Ignite Creation Date:
2024-05-06 @ 3:29 PM
Last Modification Date:
2024-10-26 @ 1:51 PM
Study NCT ID:
NCT04654442
Status:
COMPLETED
Last Update Posted:
2021-09-29
First Post:
2020-12-03
Brief Title:
Feasibility and Analytic Performance of TestNPass IVDMD for CoViD-19 Diagnosis on Saliva Sample
Sponsor:
University Hospital Grenoble
Organization:
University Hospital Grenoble
Study Overview
Official Title:
Evaluation of the Feasibility and Analytic Performance of TestNPass In Vitro Diagnosis Medical Device for CoViD-19 Diagnosis on Saliva Sample a Pilot Study
Status:
COMPLETED
Status Verified Date:
2021-09
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:
GraphealNpas
Brief Summary:
COVID19 pandemic and SARS-CoV-2 rapid progression worldwide are already historical landmarks of the 21st century owing to the magnitude of the event and the collective response that populations have adopted to face such threat This menace has imposed an unprecedented reactivity to promptly deliver answers in various fields and specifically in termes of diagnostic capabilities
The very first tests to be used were based on PCR reactions and on deep nasopharyngeal sampling But this has shown to be insufficient to prevent contaminations and limit the progression of the disease This approach requires important infrastructure thus limiting the extent to which it can be delivered Moreover nasopharyngeal swab is highly intrusive and therefore is not suitable for repeated testing of asymptomatic patients in surveillance programs
Actual need is based on new tests offering new capabilities both in terms of wide range availability ease of use and reduced time-to-result duration Such tests affordable and that can be performed outside the lab would ultimately relief pressure on healthcare workers and laboratory facilities as well as help test massively wide range of populations thus limiting viral dissemination
Such innovating test device has been developped by the start-up Grapheal and the present study will ultimately demonstrate the feasibility of COVID-19 diagnostic using this test
The very first tests to be used were based on PCR reactions and on deep nasopharyngeal sampling But this has shown to be insufficient to prevent contaminations and limit the progression of the disease This approach requires important infrastructure thus limiting the extent to which it can be delivered Moreover nasopharyngeal swab is highly intrusive and therefore is not suitable for repeated testing of asymptomatic patients in surveillance programs
Actual need is based on new tests offering new capabilities both in terms of wide range availability ease of use and reduced time-to-result duration Such tests affordable and that can be performed outside the lab would ultimately relief pressure on healthcare workers and laboratory facilities as well as help test massively wide range of populations thus limiting viral dissemination
Such innovating test device has been developped by the start-up Grapheal and the present study will ultimately demonstrate the feasibility of COVID-19 diagnostic using this test
Detailed Description:
ACTUAL KNOWLEDGE ABOUT DIAGNOSTIC STRATEGIES Actual strategy for rapid and accurate diagnostic relies heavily almost solely on RT-PCR based tests The French Scientific Board advising the national government in the management of this epidemic has brought back on September 3rd the three-axis policy Test - Track - Isolate as the central response to the COVID-19 progression This strategy is also the response promoted by WHO since March If properly applied this approach allows high-performance in identifying positive cases and spotting transmission chains thus allowing to specifically isolate and quarantine infectious patients The expected outcome is a halting epidemic allowing economic recovery and protection of populations
Rise in French laboratory capacities regarding their ability to perform the required tests has been achieved since the early days of COVID-19 Since August 10th we have reached the pace of 100000 daily tests nationwide and peaked above 300000 tests per day as of October 26th Santé Publique France
However the need to lockdown the entire French population for a second time is the demonstration of the limits of this strategy Issues can be summarized in a few key points
The hassle of performing as many tests as needed over the whole national territory has proven difficult and does not allow control of local epidemic bursts
Repetitive sampling for asymptomatic patients to confirm viral clearance and lack of viral shedding raises strong questions regarding its feasibility
The need for high quality sampling for RT-PCR tests accurately reaching nasopharyngeal cavity requires trained staff whose availability is limited Swab collection remains an important bottleneck nationwide
