Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02896634 |
| Other study ID # |
9622 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
October 1, 2015 |
| Est. completion date |
September 1, 2018 |
Study information
| Verified date |
August 2019 |
| Source |
University Hospital, Montpellier |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Dried Blood Spot or DBS is a collection of blood capillary drops spotted and dried on to a
filter paper used for different bioanalysis. In comparison to conventional blood testing, DBS
offers practical, analytical, clinical and financial advantages. This less invasive sampling
is already used in infectious diseases screening and is useful for persons with poor venous
(babies, drug users or elderly). Mass-spectrometry-based analyses allow protein
quantification on very low amount of blood sample. In the project we combine the two
approaches to measure on DBS blood proteins with clinical relevance -including many FDA
approves biomarkers). The detection of the relevant clinical analytes will be validated on
available patient samples in accordance with the clinical norm ISO15189 and the requirement
for CE IVD marking. This will allow commercial developments (kits, protocols...) realized
with the industrial partner Spot-to-lab
Description:
Analyses of blood spotted and dried on a matrix (DBS), has been used since the 1960s in
clinical chemistry neonatal screening. Since then, many clinical analytes, including nucleic
acids, small molecules and lipids, have been successfully measured using DBS.
DBS collection is in fact less invasive than classical venous puncture, it can be carried out
by the patient at home and shipped by regular mail with no particular risk of contamination.
The use of DBS in routine for the detection of transmissible diseases, as well as for the
follow-up of chronic disease like diabetes, represent a safer and less costly evolution of
clinical biology for the society.
However the routine use of DBS is yet is limited. The major limitations of using DBS are
represented by the small blood volumes associated with DBS sampling (5-10 μL) and by the
limited possibility to detect peptides and proteins.
In this program, we will address this issue by adapting to DBS mass spectrometry (MS)
quantification of proteins/peptides. This relies on the detection of distinctive proteotypic
peptides (peptides which sequence is specific to a unique protein). The specificity of such
assays using triple quadrupole mass spectrometer is based on the capability to detect
peptides by three molecular characteristics: retention time, precursor ion mass (m/z) and
fragment ion mass (m/z). The combination of the precursor ion mass and the fragment ion mass
z, highly specific, is called a transition. This approach is named when several peptides are
detected in a single run "multiple reaction monitoring" or MRM. Using this approach, the
direct analysis of the trypsin digest of blood samples is possible without additional sample
fractionation.
In a series of preliminary experiments, we could detect on single DBS puch of 6mm of
diameter, 35 plasma proteins. Several proteins are of clinical relevance such as
apolipoprotein A, B, C, ceruloplasmin, haptoglobin, plasminogen, transthyretin (prealbumin)
or serum albumin. We will extend the range of blood protein detected by MS. Focus will be put
on select biomarkers to generate clinically relevant panels that can be used for patients
monitoring, nutrition monitoring and for the follow-up of frailty in elderly people .
Innovative workflows to obtain more rapid, efficient and costless detection will be
developed. We will also evaluate a new type of DBS card (Noviplex™) which collects plasma
instead of whole blood, and is expected to achieve better clinical concordance of the results
between DBS and classical sampling. The detection of the relevant clinical analytes will be
validated on available patient samples in accordance with the clinical norm ISO15189 and the
requirement for CE IVD marking. This will allow commercial developments (kits, protocols...)
realized with the industrial partner Spot-to-lab. This start-up has already put on the market
DBS analyses resulting from previous collaborative research. Being able to measure
peptide/proteins from DBS in parallel with other clinical analytes also developed by
Spot-To-Lab (vitamin D, HbA1c…) represents a breakthrough which will gives major perspective
to the use of DBS in clinical chemistry for disease detection and monitoring.
