AtherosclerosisPhase 4NCT02992301
Assessment of Atherosclerotic Plaque Characteristics Change by DCE-MRI With Alirocumab
A Phase 4 study testing Alirocumab in people with Atherosclerosis and Hyperlipidemia, run by Westside Medical Associates of Los Angeles at 1 site in United States.
Trial summary
Aim 1: To determine whether therapy with Alirocumab, compared to pre-treatment, will effectively improve carotid atherosclerotic plaque characteristics by reducing Ktrans and LRNC size. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Atherosclerosis, Hyperlipidemia
- What is being tested?
- Alirocumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2016to Nov 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Men and women ≥18 years of age.
- Subjects with documented inability to consistently take or tolerate high intensity statin therapy and LDL-C ≥70 mg/dL.
- Subjects are only able or allowed to take lower potency statin or low weekly dose of high potency statin due to concern of drug-to-drug interactions or lack of tolerance (pravastatin ≤140 mg, pitavastatin ≤14 mg, simvastatin ≤140 mg, atorvastatin ≤70 mg, or rosuvastatin ≤70 mg, weekly) or intolerant of all statin doses and with fasting LDL-C ≥100 mg/dL.
- Subjects must have significant carotid artery plaque with maximum wall thickness ≥2 mm on ultrasound performed within twelve months of screening.
- Subject must present with a LRNC on baseline MRI scan.
- Subjects must show an adequate image quality for MRI analysis.
- Medically stable.
- Willing to participate and sign informed consent.
Who cannot join
- Contraindication to MRI.
- Have immediate plans for bilateral carotid endarterectomy.
- Had received 2 or more doses of treatment with a PCSK9 inhibitor in the past 4 months.
- GFR ≤45 mL/min/1.73 m2 prior to MRI scan.
- Claustrophobia.
- Pregnant women; breastfeeding women; men and women of childbearing potential who are unwilling or unable to use a highly effective method of contraception.
Show all 12Show fewer
- TIA or stroke within the preceding twelve months
- Severe carotid stenosis in an asymptomatic patient defined as any one of the following:
- Greater than or equal to 70% luminal narrowing on any imaging modality
- Peak systolic velocity greater than or equal to 250 cm/second
- End diastolic velocity greater than or equal to 100 cm/second
- Systolic volume ratio greater than or equal to 3.5
Trial locations and contacts
1 site in 1 country.
United States1 site
Westside Medical Associates of Los Angeles
Beverly Hills, California, 90211
About this study
Official title: Assessment of Atherosclerotic Plaque Characteristics Change by DCE-MRI With Alirocumab - a Pilot Study
Aim 1: To determine whether therapy with Alirocumab, compared to pre-treatment, will effectively improve carotid atherosclerotic plaque characteristics by reducing Ktrans and LRNC size. To achieve this goal, we will (a) enroll 30 subjects who are intolerant to high intensity statin therapy and only able to tolerate low potency statin or low weekly dose of high potency statin and have LDL-C ≥70 mg/dl; (b) initiate alirocumab at 150mg subcutaneously injection every 2 weeks; (c) perform carotid DCE-MRI scans at baseline, 3, 6 and 12 months; (d) perform quantitative analysis for vascular inflammation and plaque LRNC volume and other plaque characteristics; (e) compare vascular inflammation and LRNC volume between pre- and post-alirocumab at 3, 6 and 12 months.
Aim 2: To examine associations between reductions in atherogenic lipids (LDL-C, Lp(a), non-HDL-C) and changes in atherosclerotic plaque characteristics. To achieve this goal, we will (a) perform laboratory assessments of lipids, lipoproteins and apo-lipoproteins at baseline and during the study; (b) compare lipids, lipoproteins and apo-lipoproteins levels between pre- and post-alirocumab; (c) correlate reductions in atherogenic lipids with changes atherosclerotic plaque characteristics.
