SNPMiner Trials by Shray Alag


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Report for Mutation Y402H

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 4 clinical trials

Clinical Trials


1 Y402H Comlement Factor H Polymorphism and Age-Related Macular Degeneration in the Austrian Population

The aim of the study is to show a higher expression of the Y402H polymorphism in the complement factor H in patients with AMD compared to healthy individuals. Additionaly a correlation between a subsided infection with chlamydia and patients with AMD and a factor H polymorphism will be investigated. An interrelationship with the VEGF-plasma level shall give more hints into the pathomechanism of AMD.

NCT00533754 Age-Related Macular Degeneration Procedure: drawing blood
MeSH: Macular Degeneration

Y402H Comlement Factor H Polymorphism and Age-Related Macular Degeneration in the Austrian Population. --- Y402H ---

Y402H Comlement Factor H Polymorphism and Age-Related Macular Degeneration in the Austrian Population The aim of the study is to show a higher expression of the Y402H polymorphism in the complement factor H in patients with AMD compared to healthy individuals. --- Y402H ---

Y402H Comlement Factor H Polymorphism and Age-Related Macular Degeneration in the Austrian Population The aim of the study is to show a higher expression of the Y402H polymorphism in the complement factor H in patients with AMD compared to healthy individuals. --- Y402H --- --- Y402H ---

An interrelationship with the VEGF-plasma level shall give more hints into the pathomechanism of AMD. higher expression of the Y402H polymorphism in the complement factor H in patients with AMD compared to healthy individuals. --- Y402H ---

Primary Outcomes

Measure: higher expression of the Y402H polymorphism in the complement factor H in patients with AMD compared to healthy individuals

Secondary Outcomes

Measure: a correlation between a subsided infection with chlamydia and patients with AMD and a factor H polymorphism will be investigated. An interrelationship with the VEGF-plasma level shall give more hints into the pathomechanism of AMD

2 Does Complement Factor H Gene Polymorphism Play a Role in the Regulation of Vascular Tone in the Choroid?

Age related macular degeneration (AMD) is a multifactorial disease with a strong genetic component. Most importantly a genetic polymorphism in the gene encoding for the complement factor H (CFH) has been recently identified which is highly associated with an increased risk of developing AMD. This Tyr402His polymorphism located on chromosome 1q31 has been implicated to play a role in the development of the disease. Given that it is known that impaired regulation of choroidal vascular tone is present in patients with AMD, the current study seeks to investigate whether the Tyr402His polymorphism is associated with altered choroidal autoregulation in healthy subjects. For this purpose a total of 100 healthy volunteers will be included in order to test the hypothesis that an impaired regulation of choroidal blood flow is present in subjects with homozygous Tyr402His variant.

NCT00708929 Genetic Polymorphism Macular Degeneration Regional Blood Flow Ocular Physiology Procedure: Squatting
MeSH: Macular Degeneration

This Tyr402His polymorphism located on chromosome 1q31 has been implicated to play a role in the development of the disease. --- Tyr402His ---

Given that it is known that impaired regulation of choroidal vascular tone is present in patients with AMD, the current study seeks to investigate whether the Tyr402His polymorphism is associated with altered choroidal autoregulation in healthy subjects. --- Tyr402His ---

For this purpose a total of 100 healthy volunteers will be included in order to test the hypothesis that an impaired regulation of choroidal blood flow is present in subjects with homozygous Tyr402His variant. --- Tyr402His ---

Tyr402His genotyping. --- Tyr402His ---

Primary Outcomes

Measure: Choroidal blood flow during isometric exercise

Time: 10 minutes

Measure: Tyr402His genotyping

Time: screening

Secondary Outcomes

Measure: Mean arterial pressure

Time: 20 minutes

Measure: Intraocular pressure

Time: before and after blood flow measurements

Measure: Systolic/diastolic blood pressure

Time: 20 minutes

Measure: Pulse rate

Time: 20 minutes

3 Does VEGF or Complement Factor H Gene Polymorphism Play a Role in the Treatment Success With VEGF Inhibitors in Patients With CNV?

