INvestigating the Lowest Threshold of Vascular bENefits From LDL Lowering With a PCSK9 InhibiTor in healthY Volunteers
Status:
Completed
Trial end date:
2018-10-10
Target enrollment:
Participant gender:
Summary
The INTENSITY-LOW study aims to answer if there are any limits to LDL reduction in relation
to benefitting vascular health from a mechanistic viewpoint, and therefore potentially
limitations to primary prevention in healthy volunteers by lowering LDL cholesterol using
PCSK9 therapies. This research is being carried out because it is unclear what the lowest
threshold of LDL cholesterol should be to attain significant reductions in CV risk in healthy
individuals. It is also unknown whether there is a true limit of LDL cholesterol below which
there is no further improvement in endothelial function in healthy people, and, whether this
is associated with a reduction in markers of both systemic and vascular inflammation. This
study will hope to provide evidence that the so-called pleiotropic effects of statins are
actually mediated by a mechanism of LDL-cholesterol lowering per se and not necessarily a
special therapeutic effect of statins.
Defining this may help identify individuals from the general population who may benefit from
more aggressive lipid-lowering treatment than standard statin treatment in terms of CV
morbidity and mortality.
This study will be conducted in healthy volunteers only, where participants will be
randomized to either the Alirocumab arm (which is a therapy designed to lower cholesterol) or
comparator arm. Both Alirocumab and comparator arms will be combined with Atorvastatin
(another therapy designed to lower cholesterol) at the second dosing visit.
In total, thirty healthy individuals will be recruited to this single centre, randomized,
single blind, parallel group, mechanistic physiological study which will be conducted at
Cambridge University Hospitals NHS Foundation Trust/University of Cambridge. This study will
be open to recruitment for one year and the total study duration for each participant will be
approximately 10 weeks. There will be 4 study visits in total with a telephone follow up at
the end of the study. Of these visits, two will be dosing visits and the total duration of
treatment is approx. 4 weeks.
A series of non-invasive haemodynamic assessments and minimally invasive procedures including
blood tests and forearm blood flow measurements will be conducted prior, during and post
dosing to determine if there is an improvement of endothelia vascular function (as measured
by nitric oxide bioavailability) and reduced systemic inflammation. This study is funded by
JP Moulton Charitable Foundation.
Phase:
N/A
Details
Lead Sponsor:
Cambridge University Hospitals NHS Foundation Trust