CompletedNot Applicable

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

United Kingdom30 participantsStarted 2017-09-07

Plain-language 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.

Who can participate

Age range

18 Years – 45 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * Apparently healthy male or female individuals * Age 18-45 years old inclusive at screening * Body weight ≥ 45kg and BMI 18 -29.9 kg/m2 * Fasting LDL-C \< 4.1 mmol/l, TG \<1.7 mmol/l and HDL-C ≥ 1.0 mmol for men and ≥1.3 mmol for women * Palpable brachial arterial pulse, as per study team assessment * Not currently eligible for statin therapy according to current treatment criteria Exclusion Criteria: * History of established CV disease (Coronary Heart Disease, Cerebrovascular Disease, Peripheral Vascular Disease or Abdominal Aortic Aneurysm) * Lipid lowering treatment at screening or within 6 weeks before screening * Pregnancy at any study visit * Ongoing anticoagulation therapy with warfarin or any of the DOAC/NOAC's * History of hypersensitivity to any of the study drugs/any known sensitivity to alirocumab or monoclonal antibodies * History of alcohol or drug abuse or dependence within 6 months of the study at screening * Current or previous history of regular smoking (defined as 1 pack-year) within the last 10 years. * History of hypertension or sustained BP ≥140/90 mmHg on repeated measurements at screening * History of type 1 or 2 diabetes or HbA1c ≥ 48 mmol/mol (6.5%) at screening * Chronic kidney disease defined as eGFR \<60ml/min/1.73m2 at screening * Biological first-degree relatives who have experienced stroke, TIA, myocardial infarction or peripheral vascular disease (incident event at an age younger than: 55 for male and 65 for female rela…

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Forearm Blood Flow (FBF) - In response to intra-arterial Acetylcholine infusion, comparing Alirocumab to placebo.

Timeframe: 4 weeks

Trial details

NCT IDNCT03273972

SponsorCambridge University Hospitals NHS Foundation Trust

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2018-10-10

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