Age related macular degeneration (AMD) is a multifactorial disease with a strong genetic component. Most importantly a genetic polymorphism in the gene encoding for the complement factor H (CFH) has been recently identified which is highly associated with an increased risk of developing AMD. This Tyr402His polymorphism located on chromosome 1q31 has been implicated to play a role in the development of the disease. For this purpose a total of 200 patients with wet AMD will be included in the study. As described in detail below, the current study aims to identify potentially non-responders to anti-VEGF therapy based on genetic analysis of VEGF polymorphism and complement factor H polymorphism.

NCT00813514 Choroidal NeoVascularization Age-Related Macular Degeneration Genetic: VEGF genotyping
MeSH: Macular Degeneration Choroidal Neovascularization Neovascularization, Pathologic

This Tyr402His polymorphism located on chromosome 1q31 has been implicated to play a role in the development of the disease. --- Tyr402His ---

Primary Outcomes

Measure: Visual acuity using ETDRS charts

Time: 2 x 5 minutes

Measure: Central retinal thickness (Optical coherence tomography)

Time: 2 x 20 minutes

Measure: VEGF genotyping

Time: 1 week

4 An Open-label, Phase 2a Study to Evaluate Pazopanib Eye Drops Administered for 12 Weeks to Patients With Neovascular Age-related Macular Degeneration

The purpose of this 12 week, open-label study is to investigate the safety and efficacy of a single dose regimen of pazopanib eye drop for neovascular AMD.

NCT01362348 Macular Degeneration Drug: pazopanib eye drops
MeSH: Macular Degeneration

Blood samples were collected without restriction for the time interval between blood draw and the last dose of pazopanib eye drops.. Inclusion Criteria: Subjects eligible for enrolment in the study must meet all of the following criteria: - Consent: Subject understands the procedures, agrees to participate in the study (including participation in the CFH Y402H pharmacogenetic research), and has signed and dated the informed consent form prior to the initiation of any study-related activities. --- Y402H ---

desferoximine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, and ethambutol) - Use of systemic steroids (>10 mg prednisone or equivalent/day) within 14 days of the start of treatment - Use of prohibited medications within the restricted timeframe relative to the start of study medication (See Section 5.5.2) - Use of an investigational drug within 30 days of screening - History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation - A condition or situation, which, in the opinion of the investigator, may result in significant risk to the patient, confound the study results or interfere significantly with participation Inclusion Criteria: Subjects eligible for enrolment in the study must meet all of the following criteria: - Consent: Subject understands the procedures, agrees to participate in the study (including participation in the CFH Y402H pharmacogenetic research), and has signed and dated the informed consent form prior to the initiation of any study-related activities. --- Y402H ---

Primary Outcomes

Description: CRT was the distance between the inner limiting membrane of the retina and the inner border of the retinal pigment epithelium/choriocapillaris band, inclusive of sub retinal fluid, measured in the central 1 millimeter (mm) of the Cube scan. OCT assessments were performed using SPECTRALIS spectral domain OCT. Images were evaluated by investigator for safety monitoring, and by a central reading center for eligibility determination and pharmacodynamics (PD) effects. Observed case (OC) data set was used for analysis in this analysis dataset, a missing assessment at any scheduled time point was considered unevaluable, was not imputed and was not included in data analysis. Baseline was defined as the assessments performed between Day -3 to -1. Change from Baseline was calculated by subtracting the baseline value from the individual post-randomization value at Day 29.

Measure: Change From Baseline in Central Retinal Lesion Thickness (CRT) as Measured by Optical Coherence Tomography (OCT) at Day 29

Time: Baseline (Week 0) and Day 29

Description: BCVA was measured in the study eye using the EVA chart starting at a test distance of 4 meters. The BCVA score is the number of letters read correctly by the participant. A decrease in the BCVA score indicates a worsening of vision while higher scores indicates improvement of VA. Baseline was defined as the assessments performed between Day -3 to -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-randomization value at Day 29.

