Ignite Creation Date:
2024-05-06 @ 4:51 PM
Last Modification Date:
2024-10-26 @ 2:17 PM
Study NCT ID:
NCT05116501
Status:
UNKNOWN
Last Update Posted:
2022-03-04
First Post:
2021-09-27
Brief Title:
Genetic Background of Patients With Low Von Willebrand Factor Levels
Sponsor:
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Organization:
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Study Overview
Official Title:
Novel Insights Into the Genetic Background of Patients With Low Von Willebrand Factor Levels Using Next-generation Sequencing
Status:
UNKNOWN
Status Verified Date:
2021-09
Last Known Status:
RECRUITING
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:
LOVMIC
Brief Summary:
Von Willebrand disease VWD is caused by either quantitative or qualitative von Willebrand VWF defects and is the commonest inherited bleeding disorder with an estimated prevalence of about 1 in the general population According to several guidelines patients with a mild quantitative reduction in VWF 30-50 IUdL should be labeled as low VWF Quantitatively VWF defects account for almost 75 of all cases with VWD and among them low VWF seems to be the most common form Studies on patients with VWD reported only around 50 VWF mutations in low VWF cases indicating that some possible genes outside of the VWF gene may be responsible for the low VWF levels To date using genome-wide association study GWAS more than 19 non-VWF loci such as ABO blood group system Stabilin 2 Scavenger Receptor Class A Member 5 C-Type Lectin Domain Family 4 Member M etc were identified to be associated with VWF levels The identified genes are related to different mechanisms of the VWF life-cycle such as synthesis secretion glycosylation or clearance Despite the importance of the genetic background of low VWF levels for understanding its etiology this issue is not well investigated yet Thus the Low VWF Milan Cohort LOVMIC Study is designed to address some unanswered questions in patients with low VWF
Detailed Description:
Despite the absence of mutation in the VWF gene in a significant number of individuals with reduced VWF levels and also the lack of knowledge for the responsible mechanisms this study sought to determine the following goals
Evaluation of the genetic background of low VWF level dilemma and identifying the gene s outside of the VWF gene that is associated with decreased VWF levels
Evaluating the correlation between candidate variants and patients bleeding manifestations
Study design
Non-pharmacological Interventional National Monocentric Study Promoter Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico Coordinating center and patient recruitment unit Department of General Medicine - Hemostasis and Thrombosis - Angelo Bianchi Bonomi Hemophilia and Thrombosis Center
Setting outpatients clinic
The study population will be selected from the referral adult patientshealthy controls to the A Bianchi Bonomi Hemophilia and Thrombosis Center in Fondazione IRCCS Ca Granda Maggiore Policlinic hospital
Recruiting method
Selected patients base on the previous laboratory results will be invited to participate in the study by physicians at the center through phone calls Also normal controls age- and sex-matched with patients will be enrolled in the study Data regarding the healthy controls will be obtained either from the available public database or obtained by evaluation of collected samples from the normal subjects who have been selected by the A Bianchi Bonomi Hemophilia and Thrombosis Center
Enrolment visit and blood samples collection
Following the agreement of patients for participating in the study and signing the informed consent 3 tubes each 35 ml of the blood sample will be collected for performing VWD-related laboratory tests VWF antigen VWFAg VWF ristocetin cofactor VWFRCo Factor VIII clotting assay FVIIIC and Whole-exome sequencing WES In addition a routinely clinical examination will be done by specialized physicians according to a Case Report Form CRF to collect the data regarding age sex blood group and clinical manifestations including the International Society on Thrombosis and Haemostasis Bleeding Assessment Tool ISTH-BAT
Genetic analysis
Genomic DNA will be extracted using the automated instrument from QIAGEN available in the central genetic laboratory at the Fondazione IRCCS Ca Granda Maggiore Policlinic hospital
WES will be performed on all samples using NextSeq 2000 instrument in the central genetic laboratory at the Fondazione IRCCS Ca Granda Maggiore Policlinic hospital
Data will be analyzed following the same strategy in both cases and controls First the VWF gene will be evaluated Then the analysis will be extended to the other genes that were previously described as related to VWF level variations Lastly exome data will be considered
The association between VWF levels and candidate variants will be assessed
All analyses will be performed considering variants minor allele frequency MAF age sex ABO to control for confounding
Evaluation of the genetic background of low VWF level dilemma and identifying the gene s outside of the VWF gene that is associated with decreased VWF levels
Evaluating the correlation between candidate variants and patients bleeding manifestations
Study design
Non-pharmacological Interventional National Monocentric Study Promoter Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico Coordinating center and patient recruitment unit Department of General Medicine - Hemostasis and Thrombosis - Angelo Bianchi Bonomi Hemophilia and Thrombosis Center
Setting outpatients clinic
The study population will be selected from the referral adult patientshealthy controls to the A Bianchi Bonomi Hemophilia and Thrombosis Center in Fondazione IRCCS Ca Granda Maggiore Policlinic hospital
Recruiting method
Selected patients base on the previous laboratory results will be invited to participate in the study by physicians at the center through phone calls Also normal controls age- and sex-matched with patients will be enrolled in the study Data regarding the healthy controls will be obtained either from the available public database or obtained by evaluation of collected samples from the normal subjects who have been selected by the A Bianchi Bonomi Hemophilia and Thrombosis Center
Enrolment visit and blood samples collection
Following the agreement of patients for participating in the study and signing the informed consent 3 tubes each 35 ml of the blood sample will be collected for performing VWD-related laboratory tests VWF antigen VWFAg VWF ristocetin cofactor VWFRCo Factor VIII clotting assay FVIIIC and Whole-exome sequencing WES In addition a routinely clinical examination will be done by specialized physicians according to a Case Report Form CRF to collect the data regarding age sex blood group and clinical manifestations including the International Society on Thrombosis and Haemostasis Bleeding Assessment Tool ISTH-BAT
Genetic analysis
Genomic DNA will be extracted using the automated instrument from QIAGEN available in the central genetic laboratory at the Fondazione IRCCS Ca Granda Maggiore Policlinic hospital
WES will be performed on all samples using NextSeq 2000 instrument in the central genetic laboratory at the Fondazione IRCCS Ca Granda Maggiore Policlinic hospital
Data will be analyzed following the same strategy in both cases and controls First the VWF gene will be evaluated Then the analysis will be extended to the other genes that were previously described as related to VWF level variations Lastly exome data will be considered
The association between VWF levels and candidate variants will be assessed
All analyses will be performed considering variants minor allele frequency MAF age sex ABO to control for confounding
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None