- To determine whether there is a mitigated immediate immune response to islet infusion in immunosuppressed recipients- To determine if complement activation during immediate immune response is affected in immunocompromised recipients
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
- Autoimmune disorders
- Endocrine gland therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Incremental increase of cytokines (i.e. TNF-alpha) in plasma after whole blood
exposure to allogeneic islets
Secondary outcome
Incremental increase of complement membrane attack complex (C5b-9) in plasma
after whole blood exposure to allogeneic islets
Incremental increase of islet associated blood markers (Micro-RNA*s, PPP1R1A)
in plasma after whole blood exposure to allogeneic islets
Incremental increase of cytokines (i.e. IL-1A and IL1B) in plasma after whole
blood exposure to allogeneic islets
Background summary
Islet transplantation is a highly technological intervention currently utilised
in patients with type 1 diabetes and related complications. Directly after
infusion of the islets, a substantial portion is destroyed by an immediately
occuring blood mediated immune reaction. This reaction occurs through several
pathways (including complement, coagulation and cytokinemediated pathways). The
current treatment to mitigate this acute inflammation is etanercept (TNF alpha
blockade), but this does not appear to be effect in islet-after-kidney patients
Study objective
- To determine whether there is a mitigated immediate immune response to islet
infusion in immunosuppressed recipients
- To determine if complement activation during immediate immune response is
affected in immunocompromised recipients
Study design
This is an in vitro experiment where fresh blood of three patient groups is
used. Around 20 mL of blood will be drawn from the participants, who are:
healthy controls, patients > 3 months after islet transplantation, and matched
controls with type 1 diabetes mellitus.
The drawing of blood will be timed with availability of isolated islets for
research.
The blood sample will then be divided in 15x 1 mL samples in 2 mL
heparin-coated reservoirs where either 500 IEQ islets + 100 µL medium or
control + 100 µL medium will be added. The samples will then be placed on a
rocking plate in a 37C incubator and for every time point a sample will be
taken off the plate, put on ice and centrifuged (at 4 gr C, 200G, 15 mins). The
supernatant will then be tested for immune response and islet damage markers.
The time points for taking the samples off the rocking plate are:
- 1 control sample before incubation
- T = +5 min, T = +15 min, +30 min, T = +60 min, T = +120 min, T = +240 min, T
= +360 min
The supernatant is tested for:
- A pro-inflammatory cytokine panel (i.e. TNF-alpha, IL-1a, IL-1b)
- Complement (i.e. C5b-9)
- Islet damage marker panel (i.e. microRNA kit, PPP1R1A)
Study burden and risks
THe burden consists of two venepunctures, which are conducted at moment agreed
by the researcher and the participant, when islets are available for research.
The extent of burden is considered to be low, since the risks of a venepuncture
are minimal, the amount of blood drawn is low (20 mL) en the procedure is
performed by a skilled professional
Albinusdreef 2
Leiden 2333ZA
NL
Albinusdreef 2
Leiden 2333ZA
NL
Listed location countries
Age
Inclusion criteria
Group 1: healthy volunteers, i.e. >18 years old and no current medication use except for over the counter drugs
Group 2: patients who are at least 3 months after transplantation
Group 3: patients with type 1 diabetes, matched for duration of diabetes with the patients in group 2
Exclusion criteria
Unable to give consent
Design
Recruitment
metc-ldd@lumc.nl
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 | NL55520.058.15 |