INvestigating the Lowest Threshold of Vascular bENefits From LDL Lowering With a PCSK9 InhibiTor in healthY Volunteers
NCT ID: NCT03273972
Last Updated: 2023-07-27
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
NA
30 participants
INTERVENTIONAL
2017-09-07
2018-10-10
Brief Summary
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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.
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
Alirocumab treatment arm:
* V2: Alirocumab (150mg)
* V3: Alirocumab (150mg) \& Atorvastatin (20mg)
Comparator treatment arm
* V2: Placebo
* V3: Placebo \& Atorvastatin (20mg)
BASIC_SCIENCE
DOUBLE
CRF nurses will also have to collect and store medication in their building. Statin can be stored in a locked cupboard (open label).
Study Groups
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Alirocumab Treatment Arm
V2: Day 1 - Alirocumab 150mg (subcutaneous injection) V3: Day 15 +/- 3 days - Alirocumab 150mg (subcutaneous injection) plus Atorvastatin 20mg (oral) approx. 14 days prescription.
Written Informed Consent
To be completed prior to conducting any study related procedures
Inclusion/Exclusion check
Eligibility check
Full Clinical Chemistry and Haematology Bloods
Participant required to fast for at least 6-8 hoursprior to visit. (Clear, non-caffeinated fluids are allowed)
Serum sample for systemic markers and lipid sub-fractions
Serum samples may be stored for later analysis.
Pregnancy Test
If applicable for women of child bearing potential
12 Lead ECG
participant resting supine
Blood Pressure and Heart Rate
Measured in the seated position after 5 minutes rest
Arterial Stiffness
Measure of functional and structural changes which accompanies cardiovascular disease
Central Haemodynamics
Measure of functional and structural changes which accompanies cardiovascular disease
Carotid Intima Media Thickness
Measurements will be repeated three times, and the average of the median values will be recorded
Forearm blood flow studies
Assess and determine vascular function, which can interrogate endothelium dependent and independent mechanisms of nitric oxide bioavailability
Concomitant medication check
Review of medication taken by the participant
Medication compliance check (Pill count)
Ensure prescribed statin has been taken
Physical examination
Check overall health
Medical history
Review of volunteers medial history
AE/SAE review & reporting
Monitor safety from the point of consent
Dosing
To be performed at the end of the visit following completion all other study visits
Comparator Treatment Arm
V2: Day 1 - Placebo (subcutaneous injection) V3: Day 15 +/- 3 days - Placebo (subcutaneous injection) plus Atorvastatin 20mg (oral) approx. 14 days prescription.
Written Informed Consent
To be completed prior to conducting any study related procedures
Inclusion/Exclusion check
Eligibility check
Full Clinical Chemistry and Haematology Bloods
Participant required to fast for at least 6-8 hoursprior to visit. (Clear, non-caffeinated fluids are allowed)
Serum sample for systemic markers and lipid sub-fractions
Serum samples may be stored for later analysis.
Pregnancy Test
If applicable for women of child bearing potential
12 Lead ECG
participant resting supine
Blood Pressure and Heart Rate
Measured in the seated position after 5 minutes rest
Arterial Stiffness
Measure of functional and structural changes which accompanies cardiovascular disease
Central Haemodynamics
Measure of functional and structural changes which accompanies cardiovascular disease
Carotid Intima Media Thickness
Measurements will be repeated three times, and the average of the median values will be recorded
Forearm blood flow studies
Assess and determine vascular function, which can interrogate endothelium dependent and independent mechanisms of nitric oxide bioavailability
Concomitant medication check
Review of medication taken by the participant
Medication compliance check (Pill count)
Ensure prescribed statin has been taken
Physical examination
Check overall health
Medical history
Review of volunteers medial history
AE/SAE review & reporting
Monitor safety from the point of consent
Dosing
To be performed at the end of the visit following completion all other study visits
Interventions
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Written Informed Consent
To be completed prior to conducting any study related procedures
Inclusion/Exclusion check
Eligibility check
Full Clinical Chemistry and Haematology Bloods
Participant required to fast for at least 6-8 hoursprior to visit. (Clear, non-caffeinated fluids are allowed)
Serum sample for systemic markers and lipid sub-fractions
Serum samples may be stored for later analysis.
Pregnancy Test
If applicable for women of child bearing potential
12 Lead ECG
participant resting supine
Blood Pressure and Heart Rate
Measured in the seated position after 5 minutes rest
Arterial Stiffness
Measure of functional and structural changes which accompanies cardiovascular disease
Central Haemodynamics
Measure of functional and structural changes which accompanies cardiovascular disease
Carotid Intima Media Thickness
Measurements will be repeated three times, and the average of the median values will be recorded
Forearm blood flow studies
Assess and determine vascular function, which can interrogate endothelium dependent and independent mechanisms of nitric oxide bioavailability
Concomitant medication check
Review of medication taken by the participant
Medication compliance check (Pill count)
Ensure prescribed statin has been taken
Physical examination
Check overall health
Medical history
Review of volunteers medial history
AE/SAE review & reporting
Monitor safety from the point of consent
Dosing
To be performed at the end of the visit following completion all other study visits
Eligibility Criteria
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Inclusion Criteria
* 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
* 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 relatives)
* History of autoimmune inflammatory conditions
* Lack of ability to provide informed consent
* TSH \>5.0 mu/l at screening
* Clinically significant liver disease on the basis of screening bloods or history
* History of myositis/rhabdomyolysis
* Any concomitant condition that, at the discretion of the investigator, may affect the participants' ability to complete the study or the study results
18 Years
45 Years
ALL
Yes
Sponsors
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University of Cambridge
OTHER
Cambridge University Hospitals NHS Foundation Trust
OTHER
Responsible Party
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Joseph Cheriyan, MD
Consultant Physician & Clinical Pharmacologist/Associate Lecturer
Principal Investigators
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Joseph Cheriyan, MBChB, FRCP, MA
Role: PRINCIPAL_INVESTIGATOR
Cambridge University Hospitals NHS Trust
Michalis Kostapanos, MD, PhD, FRSPH
Role: PRINCIPAL_INVESTIGATOR
Cambridge University Hospitals NHS Trust
Locations
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Addenbrooke's Hospital
Cambridge, Cambridgeshire, United Kingdom
Countries
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Other Identifiers
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INTENSITY-LOW
Identifier Type: -
Identifier Source: org_study_id
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