Ignite Creation Date:
2024-05-06 @ 8:23 PM
Last Modification Date:
2024-10-26 @ 3:26 PM
Study NCT ID:
NCT06360913
Status:
RECRUITING
Last Update Posted:
2024-04-12
First Post:
2024-01-31
Brief Title:
Blood Spot and Urine Metabolomic Screening Applied to Rare Diseases
Sponsor:
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Organization:
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Study Overview
Official Title:
Blood Spot and Urine Metabolomic Screening Applied to Rare Diseases
Status:
RECRUITING
Status Verified Date:
2024-04
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:
BUSARD
Brief Summary:
The primary goal of this study is to establish a biobank of dried blood spots and urines from a large control cohort and collect several cohorts as large as possible of patients affected or suspected of being affected by rare diseases mainly hereditary metabolic diseases or by autism spectrum disorders
A metabolomic database using a high-resolution mass spectrometer ie the Device will be generated and specific biomarkers for the diseases will be confirmed or uncovered The ultimate goal is to facilitate and improve the diagnosis and screening of the patients affected by these disorders but also to improve the knowledge about the biochemical mechanisms involved over the course of the selected pathologies
High-resolution mass spectrometry allows the measurement of thousands of metabolites in a single analysis The current biochemical tests used for the diagnosis of hereditary metabolic diseases are only using a combination of maximum a few dozens of biomarkers in one analysis
Objectives Unravel new biomarkers for diagnosis - explore the altered pathways Uncover andor validate newborn screening biomarkers through retrospective analysis of preserved newborn DBS from confirmed patients useful for first or second tier biochemical NBS testing Validation of LC-MS qTOF for metabolomics screening as first line diagnostic test thousands of metabolites using diagnostic algorithms modified z-scores continuous optimization by adding new cases and new controls in the database Generation of a biobank of urines and DBS from rare diseases IEMs from a large reference population useful for other research applications
A metabolomic database using a high-resolution mass spectrometer ie the Device will be generated and specific biomarkers for the diseases will be confirmed or uncovered The ultimate goal is to facilitate and improve the diagnosis and screening of the patients affected by these disorders but also to improve the knowledge about the biochemical mechanisms involved over the course of the selected pathologies
High-resolution mass spectrometry allows the measurement of thousands of metabolites in a single analysis The current biochemical tests used for the diagnosis of hereditary metabolic diseases are only using a combination of maximum a few dozens of biomarkers in one analysis
Objectives Unravel new biomarkers for diagnosis - explore the altered pathways Uncover andor validate newborn screening biomarkers through retrospective analysis of preserved newborn DBS from confirmed patients useful for first or second tier biochemical NBS testing Validation of LC-MS qTOF for metabolomics screening as first line diagnostic test thousands of metabolites using diagnostic algorithms modified z-scores continuous optimization by adding new cases and new controls in the database Generation of a biobank of urines and DBS from rare diseases IEMs from a large reference population useful for other research applications
Detailed Description:
DESIGN OF THE CLINICAL INVESTIGATION
Interventional multicenter study using high-resolution mass spectrometry applied to dried blood spots and urine samples generating metabolomic data
The study will start by the establishment of a biobank according to group description
The samples dried blood spots DBS and urine samples for each subject will be collected in respective co-investigator centers before being shipped to the central biobank of Cliniques universitaires Saint Luc CUSL DBS are allowed to be kept at room temperature dry and protected from light if shipped to CUSL within 2 weeks upon sampling
The sampling procedure occurring at each co-investigating center will include in the following order
Information about the study explanations by the investigator or hisher delegate
Collection of informed consent forms to participate including agreement of multiple sampling at another time point for groups II and III only
A confidential medical questionnaireCRF will be collected reduced form for subjects in the Group 1-control
DBS and urine sampling Subjects for which only neonatal DBS is available will be accepted as well
The identity and participation of the subjects in the experimentation will remain strictly confidential in accordance with the European General Data Protection Regulation of April 27 2016 in application since May 25 2018 the Belgian law of July 30 2018 on the protection of privacy with regard to the processing of personal data as well as the law of August 22 2002 on the rights of patients Personal data will be coded Subjects will not be identified by name or in any other recognisable way in any of the records results or publications related to the experimentation
The investigators of the study will identify the potential subjects that seem to meet the eligibility criteria
The medical doctor or delegate will explain the study Then if the subject andor the parents agree the informed consent will be signed before any sampling
