INTENSITY-LOW

  • Research type

    Research Study

  • Full title

    INvestigating the lowest Threshold of vascular bENefits from LDL cholesterol lowering with a PCSK9 mAb InhibiTor (alirocumab) in healthY volunteers – A mechanistic physiological study (INTENSITY-LOW)

  • IRAS ID

    223138

  • Contact name

    Joseph Cheriyan

  • Contact email

    jc403@medschl.cam.ac.uk

  • Sponsor organisation

    Cambridge University Hospitals NHS Foundation Trust and University of Cambridge

  • Duration of Study in the UK

    1 years, 7 months, 2 days

  • Research summary

    The INTENSITY-LOW study aims to answer if there are limits to LDL reduction in terms of 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 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 also hope to show that LDL cholesterol lowering via PCSK9 inhibition as a therapeutic intervention has effects which are comparable to that achieved with statins in terms of vascular function.

    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 the Alirocumab arm (which is a therapy designed to lower cholesterol) or comparison arm.

    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. The study will be open to recruitment for one year and the total study duration for each participant will be approximately 10 weeks. A series of non-invasive haemodynamic assessments and minimally invasive procedures including blood tests and forearm blood flow measurements will be conducted to determine if there is an improvement of nitric oxide bioavailability and reduced systemic inflammation. This study is funded by JP Moulton Charitable Foundation.

  • REC name

    East Midlands - Leicester South Research Ethics Committee

  • REC reference

    17/EM/0278

  • Date of REC Opinion

    23 Aug 2017

  • REC opinion

    Further Information Favourable Opinion