that the administration of antioxidant supplements is able to slow progression of the disease Such vitamin supplements are also indicated in patients who already have severe AMD both exudative and atrophic in one eye since the risk of progression in these cases is high
The AREDS sponsored by the National Eye Institute was started in 1998 with the purpose of evaluating the effect of high-dose antioxidants vitamins C and E and beta-carotene and minerals zinc upon the course of the disease The results of the study showed that high levels of antioxidants and zinc significantly reduced the risk of progression towards advanced stages of AMD by 25 and of vision loss by 19 However due to safety reasons the doses used in the AREDS cannot be administered in the European Union since they exceed the Recommended Daily Allowances RDA Therefore the standard clinical practice is to use these substances in patients with high risk AMD as nutritional supplements at the usual RDAs However no interventional studies demonstrating the effects of these supplements have been carried out
Following publication of the AREDS I certain dietary intake studies suggested the importance of other molecules such as omega-3 fatty acids DHA EPA DPA and lutein zeaxanthin The AREDS work group therefore decided to conduct a new study including both nutrients in addition to those already evaluated antioxidants and zinc Lutein exerts an antioxidative effect can act as a blue light filter and moreover has antiinflammatory properties This latter effect is especially important considering that AMD is a disease secondary to a low-grade chronic inflammatory process of the retinal pigment epithelium RPE In addition to their antioxidant and antiinflammatory effects the omega-3 fatty acids have important antiangiogenic properties as evidenced both by in vitro and in vivo studies
Recent studies involving new antioxidant and antiangiogenic molecules such as resveratrol present in grapes and wine have also revealed great efficacy in slowing the progression of advanced AMD Hydroxytyrosol is another polyphenol with important antioxidant and antiinflammatory effects in the RPE
Considering the above the present randomized multicenter interventional study involving Spanish and Portuguese patients with unilateral wet AMD was designed to compare the effects of two different nutritional supplements one containing the antioxidants and minerals recommended by the AREDS at doses that can be used in the European Union Theavit and the other comprising these same substances plus omega-3 fatty acids lipidic antioxidant lutein pigment protecting against light-induced damage and resveratrol antioxidant and antiangiogenic agent Retilut
Study Design A randomized double-blind multicenter interventional nutritional dose study was designed The patient follow-up period will last 24 months The estimated patient enrollment period will cover 9 months and analysis of the results will be completed four months after the end of the follow-up period The estimated total duration of the project will be between 52 months
Study Subjects
These patients from the different Spanish populations will be enrolled making use of the infrastructure afforded by the RETICS network Eye disease related to aging vision quality and quality of life RD070062 subproject Retina All patients will be 50 years old or more and written informed consent will be obtained in all cases together with authorization to enter their data in a database data protection consent following the criteria of the Ethics Committees of each of the participating centers
On the baseline visit the patients will undergo a complete ophthalmological evaluation and plasma will be collected for posterior analysis of several biochemical parameters
Those patients who meet the inclusion criteria and none of the exclusion criteria will start nutritional supplementation for two years 2 daily capsule nutritional dose with one of the nutritional supplements The study will be carried out on a simple-blind basis even the patient knows the origin of the treatment the ophthalmologist conducting follow-up will not know the composition of the provided supplement Accordingly the boxes and capsules will be adequately masked The blisters with the nutritional supplements will be delivered to each patient at the inclusión visit Day 0 and the empty blisters are to be returned as an initial measure of treatment compliance Patient follow-up will take place every 6 months Day 0 Month 6 Month 12 Month 18 Month 24 and will comprise a complete ophthalmological evaluation with the registry of any ophthalmological adverse events The appearance of such adverse events will be a secondary study endpoint and is defined as the appearance of choroidal neovascularization in the fellow eye First objective will be the measure of the change in the best corrected visual acuity BCVA in the study eye Blood samples will be collected at Day 0 Month 12 and Month 24 for biochemical analysis Luminex markers omega 3 lutein and zeaxanthin profile and plasma REDOX status representing also a secondary study endpoints
Ophthalmological examination
Visual acuity will be determined with the ETDRS system at a distance of four meters with the best optic correction
Anterior segment biomicroscopy study to discard opacification of the media -Biomicroscopic funduscopy with 7890D lens
Digital retinography of the ocular fundus red-free light photography of the fundus and autofluorescence photography of the fundus under maximum pharmacologic mydriasis to ensure maximum image quality a minimum of three examinations with photographs at 3035 will be obtained
The follow-up of neovascularization will be carried out by fluorescein angiography and optical coherence tomography OCT The presence of subretinal andor intraretinal fluid will be taken as a sign of wet AMD in OCT
Biochemical analysis
The plasma of the patients both on Day 0 and at the end of the study will be subjected to the following determinations
Analysis of the lipid profile omega 3
Evaluation of the systemic oxidative condition based on total antioxidant capacity assay
Determination of lutein levels by HPLC
Detection of the main inflammatory and oxidative stress markers andor vascular factors in plasma based on Luminex technology affymetrix VEGF-A IL-1 beta IL-6 IL-8 Eotaxin-2 CCL24 HGF PDGF MCP-1 TNF-alpha and FGF
