Primary ObjectiveThe aim of this clinical part of the Body Barrier project is to produce data from metals that pass the mucosa-blood barrier and/or the blood-CFS barrier. The clinical data will be used to validate the multi-organ-on-chip platform to…
ID
Source
Brief title
Synonym
Health condition
om dierproeven te vervangen met een 'organ-on-chip' platform
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Blood and CSF handling and analysis (ACTA),(month 1-12): Blood (60) and CSF(41)
samples will be analysed to determine the concentrations of the metals using
ICP-MS, and compared with metals in dental and medical implants using ACTA*s
micro-sampling techniques, EDAX and SEM.
Correlation of clinical data with results obtained from the Body Barriers
platform (ACTA),(month 12-48): Determination of whether metals observed in
blood also pass the in vitro mucosa blood barrier into the microfluidics
compartment of the TissUse bioreactor chip. Determination of whether metals
observed in CSF are also detected passing the BBB of the Body Barriers platform
thus coming into contact with brain organoids
Deliverables/Milestones:
Completed analysis of metals in dental medical devices and correlation to blood
& CSF (month 12)
Correlation of clinical data with Body Barriers (month 48)
Secondary outcome
As a *by-product*, information is obtained about which metals from dental and
medical devices can be found in the peripheral blood and/or cerebrospinal fluid
(CSF).
Background summary
This project is part of the NWO project **Body Barriers**. The whole project
aims to develop a next generation *organ-on-chip* (OoC) platform that mimics
the functions of two of our important body barriers (i.e. mucosa-blood barrier
and blood-brain-interface, the blood-brain barrier resp. blood-CFS barrier) and
to establish Proof of Concept (POC) testing with metal leachables derived from
(dental) medical devices.
There is a wealth of data showing that some metals can pass the (oral) mucosal
barriers as well as the blood-brain-interface, such as mercury and nickel, and
so do metals leaching from medical devices (3-7). Metals and accumulation
thereof in the brain may induce oxidative stress, inflammation and
mitochondrial dysfunction, leading to neuronal dysfunction and consequent
neurodegeneration, as seen in Alzheimer*s disease, multiple sclerosis or
amyotrophic lateral sclerosis (ALS) (1,2). Our recent pilot data now indicates
that in the cerebrospinal fluid (CSF) of patients with Alzheimer*s disease,
enhanced levels of nickel and titanium compared to controls were detected,
indicating that such metals indeed penetrate the brain and may be associated
with neurodegeneration.
Study objective
Primary Objective
The aim of this clinical part of the Body Barrier project is to produce data
from metals that pass the mucosa-blood barrier and/or the blood-CFS barrier.
The clinical data will be used to validate the multi-organ-on-chip platform to
be developed in the Body barriers project .
Secondary Objective
As a *by-product*, information is obtained about which metals from dental and
medical devices can be found in the peripheral blood and/or cerebrospinal fluid
(CSF).
Study design
*Observational study*
Test groups
Patients referred to the Spaarne Gasthuis who will undergo orthopaedic surgery
(hip or knee implants), where spinal anaesthesia is indicated, will be asked to
participate in this study after they have been extensively informed about the
purpose of the study and the consequences for themselves.
Specific actions during the research
After inclusion and informed consent of patients, before undergoing the
surgical treatment, participants are invited for a consultation on ACTA. During
the consultation, an extensive medical and dental anamnesis will be taken, in
which an inventory is made of any medical devices applied in the mouth and any
medical devices present in the body. A micro-sample is optionally taken from
the metal-containing medical devices present in the mouth to evaluate the metal
composition. When dental implants have been applied and the patient does not
have an implant passport, the oral-implantologist will be contacted to find out
the brand and type of implant.
As part of the spinal anesthesia a small amount of CFS is aspirated to ensure
the needle tip has reached the spinal space.In this study (approx. 3 ml CFS
will be retracted and kept for this study. In addition, as part of the
anesthetic preparation, a small ampoule of blood (3-5 ml EDTA whole blood) may
be collected and used for further analysis in this study. Sample collection
will be done by Spaarne Gasthuis.
Study burden and risks
The extra burden for the patients only concerns the extra visit to ACTA
Gustav Mahlerlaan 3004
Amsterdam 1081LA
NL
Gustav Mahlerlaan 3004
Amsterdam 1081LA
NL
Listed location countries
Age
Inclusion criteria
Patients whose orthopedic surgery is planned and where it is decided to use
spinal anesthesia will be informed by the attending orthopedist in Spaarne
Gasthuis that they can participate in this study. They will be given the
information letter.
If they indicate an interest in participating in this study, their pre-surgery
anesthesia consultation will be combined with a consultation with the ACTA
researcher (at the Spaarne Gasthuis location). They will also be sent a bottle
to take morning urine. The researcher will give a verbal explanation of the
study, answer any questions and, if the patient wishes to participate, will
also perform an oral examination. The follow-up, collection of CSF and blood
will be performed during surgery.
Exclusion criteria
Age under 18 or above 80
Legally incompetent adults
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL82256.018.24 |