to study the effect of everolimus (vs. mycophenolate) on dyslipidemia, ectopic fat accumulation, and cardiovascular function against a common calcineurin inhibitor (CNI) background.
ID
Source
Brief title
Condition
- Other condition
- Renal disorders (excl nephropathies)
Synonym
Health condition
transplantatie onderzoek
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Fasting serum lipid profile (LDLc, HDLc, TG, Total Cholesterol, lipoprotein
profile)
- Proton-magnetic resonance spectroscopy (1H-MRS) assessed ectopic lipid
accumulation in liver (primary) and heart (secondary).
- Non-contrast MR assessed visceral and subcutaneous adipose tissue (VAT, SAT)
- Non-contrast MR assessed cardiovascular function.
Secondary outcome
not applicable
Background summary
Long-term patient survival after kidney transplantation is limited by a seven
times higher risk of cardiovascular mortality in renal transplant recipients
(RTR) compared to the general population. Everolimus, an immunosuppressive drug
and mTOR-inhibitor with important anti-proliferative capacity, is associated
with significant hyperlipidemia, which limits its widespread use and which
seems contra-intuitive to presumed beneficial effects against atherosclerosis.
Precise pathways and consequences of mTOR-related hyperlipidemia remain
uncertain.
Hypothesis: Hyperlipidemia that is associated with mTOR inhibition in RTR
origins from a diminished ectopic lipid accumulation in nonadipose tissue (such
as liver and heart) and is associated with improved cardiovascular function.
Study objective
to study the effect of everolimus (vs. mycophenolate) on dyslipidemia, ectopic
fat accumulation, and cardiovascular function against a common calcineurin
inhibitor (CNI) background.
Study design
two-year observational study as local add-on of the TRANSFORM Study, a
randomized control trial in RTR (P13-233) of everolimus+CNI+steroids vs.
mycophenolate+CNI+steroids with assessments of main study parameters at 1 week
pretransplant, 1 and 2 years posttransplant.
Study burden and risks
Everolimus has anti-proliferative characteristics that may protect RTR from
their high risk of malignancies, viral infections, and cardiovascular disease.
However, dyslipidemia is a significant side effect of everolimus, which limits
its widespread use and which seems counterintuitive to the presumed beneficial
effects on cardiovascular disease. Presently, the clinical significance and
pathways of everolimus-induced dyslipidemia are unknown. We hypothesize that
everolimus induced-dyslipidemia is a bystander effect of a diminished ectopic
lipid accumulation in nonadipose tissue and thus associated with improved
cardiovascular and organ function. Gaining insight into the pathways and
consequences of mTOR-associated dyslipidemia may improve targeted therapy in
the future. The burden of participation in this study is limited. Subjects will
already participate in the TRANSFORM Study, and participants to this sub-study
will additionally have three noninvasive MRI measurements of approximately one
hour at 1 week before, and 1 and 2 years posttransplant in a fasting state.
Blood for fasting lipid spectrum will be withdrawn as well. The TRANSFROM Study
is a unique clinical setting to observe the effect of mTOR inhibition on
ectopic lipid accumulation in relation to dyslipidemia in humans.
Albinusdreef 2
Leiden 2333ZA
NL
Albinusdreef 2
Leiden 2333ZA
NL
Listed location countries
Age
Inclusion criteria
Renal transplant recipients from Leiden who will participate after informed consent in the global TRANSFORM Study (P13-233).
Exclusion criteria
Any standard contraindications for MRI or 1H-MRS (i.a. claustrophobia, metal parts, etc)
Design
Recruitment
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 | NL49252.058.14 |