Important consumption of PPE personal protective equipment for sampling staff adds an unnecessary tension in supply chains In the light of these issues there is an urgent need to transition from RT-PCR tests to novel diagnostic techniques capable of addressing the above-mentioned key problems Rapid Antigenic Tests are being evaluated and used already in some facilities and in very controlled settings However these tests do have important limitations and their relatively low sensibility in real-life setting around 60 of positive agreement with RT-PCR for best-performing tests is an issue that need to be quickly addressed to avoid jeopardizing efforts made to widespread tests and keep public confidence Moreover Rapid Antigenic Tests deliver results in 15 to 30 minutes time much faster than traditional RT-PCR but still inadequate for massive population test in crowded places and public gathering airports shows and sporting events
ABOUT MEDICAL DEVICE INVOLVED
Vincent BOUCHIAT is a team leader former research senior and principal investigator from French science agency CNRS in the field of material science and physics and he established in 2019 a start-up Grapheal in Grenoble to upcycle his fundamental work on the unique properties of graphene allowing the synthesis of electronic polymers with bio-compatibility and biological detection capacities This work is patent-protected in cooperation with local university UGA which grants sustainability in the development of such technology
Since March 2020 Grapheal has been working on a single-use specific biosensor called TestNPass digital Covid Ag test strip thus allowing the rapid detection of SARS-CoV-2 This biosensor uses the electronic detection of the biochemical matching between specific antibodies directed against the virus The docking of the virus by stabilized antibodies leads to a change in conductance within the sensor electronic circuit similar to Seo and colleagues work This variation in electric conductance is measured by an ultraportable and autonomous circuit that can be paired with either a computer or a smartphone in order to be further analyzed
Proof of concept of the device has been realized by in vitro experiments putting together commercial samples containing recombinant structural proteins of the SARS-CoV-2 virus with the detection electrodes of the disposable antigenic test strip after dilution in a saline solution PBS Tested samples with Nucleocapsid and Spike proteins were able to trigger a change in conductance thus allowing detection of the viral surrogate Protein concentrations have been adjusted to match in vivo concentrations and an important work has been performed to ensure signal processing is robust reliable and repeatability of the measure
Encryption of the result within the on-board processing circuits of the device allow the development of a device fully compliant with personal data protection and grating GDPR compliance from the start
FEASIBILITY AND PAST EXPERIENCE OF INVOLVED TEAMS
The team from Grapheal is hosted within the BioPolis incubator facility which presence close to Grenoble Teaching Hospital CHUGA allows for narrow collaborations This start-up highlight the performances of bio sensing technologies based on graphene polymers Grapheal team has 7 members all of them holding PhDs in biological sciences or physics The team is led by Vincent BOUCHIAT who is a former principal investigator from French national agency for scientific research CNRS The team has been granted with prizes and rewards among which the i-lab 2020 contest held by the French Ministry of Scientific Research and Higher Education for innovating technologies
For this project the team has joined its forces with specialists of IVD and medical devices as well as knowledgeable support from regulation specialists Ultimately the team has been requesting the help from the virology team from Grenoble University Hospital CHUGA in order to set up the present proof-of-concept study the first of its kind to be performed in human samples
The virology team from Grenoble University hospital CHUGA is a pioneer in the development of molecular based assays for viral diagnostic Some of the now classical PCR and RT-PCR widely used for routine diagnostic in France have been set up within our team and laboratory These techniques and PCR kits now branded by BioMérieux company have been developed by collaborators from our lab thus granting us with a wide experience in diagnostic technique and molecular based technologies
The diagnostic of SARS-CoV-2 infection is performed within our laboratory since the early days of the pandemic We have been dealing with the very first infected patients from France as early as February 8th 2020 The diagnostic of these patients has greatly improved since then and SAR-CoV-2 detection is now performed as a regular daily test at an unprecedented rate Along with the development of cutting edge techniques including pseudo-virus neutralization assays our team now holds a highly skilled expertise regarding to COVID-19 questions