Read the detailed description
Acute ischemic events caused by atherosclerosis cardiovascular disease (ASCVD) are primarily due to plaque rupture/erosion determined by plaque morphologic characteristics, local composition and inflammation, which can be directly assessed using magnetic resonance imaging (MRI). Prospective carotid MRI studies have demonstrated: (1) plaques with thin or ruptured cap, intraplaque hemorrhage (IPH), neovascularization, or larger lipid-rich necrotic core (LRNC) are strongly associated with occurrence of cerebrovascular and coronary events, (2) increased LRNC size is significantly associated with increased risk for systemic ASCVD events after adjusting for LDL-C or Non-HDL-C levels, (3) increased permeability of adventitial vasa vasorum is associated with presence of IPH which increases plaque burden and LRNC progression that appears to be resistant to conventional doses of statins, (4) intensive lipid therapy decreases carotid LRNC and vascular inflammation, (5) multicenter carotid studies can be conducted with good reproducibility and feasibility.
Unlike previous clinical trials evaluating carotid artery disease using ultrasound based technology that showed a weak relationship to systemic and coronary vascular events, recent studies have demonstrated predictive value of carotid plaque tissue characteristics for subsequent systemic ASCVD events including coronary events. Hellings and colleagues found that carotid plaque composition by histology in 818 patients who underwent endarterectomy is an independent predictor of future cardiovascular events during long-term post-operative follow-up. Specifically, those with carotid IPH and increased neovascularization were at significantly higher risk for ASCVD events. The Atherosclerosis Risk in Communities study investigators reported that carotid LRNC (HR=1.9, p=0.014) and minimum cap thickness (HR=0.67, p=0.03), as identified by MRI, were significantly associated with development of ASCVD including coronary events after adjusting for all clinical risk factors, treatment variables and biomarkers. The carotid MRI sub-study in AIM-HIGH showed that higher Lp(a) levels are associated with high-risk plaque features which are prevalent in subjects with established vascular disease and "well-controlled" LDL-C and blood pressure. Thin or ruptured cap and a larger LRNC are predictive of systemic ASCVD events that include 83% (15/18) of the coronary events in AIM-HIGH, meanwhile, none of the clinical risk factors and lipids were predictive of future events.
Alirocumab has shown substantial lowering in LDL-C, non-HDL-C and Lp(a), with or without concomitant statin treatment [43]. It has the potential to be a therapy that can improve plaque characteristics leading to reduction of ASCVD events. We propose to conduct a carotid MRI pilot study to demonstrate that adding alirocumab for 12 months, in comparison to pre-alirocumab therapy, in 30 subjects with documented carotid artery plaques who are not able to tolerate high intensity statin therapy and have LDL-C ≥70 mg/dl would improve atherosclerotic plaque characteristics by reducing Ktrans and LRNC size.
- Conditions
- Atherosclerosis, Hyperlipidemia
- Being tested
- Alirocumab
- Medical subject headings
- Atherosclerosis, Hyperlipidemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlirocumabDrug
Also called Praluent
Injectable prescription medicine called a PCSK9 inhibitor.
| Study group | Role | What they receive |
|---|---|---|
| Open Label | Experimental | All enrolled patients will receive open label Praluent (Alirocumab). Receives: Drug: Alirocumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in carotid atherosclerotic plaque characteristics as evidenced by effect on the volume transfer constant( Ktrans) and lipid-rich necrotic core (LRNC) size.
To determine whether therapy with Alirocumab, compared to pre-treatment, will effectively improve carotid atherosclerotic plaque characteristics by reducing Ktrans and LRNC size. To achieve this goal, we will (a) enroll 30 subjects who are intolerant to high intensity statin therpay and only able to tolerate low potency statin or low weekly dose of high potency statin and have LDL-C ≥100 mg/dl; (b) initiate alirocumab at 150mg subcutaneously injection every 2 weeks; (c) perform carotid DCE-MRI scans at baseline, 3, 6 and 12 months; (d) perform quantitative analysis for vascular inflammation (Ktrans) and plaque LRNC volume and other plaque characteristics; (e) compare Ktrans and LRNC volume between pre- and post-alirocumab at 3, 6 and 12 months.
Measured: 52 weeks
Secondary outcomes (1)
Associations between reductions in atherogenic lipids and changes in atherosclerotic plaque characteristics
To examine associations between reductions in atherogenic lipids (LDL-C, Lp(a), non-HDL-C) and changes in atherosclerotic plaque characteristics. To achieve this goal, we will (a) perform laboratory assessments of lipids, lipoproteins and apo-lipoproteins at baseline and during the study; (b) compare lipids, lipoproteins and apo-lipoproteins levels between pre- and post-alirocumab; (c) correlate reductions in atherogenic lipids with changes atherosclerotic plaque characteristics.
