Microfluidics and Transcriptomics in Post Solid Organ Transplant Patients
| Status: | Recruiting |
|---|---|
| Conditions: | Infectious Disease |
| Therapuetic Areas: | Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 18 - 70 |
| Updated: | 11/10/2018 |
| Start Date: | July 2016 |
| End Date: | July 2019 |
| Contact: | Ali Zarrinpar, MD, PhD |
| Email: | Ali.Zarrinpar@surgery.ufl.edu |
The Use of Microfluidics and Transcriptomics to Implement Precision Medicine in Post Solid Organ Transplant Patients
The field of genomics is an exciting new field being applied in medicine. Its use in treating
some cancers, sepsis and burn patients has been very promising. As knowledge of genomics and
application of microarrays expands, researchers are developing more intelligent ways to
provide individualized care for patients. The plan of this research study is to apply the use
of genomics as a tool for transplant in several capacities.
This research study is designed to develop methods of isolating relevant cell types via
microarray plates, then extracting mRNA samples of those cell types and capturing their
genetic profile. This will be done with the blood of up to ten healthy donors. Once this
ability has been demonstrated, the next step will be to use these testing in several
capacities in transplant patients. The research study plan involves following the genetic
profile of 26 kidney transplant patients. One group will be followed prospectively starting
at baseline, and then at various set time points. A second group will be sampled with the
occurrence of clinical events. These events include viral, bacterial, and fungal infection,
WBC < 2.5 or biopsy proven rejection episodes or normal graft function. Thus, the intention
of the study is to demonstrate how immunosuppression alters the expression of this genetic
expression of these T cells. In doing so, the study will provide a better understanding of
the specific and true immunosuppressed state for any given patient.
some cancers, sepsis and burn patients has been very promising. As knowledge of genomics and
application of microarrays expands, researchers are developing more intelligent ways to
provide individualized care for patients. The plan of this research study is to apply the use
of genomics as a tool for transplant in several capacities.
This research study is designed to develop methods of isolating relevant cell types via
microarray plates, then extracting mRNA samples of those cell types and capturing their
genetic profile. This will be done with the blood of up to ten healthy donors. Once this
ability has been demonstrated, the next step will be to use these testing in several
capacities in transplant patients. The research study plan involves following the genetic
profile of 26 kidney transplant patients. One group will be followed prospectively starting
at baseline, and then at various set time points. A second group will be sampled with the
occurrence of clinical events. These events include viral, bacterial, and fungal infection,
WBC < 2.5 or biopsy proven rejection episodes or normal graft function. Thus, the intention
of the study is to demonstrate how immunosuppression alters the expression of this genetic
expression of these T cells. In doing so, the study will provide a better understanding of
the specific and true immunosuppressed state for any given patient.
The two specific aims of the research study are as follows: 1) Proof of concept with two
parts. Firstly, the study plan is to prove that T cells that are very commonly involved in
the immune response: CD2, CD3, CD4, and CD8 populations can be captured. These cells will be
captured, lysed and their mRNA genomics will be mapped. The second part of the proof of
concept will involve exposing the CD2, CD3, CD4 and CD8 populations ex vivo to various serum
concentrations of tacrolimus - the main cornerstone immunosuppressive medication in solid
organ transplant. Exposure of the three cell types to the various tacrolimus concentrations
will demonstrate that there is testing that can detect mRNA transcripts corresponding to
under, optimal and over immunosuppressed states. The quantify IL2 production of the three
cell types under the various immunosuppressive conditions will then be measured. With these 2
parts of the first specific aim of the study, a technique that can readily and easily isolate
the cell populations of interest from the transplant patients and can capture how these cell
populations respond to immunosuppression at various concentrations will have been
demonstrated. 2) The second specific aim of the research study is running this genomic
profiling on kidney transplant recipients. For this portion of the study, there will be two
cohorts. A cohort identified as the "prospective" group and a cohort labeled as the "event"
group. For the prospective cohort, blood will be obtained from the patients at specific time
points. Specifically, blood samples will be obtained in the pre-transplant setting when the
patients present to the hospital for their transplant, then at post-kidney transplant day 0,
1, 2, 3 and 7 (+/- 1 day) and at day 14, 21, and 28 (+/-3 days). Blood samples will be
obtained again at months 2, 3, 6, 9, and 12 (+/- 1 week ). For the second group, blood
samples will be obtained at the time of "events", such as rejection, infection, etc., and
apply the same series of tests to their blood. For this group, blood draws will be done at
time 0(+/-1 day), at then at one week (+/-2 days), and at one, two and three months (+/-1
week) post time 0. There will be five blood samples collected per patient. For all patients,
there will be a comparison of the standard collected clinical information on the patient -
graft function, rejection, infection, immunosuppression levels - to the results of our
transcriptomics. The culmination of the project will involve revealing how genomics of the
specific types of T cells can more precisely reflect a patient's true immunosuppressed state
by corresponding to high, optimal and low immunosuppressive clinical phenotypes, and thus
allow transplant clinicians to more intelligently and accurately administer immunosuppressive
medications.