Both microbiological and clinical teams from CHUGA have been producing research projects and data about COVID-19 pandemic More than 10 clinical studies have been set-up and half of these protocols now enroll patients on a daily basis One of those has closed after inclusion of more than 200 subjects Moreover cooperation has been developed to reach more than 50 shared research projects with collaborators in France Among those the nation-wide projects DISCoVery and French-COVID have been main protocols where we matched expected targets
Altogether these past experiences are key for future success in the present study
RESEARCH HYPOTHESIS
The present study has a main target of demonstrating the feasibility of the Grapheal TestNPass device to accurately distinguish SARS-CoV-2 infections in a tested population If conclusive the evaluated test could help detect and therefore limit the spread of the virus upon national territory
The root hypothesis is as following the bond between the antibody directed against viral proteins and the virus itself is enough to generate within a graphene base semi-conductor a change in conductance that is measurable and repeatable This electric current can therefore be used as a surrogate of viral infection viral shedding and viral infectiousness Obtained result being an electric impulse it will be easily transferred to a device for digital display
Simultaneously the present study will bring to light some of the following elements
Crucial information about ergonomic of the device for future development and improving This study being the first use outside of Grapheals team the feedbacks from users will be of great help to support future development of the device
Preliminary data on analytical performances Will the main goal of the present study is to demonstrate the feasibility of COVID-19 diagnosis with the device key performance date such as sensitivity specificity positive agreement and negative agreement will be estimated This will serve as a strong basis for both future studies and approval from regulatory agencies
Rise in French laboratory capacities regarding their ability to perform the required tests has been achieved since the early days of COVID-19 Since August 10th we have reached the pace of 100000 daily tests nationwide and peaked above 300000 tests per day as of October 26th Santé Publique France
However the need to lockdown the entire French population for a second time is the demonstration of the limits of this strategy Issues can be summarized in a few key points
The hassle of performing as many tests as needed over the whole national territory has proven difficult and does not allow control of local epidemic bursts
Repetitive sampling for asymptomatic patients to confirm viral clearance and lack of viral shedding raises strong questions regarding its feasibility
The need for high quality sampling for RT-PCR tests accurately reaching nasopharyngeal cavity requires trained staff whose availability is limited Swab collection remains an important bottleneck nationwide
Important consumption of PPE personal protective equipment for sampling staff adds an unnecessary tension in supply chains In the light of these issues there is an urgent need to transition from RT-PCR tests to novel diagnostic techniques capable of addressing the above-mentioned key problems Rapid Antigenic Tests are being evaluated and used already in some facilities and in very controlled settings However these tests do have important limitations and their relatively low sensibility in real-life setting around 60 of positive agreement with RT-PCR for best-performing tests is an issue that need to be quickly addressed to avoid jeopardizing efforts made to widespread tests and keep public confidence Moreover Rapid Antigenic Tests deliver results in 15 to 30 minutes time much faster than traditional RT-PCR but still inadequate for massive population test in crowded places and public gathering airports shows and sporting events
ABOUT MEDICAL DEVICE INVOLVED
Vincent BOUCHIAT is a team leader former research senior and principal investigator from French science agency CNRS in the field of material science and physics and he established in 2019 a start-up Grapheal in Grenoble to upcycle his fundamental work on the unique properties of graphene allowing the synthesis of electronic polymers with bio-compatibility and biological detection capacities This work is patent-protected in cooperation with local university UGA which grants sustainability in the development of such technology
Since March 2020 Grapheal has been working on a single-use specific biosensor called TestNPass digital Covid Ag test strip thus allowing the rapid detection of SARS-CoV-2 This biosensor uses the electronic detection of the biochemical matching between specific antibodies directed against the virus The docking of the virus by stabilized antibodies leads to a change in conductance within the sensor electronic circuit similar to Seo and colleagues work This variation in electric conductance is measured by an ultraportable and autonomous circuit that can be paired with either a computer or a smartphone in order to be further analyzed