Multiple sampling at different time points will be allowed for a single informed consent form ICF
The co-investigator centers will temporarily keep pseudonymized samples and will send periodically the accumulated samples frozen to the CUSL laboratory for biobanking The samples will be stored at -80C in CUSL biobank before and after analysis The time of reception and transfer at -80C at CUSL will be Recorded in REDCAP
Later generation of datasets representative of the metabolome in DBS and urine samples by liquid chromatography coupled to high resolution mass spectrometry LC-MS-q-TOF analysis will be performed
The metabolomics analysis by LC-MS-q-TOF will use a SYNAPT-XS instrument from Waters Several columns will be used in negative and positive electrospray acquisition modes allowing the generation of complementary metabolomic datasets containing several thousands of features ranged by exact mass mz including spectra after energy collision and retention time measurements Quality controls and pooled samples will be analyzed at each batch of run during the metabolomics study
After data analysis using progenesis QI Unifi and R-package for metabolomics analysis the results will be discussed and shared with the co-investigators and the expected results will hopefully be published in a peer-reviewed journal If necessary ie to confirm genetically an unusual metabolomic profile or a secondary finding and if the consent is obtained from the patient complementary biochemical testing on initial DBS andor urine samples and genetic testing from the DBS will be performed upon discussion and agreement with the co-investigators of the study If required ie if a new diagnosis is suspected biochemically andor genetically subjects will be contacted after agreement of the co-investigators of the study
The samples needed for this study will be divided into 3 main groups each subdivided according to age categories the first group is the main healthy group Group 1 allowing to generate a reference metabolomic database The two other groups correspond to groups of patients with pathologies whose diagnosis is either confirmed Group 2 or suspected Group 3
Total expected 3366 subjects
30 for technical optimization additionally to DBS and urine whole blood tubes will be sampled
1080 residual human body material RHBM from newborn screening centres group 1
1056 controls group 1
1200 patients groups 2 and 3
The minimum number of samples necessary to generate a reference interval using a non-parametric method is 120 samples according to CLSI28-A3C guidelines Therefore the investigators set a target of minimum 120 samples collected per category of age Samples will be equitably distributed by sex season and participating centers thus geographical origin For the newborn categories since the easier availability of large number of control samples using anonymized residual samples from newborn screening centers the target number of control samples will be larger On the other hand urines samples wont be collected for subjects for newborn categories
Group 2 includes individuals with a known pathology whose diagnosis is confirmed by a genetic test genetic variants considered as pathogenic or likely pathogenic according to American College of Human Genetics classification or a biochemical reference test associated to a typical clinical feature For autism spectrum disorders recruited patients should be included according to the Diagnostic and Statistical Manual DSM V classification Subgroups are defined according to the pathology affecting each individual classification according to the affected gene mode of inheritance and type of mutation the primarily target pathologies considered are genetic metabolic diseases but other rare diseases and autism spectrum disorders are also targeted
Group 3 includes individuals for whom an rare disease is suspected based on the clinical data but not confirmed including patients for whom the genetic and biochemical tests are still in progress or inconclusive If the status of an individual changes before the end of the study after the confirmation of a diagnosis communicated anonymously by the recruiting co-investigator due to results obtained independently outside the study or due to the results of the study specific biomarkers andor scoring andor genetic confirmation using second tier testing the subject will then be transferred to its corresponding group 2 These patients will be recruited in all the participating centers
Interventional multicenter study using high-resolution mass spectrometry applied to dried blood spots and urine samples generating metabolomic data
The study will start by the establishment of a biobank according to group description
The samples dried blood spots DBS and urine samples for each subject will be collected in respective co-investigator centers before being shipped to the central biobank of Cliniques universitaires Saint Luc CUSL DBS are allowed to be kept at room temperature dry and protected from light if shipped to CUSL within 2 weeks upon sampling
The sampling procedure occurring at each co-investigating center will include in the following order
Information about the study explanations by the investigator or hisher delegate
Collection of informed consent forms to participate including agreement of multiple sampling at another time point for groups II and III only
A confidential medical questionnaireCRF will be collected reduced form for subjects in the Group 1-control