Measure: Change From Baseline in Best Correct Visual Acuity (BCVA) as Measured by the Number of Letters Determined by Electronic Early Treatment Diabetic Retinopathy [ETDRS] Study Visual Acuity (EVA) at Day 29

Time: Baseline (Day -3 to -1) and Day 29

Secondary Outcomes

Description: CRLT was the manual measurement of the distance between the inner limiting membrane of the retina and the inner border of the choriocapillaris, inclusive of subretinal or sub-retinal pigment epithelium fluid collections and of the thickness of any observable choroidal neovascular membrane or scar tissue, evaluated in the central 1 mm of the Cube scan. OCT assessments were performed using SPECTRALIS spectral domain OCT. Baseline was defined as the assessments performed between Day -3 to -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-randomization value at Day 29.

Measure: Change From Baseline in Central Retinal Lesion Thickness (CRLT) Over Time

Time: Baseline (Week -3 to -1) Up to Follow-up (Day 102)

Description: OCT was used for the determination of retinal morphology changes in the study eye which included assessments of SR fluid (an exudate between the retina and choroid from various sources including the vitreous cavity, subarachnoid space, or abnormal vessels) and PED (retinal pigment epithelium separates from the underlying Bruch's membrane due to the presence of blood, serous exudate, drusen, or a neovascular membrane). Baseline was defined as the assessments performed between Day -3 to -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-randomization value at Day 29.

Measure: Change From Baseline in Intraretinal (IR) or Subretinal (SR) Fluid Thickness, Intraretinal Cysts or Serous Retinal Pigment Epithelial Detachment (PED Thickness) Over Time

Time: Baseline (Week -3 to -1) Up to Follow-up (Day 102)

Description: BCVA was measured in the study eye using the EVA chart starting at a test distance of 4 meters. The BCVA score is the number of letters read correctly by the participant. A decrease in the BCVA score indicates a worsening of vision while higher scores indicates improvement of VA. Baseline was defined as the assessments performed between Day -3 to -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-randomization value at Day 29.

Measure: Change From Baseline in BCVA Over Time

Time: Baseline (Week -3 to -1) Up to Follow-up (Day 102)

Description: CNV was the measurement of the combined classic and occult neovascular lesion including areas of classic neovascularization, late staining of undetermined origin and fibrovascular PED. CNV total lesion complex size was the measurement of the entire lesion including classic and occult neovascular components as well as contagious blood and/or blocked fluorescence and/or serous PED. FA uses fundus photography (FP) to capture images of injected dye circulating throughout the retinal blood vessels to assess leaking, swelling/circulation problems caused by various eye diseases like diabetic retinopathy and wet macular degeneration. A fluorescein angiogram was obtained at Day 29. Images were evaluated by investigator for eligibility and by a central reading center for determination of PD effect. Baseline was defined as the assessments performed between Day -3 to -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-randomization value at Day 29.

Measure: Change From Baseline in the Area of Choroidal Neovascular (CNV) Size and CNV Total Lesion Complex Size as Measured by Fluorescein Angiography (FA) at Day 29

Time: Baseline (Day -3 to -1) and Day 29

Description: Fundus photography involves capturing of images of the center of the very back inner wall of the eye — the retina, optic nerve, macula and main retinal blood vessels. The parameters assessment were heme SR hemorrhage (absence or presence at the location), heme IR hemorrhage (absence or presence at the location), SR fluid (absence or presence at location), fibrosis (absence or presence at location), atrophy (absence or presence of atrophic changes) and pigment (absence or presence at location). A protocol set of fundus photographs were obtained at Day 29. Images were read by the investigator for eligibility determination, and by a central reading center for determination of PD effect. Data has been presented for number of participants with changes in eye characteristics in the study eye at Day 29.

