An interventional study of Written Informed Consent and Inclusion/Exclusion check in Atherosclerosis and Cardiovascular Diseases, sponsored by Cambridge University Hospitals NHS Foundation Trust. Completed at 1 site in United Kingdom. Open to participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-07-27.
Sponsored by Cambridge University Hospitals NHS Foundation Trust · Not applicable, Interventional, and Basic science
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.
1,517 studies on the registry are indexed under Atherosclerosis; 224 are open to participants now.
This study's enrollment of 30 is below the median of 100 across 879 interventional studies indexed under Atherosclerosis.
Browse Atherosclerosis studies →Cambridge University Hospitals NHS Foundation Trust is the lead sponsor of 171 studies on the registry; 37 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
TIA (transient ischaemic attack)
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
V2: Day 1 - Alirocumab 150mg (subcutaneous injection) V3: Day 15 +/- 3 days - Alirocumab 150mg (subcutaneous injection) plus Atorvastatin 20mg (oral) approx. 14 days prescription.
Other: Written Informed Consent · Other: Inclusion/Exclusion check · Other: Full Clinical Chemistry and Haematology Bloods · Other: Serum sample for systemic markers and lipid sub-fractions · Other: Pregnancy Test · Other: 12 Lead ECG · Other: Blood Pressure and Heart Rate · Other: Arterial Stiffness · Other: Central Haemodynamics · Other: Carotid Intima Media Thickness · Other: Forearm blood flow studies · Other: Concomitant medication check · Other: Medication compliance check (Pill count) · Other: Physical examination · Other: Medical history · Other: AE/SAE review & reporting · Drug: Dosing
V2: Day 1 - Placebo (subcutaneous injection) V3: Day 15 +/- 3 days - Placebo (subcutaneous injection) plus Atorvastatin 20mg (oral) approx. 14 days prescription.
Other: Written Informed Consent · Other: Inclusion/Exclusion check · Other: Full Clinical Chemistry and Haematology Bloods · Other: Serum sample for systemic markers and lipid sub-fractions · Other: Pregnancy Test · Other: 12 Lead ECG · Other: Blood Pressure and Heart Rate · Other: Arterial Stiffness · Other: Central Haemodynamics · Other: Carotid Intima Media Thickness · Other: Forearm blood flow studies · Other: Concomitant medication check · Other: Medication compliance check (Pill count) · Other: Physical examination · Other: Medical history · Other: AE/SAE review & reporting · Drug: Dosing
To be completed prior to conducting any study related procedures
Eligibility check
Participant required to fast for at least 6-8 hoursprior to visit. (Clear, non-caffeinated fluids are allowed)
Serum samples may be stored for later analysis.
If applicable for women of child bearing potential
participant resting supine
Measured in the seated position after 5 minutes rest
Measure of functional and structural changes which accompanies cardiovascular disease
Measure of functional and structural changes which accompanies cardiovascular disease
Measurements will be repeated three times, and the average of the median values will be recorded
Assess and determine vascular function, which can interrogate endothelium dependent and independent mechanisms of nitric oxide bioavailability
Review of medication taken by the participant
Ensure prescribed statin has been taken
Check overall health
Review of volunteers medial history
Monitor safety from the point of consent
To be performed at the end of the visit following completion all other study visits
Forearm Blood Flow (FBF) - In response to intra-arterial Acetylcholine infusion, comparing Alirocumab to placebo.
Change in FBF ratio, as measured by absolute \& percent change in venous occlusion plethysmography
Time frame: 4 weeks
Forearm Blood Flow in response to intra-arterial Acetylcholine infusion, comparing Alirocumab to statin.
Change in FBF ratio, as measured by absolute \& percent change in venous occlusion plethysmography
Time frame: 4 weeks
Forearm blood flow in response to intra-arterial Acetylcholine infusion, comparing Alirocumab with statin to statin alone.
Change in FBF ratio, as measured by absolute \& percent change in venous occlusion plethysmography
Time frame: 4 weeks
Forearm blood flow in response to intra-arterial Sodium Nitroprusside, comparing Alirocumab to placebo.
Change in FBF ratio, as measured by absolute \& percent change in venous occlusion plethysmography
Time frame: 4 weeks
Forearm blood flow in response to intra-arterial Sodium Nitroprusside, comparing Alirocumab to statin.
Change in FBF ratio, as measured by absolute \& percent change in venous occlusion plethysmography
Time frame: 4 weeks
Forearm blood flow in response to intra-arterial Sodium Nitroprusside, comparing Alirocumab with statin to statin alone.
Change in FBF ratio, as measured by absolute \& percent change in venous occlusion plethysmography
Time frame: 4 weeks
Forearm blood flow in response to intra-arterial L-NMMA infusion, comparing Alirocumab to placebo.
Change in FBF ratio, as measured by absolute \& percent change in venous occlusion plethysmography
Time frame: 4 weeks
Forearm blood flow in response to intra-arterial L-NMMA infusion, comparing Alirocumab to statin.
Change in FBF ratio, as measured by absolute \& percent change in venous occlusion plethysmography
Time frame: 4 weeks
Forearm blood flow in response to intra-arterial L-NMMA infusion, comparing Alirocumab with statin to statin alone.
Change in FBF ratio, as measured by absolute \& percent change in venous occlusion plethysmography
Time frame: 4 weeks
Total and LDL-cholesterol
Correlation of change in responses to Acetylcholine between groups.
Time frame: 4 weeks
Augmentation Index (an indicator of arterial stiffness)
Change in Augmentation Index between visits and different treatment regimes.
Time frame: 4 weeks
Pulse Wave Velocity
Change in aortic Pulse Wave Velocity between visits and different treatment regimes.
Time frame: 4 weeks
Carotid IMT
Change in Carotid IMT between visits and different treatment regimes.
Time frame: 4 weeks
Systemic inflammation
Change in lipid profile, hsCRP and other markers of systemic inflammation between visits and different treatment regimes.
Time frame: 4 weeks
Physical examination, vital signs, ECG, laboratory tests and adverse event assessment to determine Safety and tolerability parameters
Including physical examination, blood pressure, heart rate, 12-lead electrocardiograms (ECGs), clinical laboratory tests side effects and adverse event reporting.
Time frame: 4 weeks
Plan to share: No — Only the minimum required participant identifiable information (name and contact details) will be provided to the research team for the purpose of arranging study visits and completing the informed consent process. All delegated research personnel that is responsible to conduct the data/statistical analysis will only analyse data that is anonymised of any patient identifiable data.
No publications or documents are linked to this record.
This study is completed, as verified in Jul 2023. You cannot join it, but the record below documents what was studied.
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