DBS and urine sampling Subjects for which only neonatal DBS is available will be accepted as well
The identity and participation of the subjects in the experimentation will remain strictly confidential in accordance with the European General Data Protection Regulation of April 27 2016 in application since May 25 2018 the Belgian law of July 30 2018 on the protection of privacy with regard to the processing of personal data as well as the law of August 22 2002 on the rights of patients Personal data will be coded Subjects will not be identified by name or in any other recognisable way in any of the records results or publications related to the experimentation
The investigators of the study will identify the potential subjects that seem to meet the eligibility criteria
The medical doctor or delegate will explain the study Then if the subject andor the parents agree the informed consent will be signed before any sampling
Multiple sampling at different time points will be allowed for a single informed consent form ICF
The co-investigator centers will temporarily keep pseudonymized samples and will send periodically the accumulated samples frozen to the CUSL laboratory for biobanking The samples will be stored at -80C in CUSL biobank before and after analysis The time of reception and transfer at -80C at CUSL will be Recorded in REDCAP
Later generation of datasets representative of the metabolome in DBS and urine samples by liquid chromatography coupled to high resolution mass spectrometry LC-MS-q-TOF analysis will be performed
The metabolomics analysis by LC-MS-q-TOF will use a SYNAPT-XS instrument from Waters Several columns will be used in negative and positive electrospray acquisition modes allowing the generation of complementary metabolomic datasets containing several thousands of features ranged by exact mass mz including spectra after energy collision and retention time measurements Quality controls and pooled samples will be analyzed at each batch of run during the metabolomics study
After data analysis using progenesis QI Unifi and R-package for metabolomics analysis the results will be discussed and shared with the co-investigators and the expected results will hopefully be published in a peer-reviewed journal If necessary ie to confirm genetically an unusual metabolomic profile or a secondary finding and if the consent is obtained from the patient complementary biochemical testing on initial DBS andor urine samples and genetic testing from the DBS will be performed upon discussion and agreement with the co-investigators of the study If required ie if a new diagnosis is suspected biochemically andor genetically subjects will be contacted after agreement of the co-investigators of the study
The samples needed for this study will be divided into 3 main groups each subdivided according to age categories the first group is the main healthy group Group 1 allowing to generate a reference metabolomic database The two other groups correspond to groups of patients with pathologies whose diagnosis is either confirmed Group 2 or suspected Group 3
Total expected 3366 subjects
30 for technical optimization additionally to DBS and urine whole blood tubes will be sampled
1080 residual human body material RHBM from newborn screening centres group 1
1056 controls group 1
1200 patients groups 2 and 3
The minimum number of samples necessary to generate a reference interval using a non-parametric method is 120 samples according to CLSI28-A3C guidelines Therefore the investigators set a target of minimum 120 samples collected per category of age Samples will be equitably distributed by sex season and participating centers thus geographical origin For the newborn categories since the easier availability of large number of control samples using anonymized residual samples from newborn screening centers the target number of control samples will be larger On the other hand urines samples wont be collected for subjects for newborn categories
Group 2 includes individuals with a known pathology whose diagnosis is confirmed by a genetic test genetic variants considered as pathogenic or likely pathogenic according to American College of Human Genetics classification or a biochemical reference test associated to a typical clinical feature For autism spectrum disorders recruited patients should be included according to the Diagnostic and Statistical Manual DSM V classification Subgroups are defined according to the pathology affecting each individual classification according to the affected gene mode of inheritance and type of mutation the primarily target pathologies considered are genetic metabolic diseases but other rare diseases and autism spectrum disorders are also targeted
Group 3 includes individuals for whom an rare disease is suspected based on the clinical data but not confirmed including patients for whom the genetic and biochemical tests are still in progress or inconclusive If the status of an individual changes before the end of the study after the confirmation of a diagnosis communicated anonymously by the recruiting co-investigator due to results obtained independently outside the study or due to the results of the study specific biomarkers andor scoring andor genetic confirmation using second tier testing the subject will then be transferred to its corresponding group 2 These patients will be recruited in all the participating centers
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