Measure: Number of Participants With Change in Charactertsics (Atrophy, Pigment, SR Hemorrhage, IR Hemorrhage, SR Fluid and Fibrosis) as Measured by FP

Time: Day 29

Description: At any time during the study, including the follow-up period, rescue treatment (standard of care) was given based on the clinical judgment of the investigator. Rescue treatment was to be strongly considered for participants whose center subfield thickness had increased by >50 microns from the lowest value on study or whose BCVA decreased by more than 5 letters compared to baseline and who also had persistent fluid by OCT. Data has been reported for the number of participants with their percentages who required any rescue medication administration until follow-up.

Measure: Number of Participants Who Received Rescue Medication

Time: Up to follow-up (Day 102)

Description: An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury.

Measure: Number of Participants With Ocular Adverse Events (AEs), Non-ocular AEs, Serious Ocular AEs and Serious Non-ocular AEs

Time: Until Follow-up (Day 102)

Description: A complete eye examination was performed to include the following: Examination of eyelids and lashes (including meibomian glands), Pupil, motility and confrontation visual field examination, Slit lamp evaluation of anterior ocular structures (including conjunctiva, tear film, cornea with fluorescein staining, anterior chamber, iris, lens, and anterior vitreous), Intraocular pressure (IOP) measurement and Dilated Fundus Examination (Indirect ophthalmoscopy and slit lamp biomicroscopy). Data has been presented in a consolidated format for the total number of participants with values of potential clinical concern for complete ophthalmic examinations until Day 102.

Measure: Number of Participants With Values of Potential Clinical Concern for Ocular Assessments on General Ophthalmic Examination

Time: Up to Follow-up (Day 102)

Description: Vital sign assessments included systolic blood pressure, diastolic blood pressure and heart rate. The potential clinical concern range for systolic blood pressure was <85 and >160 millimeters of mercury, diastolic blood pressure <45 and > 100 millimeters of mercury, heart rate <40 and >110 beats per minute. Data has been presented in a consolidated format for the total number of participants with values of potential clinical concern for systolic blood pressure, diastolic blood pressure and heart rate until Day 102.

Measure: Number of Participants With Vital Sign Data of Potential Clinical Concern

Time: Up to Follow-up (Day 102)

Description: Clinical chemistry parameters included albumin, alkaline phosphatase, alanine amino transferase, aspartate amino transferase, direct bilirubin, total bilirubin, calcium, chloride, carbon dioxide, creatinine, thyroxine (T3 free), gamma glutamyl transferase, glucose, potassium, sodium, total protein, total T3, urea, uric acid while hematology included basophils, eosinophils, hemoglobin, hematocrit, lymphocytes, mean corpuscle hemoglobin concentration, mean corpuscle hemoglobin, mean corpuscle volume, monocytes, segmented neutrophils, total neutrophils, platelet count, red blood cell count, reticulocytes and white blood cell count. The potential clinical concern ranges were as follows: glucose-low <3 and high >9 millimoles per liter (mmol/L), carbon dioxide-low <18 and high >34 mmol/L, lymphocyte-low <0.8 giga per liter (G/L) and platelet count was <100 and high >550 G/L. Data has been presented for the number of participants with values high and low of potential clinical concern.

Measure: Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern

Time: Up to Follow-up (Day 102)

Description: Urinalysis measurements included assessments for red blood cells and white blood cells via microscopic examination while assessments for urine protein by standard dipstick analysis. Data has been presented for the number of participants with abnormal urinalysis results.

Measure: Number of Participants With Abnormal Urinalysis Data by Urine Microscopy and Dipstick Analysis

Time: Up to Follow-up (Day 102)

Description: Throughout the study, 1 to 4 blood samples (2 mL) were collected from each participants for the analysis of plasma pazopanib concentrations between 0.55 to 10.83 hours post-dose on Weeks 2, 3, 4, 6 (unplanned), 8 (unplanned) and 12. The concentrations from the three blood samples per participant were averaged and then the values were averaged through all the participants. Blood samples were collected without restriction for the time interval between blood draw and the last dose of pazopanib eye drops.

Measure: Summary of Plasma Pazonib Concentration

Time: Up to Week 12


HPO Nodes