Late AMD the most severe presentation of the disease clinically manifests as either geographic atrophy dry form or choroidal neovascularization CNV wet form Although patients with wet AMD only represent 10 of the total cases CNV is the main and most serious cause of central vision loss At present the treatment of wet AMD comprises intraocular injections of certain antiangiogenic agents such as ranibizumab bevacizumab aflibercept etc which act by blocking vascular endothelial growth factor VEGF No effective treatment is yet available for dry AMD though the Age-Related Eye Disease Study AREDS has shown that the administration of antioxidant supplements is able to slow progression of the disease Such vitamin supplements are also indicated in patients who already have severe AMD both exudative and atrophic in one eye since the risk of progression in these cases is high
The AREDS sponsored by the National Eye Institute was started in 1998 with the purpose of evaluating the effect of high-dose antioxidants vitamins C and E and beta-carotene and minerals zinc upon the course of the disease The results of the study showed that high levels of antioxidants and zinc significantly reduced the risk of progression towards advanced stages of AMD by 25 and of vision loss by 19 However due to safety reasons the doses used in the AREDS cannot be administered in the European Union since they exceed the Recommended Daily Allowances RDA Therefore the standard clinical practice is to use these substances in patients with high risk AMD as nutritional supplements at the usual RDAs However no interventional studies demonstrating the effects of these supplements have been carried out
Following publication of the AREDS I certain dietary intake studies suggested the importance of other molecules such as omega-3 fatty acids DHA EPA DPA and lutein zeaxanthin The AREDS work group therefore decided to conduct a new study including both nutrients in addition to those already evaluated antioxidants and zinc Lutein exerts an antioxidative effect can act as a blue light filter and moreover has antiinflammatory properties This latter effect is especially important considering that AMD is a disease secondary to a low-grade chronic inflammatory process of the retinal pigment epithelium RPE In addition to their antioxidant and antiinflammatory effects the omega-3 fatty acids have important antiangiogenic properties as evidenced both by in vitro and in vivo studies
Recent studies involving new antioxidant and antiangiogenic molecules such as resveratrol present in grapes and wine have also revealed great efficacy in slowing the progression of advanced AMD Hydroxytyrosol is another polyphenol with important antioxidant and antiinflammatory effects in the RPE
Considering the above the present randomized multicenter interventional study involving Spanish and Portuguese patients with unilateral wet AMD was designed to compare the effects of two different nutritional supplements one containing the antioxidants and minerals recommended by the AREDS at doses that can be used in the European Union Theavit and the other comprising these same substances plus omega-3 fatty acids lipidic antioxidant lutein pigment protecting against light-induced damage and resveratrol antioxidant and antiangiogenic agent Retilut
Study Design A randomized double-blind multicenter interventional nutritional dose study was designed The patient follow-up period will last 24 months The estimated patient enrollment period will cover 9 months and analysis of the results will be completed four months after the end of the follow-up period The estimated total duration of the project will be between 52 months
Study Subjects
These patients from the different Spanish populations will be enrolled making use of the infrastructure afforded by the RETICS network Eye disease related to aging vision quality and quality of life RD070062 subproject Retina All patients will be 50 years old or more and written informed consent will be obtained in all cases together with authorization to enter their data in a database data protection consent following the criteria of the Ethics Committees of each of the participating centers
On the baseline visit the patients will undergo a complete ophthalmological evaluation and plasma will be collected for posterior analysis of several biochemical parameters
Those patients who meet the inclusion criteria and none of the exclusion criteria will start nutritional supplementation for two years 2 daily capsule nutritional dose with one of the nutritional supplements The study will be carried out on a simple-blind basis even the patient knows the origin of the treatment the ophthalmologist conducting follow-up will not know the composition of the provided supplement Accordingly the boxes and capsules will be adequately masked The blisters with the nutritional supplements will be delivered to each patient at the inclusión visit Day 0 and the empty blisters are to be returned as an initial measure of treatment compliance Patient follow-up will take place every 6 months Day 0 Month 6 Month 12 Month 18 Month 24 and will comprise a complete ophthalmological evaluation with the registry of any ophthalmological adverse events The appearance of such adverse events will be a secondary study endpoint and is defined as the appearance of choroidal neovascularization in the fellow eye First objective will be the measure of the change in the best corrected visual acuity BCVA in the study eye Blood samples will be collected at Day 0 Month 12 and Month 24 for biochemical analysis Luminex markers omega 3 lutein and zeaxanthin profile and plasma REDOX status representing also a secondary study endpoints
Ophthalmological examination
Visual acuity will be determined with the ETDRS system at a distance of four meters with the best optic correction
Anterior segment biomicroscopy study to discard opacification of the media -Biomicroscopic funduscopy with 7890D lens
Digital retinography of the ocular fundus red-free light photography of the fundus and autofluorescence photography of the fundus under maximum pharmacologic mydriasis to ensure maximum image quality a minimum of three examinations with photographs at 3035 will be obtained
The follow-up of neovascularization will be carried out by fluorescein angiography and optical coherence tomography OCT The presence of subretinal andor intraretinal fluid will be taken as a sign of wet AMD in OCT
Biochemical analysis
The plasma of the patients both on Day 0 and at the end of the study will be subjected to the following determinations
Analysis of the lipid profile omega 3
Evaluation of the systemic oxidative condition based on total antioxidant capacity assay
Determination of lutein levels by HPLC
Detection of the main inflammatory and oxidative stress markers andor vascular factors in plasma based on Luminex technology affymetrix VEGF-A IL-1 beta IL-6 IL-8 Eotaxin-2 CCL24 HGF PDGF MCP-1 TNF-alpha and FGF
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