Measured: 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2016 (estimated)
- Study startNov 2016
- Primary completionNov 2019 (estimated)
- Study completionNov 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AtherosclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Westside Medical Associates of Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- University of Washington, Regeneron Pharmaceuticals
- Responsible party
- Principal investigator, Norman Lepor, MD, Westside Medical Associates of Los Angeles
- Investigators
- Norman Lepor, MD, Principal investigator, Westside Medical Associates of Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02992301
- Sponsor's protocol ID
- WMALA-99-032
- Status last verified
- Apr 2019
- First submitted
- 30 Nov 2016
- Last updated
- 26 Apr 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Atherosclerotic Plaque Characteristics Change by DCE-MRI With Alirocumab - a Pilot Study
- ClinicalTrials.gov ID
- NCT02992301
- Acronym / sponsor ID
- WMALA-99-032
- Conditions
- Atherosclerosis, Hyperlipidemia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Westside Medical Associates of Los AngelesUniversity, hospital or other
- Collaborators
- University of Washington, Regeneron Pharmaceuticals
- Study start
- Nov 2016 (actual)
- Primary completion
- Nov 2019 (estimated)
- Study completion
- Nov 2019 (estimated)
- First posted
- 14 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Aim 1: To determine whether therapy with Alirocumab, compared to pre-treatment, will effectively improve carotid atherosclerotic plaque characteristics by reducing Ktrans and LRNC size. To achieve this goal, we will (a) enroll 30 subjects who are intolerant to high intensity statin therapy and only able to tolerate low potency statin or low weekly dose of high potency statin and have LDL-C ≥70 mg/dl; (b) initiate alirocumab at 150mg subcutaneously injection every 2 weeks; (c) perform carotid DCE-MRI scans at baseline, 3, 6 and 12 months; (d) perform quantitative analysis for vascular inflammation and plaque LRNC volume and other plaque characteristics; (e) compare vascular inflammation and LRNC volume between pre- and post-alirocumab at 3, 6 and 12 months.
Aim 2: To examine associations between reductions in atherogenic lipids (LDL-C, Lp(a), non-HDL-C) and changes in atherosclerotic plaque characteristics. To achieve this goal, we will (a) perform laboratory assessments of lipids, lipoproteins and apo-lipoproteins at baseline and during the study; (b) compare lipids, lipoproteins and apo-lipoproteins levels between pre- and post-alirocumab; (c) correlate reductions in atherogenic lipids with changes atherosclerotic plaque characteristics.
Detailed description
Acute ischemic events caused by atherosclerosis cardiovascular disease (ASCVD) are primarily due to plaque rupture/erosion determined by plaque morphologic characteristics, local composition and inflammation, which can be directly assessed using magnetic resonance imaging (MRI). Prospective carotid MRI studies have demonstrated: (1) plaques with thin or ruptured cap, intraplaque hemorrhage (IPH), neovascularization, or larger lipid-rich necrotic core (LRNC) are strongly associated with occurrence of cerebrovascular and coronary events, (2) increased LRNC size is significantly associated with increased risk for systemic ASCVD events after adjusting for LDL-C or Non-HDL-C levels, (3) increased permeability of adventitial vasa vasorum is associated with presence of IPH which increases plaque burden and LRNC progression that appears to be resistant to conventional doses of statins, (4) intensive lipid therapy decreases carotid LRNC and vascular inflammation, (5) multicenter carotid studies can be conducted with good reproducibility and feasibility.