This study will involve obtaining blood samples on the kidney transplant patients at the time
in which they would otherwise have blood collected for standard clinical care. Consent will
be obtained for the testing on their blood, but the patients will not suffer any additional
pain or inconvenience of the testing. In coordination with the equipment and supplies
currently being used by the trauma and critical care department's research, the investigators
will organize the collection and running of the labs in a time efficient and minimally
expensive way
parts. Firstly, the study plan is to prove that T cells that are very commonly involved in
the immune response: CD2, CD3, CD4, and CD8 populations can be captured. These cells will be
captured, lysed and their mRNA genomics will be mapped. The second part of the proof of
concept will involve exposing the CD2, CD3, CD4 and CD8 populations ex vivo to various serum
concentrations of tacrolimus - the main cornerstone immunosuppressive medication in solid
organ transplant. Exposure of the three cell types to the various tacrolimus concentrations
will demonstrate that there is testing that can detect mRNA transcripts corresponding to
under, optimal and over immunosuppressed states. The quantify IL2 production of the three
cell types under the various immunosuppressive conditions will then be measured. With these 2
parts of the first specific aim of the study, a technique that can readily and easily isolate
the cell populations of interest from the transplant patients and can capture how these cell
populations respond to immunosuppression at various concentrations will have been
demonstrated. 2) The second specific aim of the research study is running this genomic
profiling on kidney transplant recipients. For this portion of the study, there will be two
cohorts. A cohort identified as the "prospective" group and a cohort labeled as the "event"
group. For the prospective cohort, blood will be obtained from the patients at specific time
points. Specifically, blood samples will be obtained in the pre-transplant setting when the
patients present to the hospital for their transplant, then at post-kidney transplant day 0,
1, 2, 3 and 7 (+/- 1 day) and at day 14, 21, and 28 (+/-3 days). Blood samples will be
obtained again at months 2, 3, 6, 9, and 12 (+/- 1 week ). For the second group, blood
samples will be obtained at the time of "events", such as rejection, infection, etc., and
apply the same series of tests to their blood. For this group, blood draws will be done at
time 0(+/-1 day), at then at one week (+/-2 days), and at one, two and three months (+/-1
week) post time 0. There will be five blood samples collected per patient. For all patients,
there will be a comparison of the standard collected clinical information on the patient -
graft function, rejection, infection, immunosuppression levels - to the results of our
transcriptomics. The culmination of the project will involve revealing how genomics of the
specific types of T cells can more precisely reflect a patient's true immunosuppressed state
by corresponding to high, optimal and low immunosuppressive clinical phenotypes, and thus
allow transplant clinicians to more intelligently and accurately administer immunosuppressive
medications.
This study will involve obtaining blood samples on the kidney transplant patients at the time
in which they would otherwise have blood collected for standard clinical care. Consent will
be obtained for the testing on their blood, but the patients will not suffer any additional
pain or inconvenience of the testing. In coordination with the equipment and supplies
currently being used by the trauma and critical care department's research, the investigators
will organize the collection and running of the labs in a time efficient and minimally
expensive way
Inclusion Criteria:
Healthy Controls
- consent for blood draw
Kidney Transplant Group
- actively listed with the University of Florida Kidney Transplant Program (which has
its own standards for active listing including not being pregnant),
- consent for blood draw
Exclusion criteria:
Healthy Control
- pregnancy,
- any known organ failure
Kidney Transplant Group
- none, exclusive to what is listed in inclusion criteria.
We found this trial at
1
site
University of Florida The University of Florida (UF) is a major, public, comprehensive, land-grant, research...
Click here to add this to my saved trials
