NCT03273972

INvestigating the Lowest Threshold of Vascular bENefits From LDL Lowering With a PCSK9 InhibiTor in healthY Volunteers

INvestigating the Lowest Threshold of Vascular bENefits From LDL Cholesterol Lowering With a PCSK9 mAb InhibiTor (Alirocumab) in healthY Volunteers

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 30 (actual)
• Sponsor: Cambridge University Hospitals NHS Foundation Trust · Academic / Other
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

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.

Conditions

• Atherosclerosis
• Cardiovascular Diseases

Interventions

Type	Name	Description
OTHER	Written Informed Consent	To be completed prior to conducting any study related procedures
OTHER	Inclusion/Exclusion check	Eligibility check
OTHER	Full Clinical Chemistry and Haematology Bloods	Participant required to fast for at least 6-8 hoursprior to visit. (Clear, non-caffeinated fluids are allowed)
OTHER	Serum sample for systemic markers and lipid sub-fractions	Serum samples may be stored for later analysis.
OTHER	Pregnancy Test	If applicable for women of child bearing potential
OTHER	12 Lead ECG	participant resting supine
OTHER	Blood Pressure and Heart Rate	Measured in the seated position after 5 minutes rest
OTHER	Arterial Stiffness	Measure of functional and structural changes which accompanies cardiovascular disease
OTHER	Central Haemodynamics	Measure of functional and structural changes which accompanies cardiovascular disease
OTHER	Carotid Intima Media Thickness	Measurements will be repeated three times, and the average of the median values will be recorded
OTHER	Forearm blood flow studies	Assess and determine vascular function, which can interrogate endothelium dependent and independent mechanisms of nitric oxide bioavailability
OTHER	Concomitant medication check	Review of medication taken by the participant
OTHER	Medication compliance check (Pill count)	Ensure prescribed statin has been taken
OTHER	Physical examination	Check overall health
OTHER	Medical history	Review of volunteers medial history
OTHER	AE/SAE review & reporting	Monitor safety from the point of consent
DRUG	Dosing	To be performed at the end of the visit following completion all other study visits

Timeline

• Start date: 2017-09-07
• Primary completion: 2018-10-10
• Completion: 2018-10-10
• First posted: 2017-09-06
• Last updated: 2023-07-27

Locations

1 site across 1 country: United Kingdom