Unlike previous clinical trials evaluating carotid artery disease using ultrasound based technology that showed a weak relationship to systemic and coronary vascular events, recent studies have demonstrated predictive value of carotid plaque tissue characteristics for subsequent systemic ASCVD events including coronary events. Hellings and colleagues found that carotid plaque composition by histology in 818 patients who underwent endarterectomy is an independent predictor of future cardiovascular events during long-term post-operative follow-up. Specifically, those with carotid IPH and increased neovascularization were at significantly higher risk for ASCVD events. The Atherosclerosis Risk in Communities study investigators reported that carotid LRNC (HR=1.9, p=0.014) and minimum cap thickness (HR=0.67, p=0.03), as identified by MRI, were significantly associated with development of ASCVD including coronary events after adjusting for all clinical risk factors, treatment variables and biomarkers. The carotid MRI sub-study in AIM-HIGH showed that higher Lp(a) levels are associated with high-risk plaque features which are prevalent in subjects with established vascular disease and "well-controlled" LDL-C and blood pressure. Thin or ruptured cap and a larger LRNC are predictive of systemic ASCVD events that include 83% (15/18) of the coronary events in AIM-HIGH, meanwhile, none of the clinical risk factors and lipids were predictive of future events.
Alirocumab has shown substantial lowering in LDL-C, non-HDL-C and Lp(a), with or without concomitant statin treatment [43]. It has the potential to be a therapy that can improve plaque characteristics leading to reduction of ASCVD events. We propose to conduct a carotid MRI pilot study to demonstrate that adding alirocumab for 12 months, in comparison to pre-alirocumab therapy, in 30 subjects with documented carotid artery plaques who are not able to tolerate high intensity statin therapy and have LDL-C ≥70 mg/dl would improve atherosclerotic plaque characteristics by reducing Ktrans and LRNC size.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Open Label | Experimental | Drug: AlirocumabAll enrolled patients will receive open label Praluent (Alirocumab). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Men and women ≥18 years of age.
- Subjects with documented inability to consistently take or tolerate high intensity statin therapy and LDL-C ≥70 mg/dL.
- Subjects are only able or allowed to take lower potency statin or low weekly dose of high potency statin due to concern of drug-to-drug interactions or lack of tolerance (pravastatin ≤140 mg, pitavastatin ≤14 mg, simvastatin ≤140 mg, atorvastatin ≤70 mg, or rosuvastatin ≤70 mg, weekly) or intolerant of all statin doses and with fasting LDL-C ≥100 mg/dL.
- Subjects must have significant carotid artery plaque with maximum wall thickness ≥2 mm on ultrasound performed within twelve months of screening.
- Subject must present with a LRNC on baseline MRI scan.
Key exclusion criteria (12 listed)
- Contraindication to MRI.
- Have immediate plans for bilateral carotid endarterectomy.
- Had received 2 or more doses of treatment with a PCSK9 inhibitor in the past 4 months.
- GFR ≤45 mL/min/1.73 m2 prior to MRI scan.
- Claustrophobia.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlirocumabAlso: PraluentInjectable prescription medicine called a PCSK9 inhibitor. | Drug | Open Label |
Primary outcome
Changes in carotid atherosclerotic plaque characteristics as evidenced by effect on the volume transfer constant( Ktrans) and lipid-rich necrotic core (LRNC) size.
Time frame: 52 weeks
To determine whether therapy with Alirocumab, compared to pre-treatment, will effectively improve carotid atherosclerotic plaque characteristics by reducing Ktrans and LRNC size. To achieve this goal, we will (a) enroll 30 subjects who are intolerant to high intensity statin therpay and only able to tolerate low potency statin or low weekly dose of high potency statin and have LDL-C ≥100 mg/dl; (b) initiate alirocumab at 150mg subcutaneously injection every 2 weeks; (c) perform carotid DCE-MRI scans at baseline, 3, 6 and 12 months; (d) perform quantitative analysis for vascular inflammation (Ktrans) and plaque LRNC volume and other plaque characteristics; (e) compare Ktrans and LRNC volume between pre- and post-alirocumab at 3, 6 and 12 months.
1 secondary outcome
Associations between reductions in atherogenic lipids and changes in atherosclerotic plaque characteristics
Time frame: 52 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2019.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Norman Lepor, MD principal investigator
Westside Medical Associates of Los Angeles
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Alirocumab in people with Atherosclerosis and Hyperlipidemia, run by Westside Medical Associates of Los Angeles at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 26 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in carotid atherosclerotic plaque characteristics as evidenced by effect on the volume transfer constant( Ktrans) and lipid-rich necrotic core (LRNC) size. (time frame: 52 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Apr 2019.