Proof of concept of the device has been realized by in vitro experiments putting together commercial samples containing recombinant structural proteins of the SARS-CoV-2 virus with the detection electrodes of the disposable antigenic test strip after dilution in a saline solution PBS Tested samples with Nucleocapsid and Spike proteins were able to trigger a change in conductance thus allowing detection of the viral surrogate Protein concentrations have been adjusted to match in vivo concentrations and an important work has been performed to ensure signal processing is robust reliable and repeatability of the measure
Encryption of the result within the on-board processing circuits of the device allow the development of a device fully compliant with personal data protection and grating GDPR compliance from the start
FEASIBILITY AND PAST EXPERIENCE OF INVOLVED TEAMS
The team from Grapheal is hosted within the BioPolis incubator facility which presence close to Grenoble Teaching Hospital CHUGA allows for narrow collaborations This start-up highlight the performances of bio sensing technologies based on graphene polymers Grapheal team has 7 members all of them holding PhDs in biological sciences or physics The team is led by Vincent BOUCHIAT who is a former principal investigator from French national agency for scientific research CNRS The team has been granted with prizes and rewards among which the i-lab 2020 contest held by the French Ministry of Scientific Research and Higher Education for innovating technologies
For this project the team has joined its forces with specialists of IVD and medical devices as well as knowledgeable support from regulation specialists Ultimately the team has been requesting the help from the virology team from Grenoble University Hospital CHUGA in order to set up the present proof-of-concept study the first of its kind to be performed in human samples
The virology team from Grenoble University hospital CHUGA is a pioneer in the development of molecular based assays for viral diagnostic Some of the now classical PCR and RT-PCR widely used for routine diagnostic in France have been set up within our team and laboratory These techniques and PCR kits now branded by BioMérieux company have been developed by collaborators from our lab thus granting us with a wide experience in diagnostic technique and molecular based technologies
The diagnostic of SARS-CoV-2 infection is performed within our laboratory since the early days of the pandemic We have been dealing with the very first infected patients from France as early as February 8th 2020 The diagnostic of these patients has greatly improved since then and SAR-CoV-2 detection is now performed as a regular daily test at an unprecedented rate Along with the development of cutting edge techniques including pseudo-virus neutralization assays our team now holds a highly skilled expertise regarding to COVID-19 questions
Both microbiological and clinical teams from CHUGA have been producing research projects and data about COVID-19 pandemic More than 10 clinical studies have been set-up and half of these protocols now enroll patients on a daily basis One of those has closed after inclusion of more than 200 subjects Moreover cooperation has been developed to reach more than 50 shared research projects with collaborators in France Among those the nation-wide projects DISCoVery and French-COVID have been main protocols where we matched expected targets
Altogether these past experiences are key for future success in the present study
RESEARCH HYPOTHESIS
The present study has a main target of demonstrating the feasibility of the Grapheal TestNPass device to accurately distinguish SARS-CoV-2 infections in a tested population If conclusive the evaluated test could help detect and therefore limit the spread of the virus upon national territory
The root hypothesis is as following the bond between the antibody directed against viral proteins and the virus itself is enough to generate within a graphene base semi-conductor a change in conductance that is measurable and repeatable This electric current can therefore be used as a surrogate of viral infection viral shedding and viral infectiousness Obtained result being an electric impulse it will be easily transferred to a device for digital display
Simultaneously the present study will bring to light some of the following elements
Crucial information about ergonomic of the device for future development and improving This study being the first use outside of Grapheals team the feedbacks from users will be of great help to support future development of the device
Preliminary data on analytical performances Will the main goal of the present study is to demonstrate the feasibility of COVID-19 diagnosis with the device key performance date such as sensitivity specificity positive agreement and negative agreement will be estimated This will serve as a strong basis for both future studies and approval from regulatory agencies
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2020-A03087-32 | OTHER | ID RCB | None |