Atherosclerotic Cardiovascular DiseaseINSPIRARNCT05720156
Immunomodulatory Effects of PCSK9 Inhibition
An observational study of Atherosclerotic Cardiovascular Disease and Cardiovascular Diseases, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
Cardiovascular disease (CVD) represents the leading cause of death worldwide. While medications, such as statins, significantly reduce atherosclerotic CVD (ASCVD) risk by lowering low density lipoprotein levels, they may also have pleiotropic effects on inflammation. Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Atherosclerotic Cardiovascular Disease, Cardiovascular Diseases, Atherosclerosis
- What is being tested?
- 99mTc-tilmanocept SPECT/CT scanning
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Apr 2024to Mar 2026
- Phase
- Observational
- 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 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Case: People with known ASCVD, on high-intensity statin therapy for at least 6 months and about to initiate PCSK9 inhibitor therapy Control: Healthy controls with no known ASCVD and not on statin
Who may be able to join
- 18 to 85 years of age
- CASE PARTICIPANTS ONLY: History of ASCVD (including a history of coronary artery disease, carotid artery disease, peripheral artery disease, acute coronary syndrome, percutaneous coronary intervention, coronary bypass surgery, carotid endarterectomy, stroke or TIA)
- CASE PARTICIPANTS ONLY: High-intensity statin therapy for at least 6 months prior enrollment and without an interruption of >1 month
- CASE PARTICIPANTS ONLY: Initiation of PCSK9 inhibition with either evolocumab or alirocumab (and not inclisiran - PSCK9 inhibition through small interfering RNA)
Who cannot join
- pregnancy or breastfeeding
- CONTROL PARTICIPANTS ONLY: No known history of ASCVD (including a history of coronary artery disease, carotid artery disease, peripheral artery disease, acute coronary syndrome, percutaneous coronary intervention, coronary bypass surgery, carotid endarterectomy, stroke or TIA)
- current treatment with prescription, systemic (oral, IV, IM or intra-articular) steroids or anti-inflammatory/immune suppressant medical therapies (excluding topical therapies, UV therapy, ASA-derivative therapies, or NSAIDS) for autoimmune/inflammatory diseases (psoriasis, RA, IBD, lupus), post-transplant care, asthma, or pain syndromes
- use of oral steroids or prescription oral anti-inflammatory/immune suppressant medication for > 7 days within the past 1 month
- use of IV, IM or intra-articular steroids or IV, IM or intra-articular anti-inflammatory/immune suppressant medication within the past 3 months
- Any prior use of PCSK9 inhibitors including both monoclonal antibodies or small interfering RNA
Show all 10Show fewer
- CONTROL PARTICIPANTS ONLY: use of cholesterol lowering therapy (including statins, ezetimibe, bempedoic acid, PCSK9 inhibitors including both monoclonal antibodies or small interfering RNA, niacin, fibrates) or other lipid lowering agents associated with ASCVD risk reduction such as Vascepa. Cholesterol lowering therapies that that predominantly target triglycerides including over the counter omega-3 fatty acids and Lovaza are permitted.
- known allergy to dextrans and/or DTPA and/or radiometals
- significant radiation exposure (>2 CT angiograms) received within the past 12 months
- concurrent enrollment in another research study judged by the study investigators to interfere with the current study
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: ImmuNomodulatory EffectS of PCSK9 Inhibition: A TaRgeted Molecular Imaging AppRoach
Cardiovascular disease (CVD) represents the leading cause of death worldwide. While medications, such as statins, significantly reduce atherosclerotic CVD (ASCVD) risk by lowering low density lipoprotein levels, they may also have pleiotropic effects on inflammation. The immunomodulatory effects of these medications are relevant to ASCVD risk reduction given that inflammation plays a central role in atherosclerotic plaque formation (atherogenesis) and influences the development of vulnerable plaque morphology. Patients on statins, however, may have residual inflammation contributing to incident ASCVD despite the potent LDL-lowering effects of statins. While new therapies, such as proprotein convertase subtilisin/kexin type 9 (PSCK9) inhibitors, further reduce incident ASCVD and drastically reduce LDL-C below that achieved by statin therapy alone, PCSK9 inhibitors may also have pleiotropic effects on inflammation. Thus, PCSK9 inhibitors may help reduce arterial inflammation to a level closer to that of patients without ASCVD. This study will apply a novel targeted molecular imaging approach, technetium 99m (99mTc)-tilmanocept SPECT/CT, to determine if residual macrophage-specific arterial inflammation is present with statin therapy and the immunomodulatory effects of PSCK9 inhibition. Given the continued high mortality and morbidity attributable to ASCVD, strong imperatives exist to better understand the immunomodulatory effects of lipid lowering therapies and residual inflammatory risk. This understanding, in turn, will inform the development of new ASCVD preventative and treatment strategies as well as elucidate other indications for established therapies.
- Conditions
- Atherosclerotic Cardiovascular Disease, Cardiovascular Diseases, Atherosclerosis, Arterial Inflammation, Vascular Diseases, Vascular Disease, Peripheral
- Being tested
- 99mTc-tilmanocept SPECT/CT scanning
- Medical subject headings
- Atherosclerosis, Cardiovascular Diseases, Arteritis, Vascular Diseases, Peripheral Vascular Diseases, Vascular Calcification, Hypercholesterolemia, Hyperlipidemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
99mTc-tilmanocept SPECT/CT scanningOther
99mTc-Tilmanocept SPECT/CT allows for visualization of macrophage-specific arterial infiltration
| Study group | Role | What they receive |
|---|---|---|
| Case group: History of ASCVD, on high-intensity statins and initiating PCSK9 inhibitor therapy | History of ASCVD, on high-intensity statins and initiating PCSK9 inhibitor therapy Receives: Other: 99mTc-tilmanocept SPECT/CT scanning | |
| Control group: No history of ASCVD, not on statins or initiating PCSK9 inhibitor therapy | No history of ASCVD, not currently on high-intensity statins, other lipid lowering therapy or initiating PCSK9 inhibitor therapy Receives: Other: 99mTc-tilmanocept SPECT/CT scanning |
What is being measured
The primary outcome is the main question the study is designed to answer.
Between-group difference (case participants versus control participants) in percent volume with aortic 99mTc-tilmanocept uptake across different uptake thresholds
Measured: Baseline
Change in the percent volume with aortic 99mTc-tilmanocept uptake across different uptake thresholds after PCSK9 inhibitor therapy for 12 months (case participants only)
Measured: Baseline and 12 Months
Secondary outcomes (6)
Relationship between baseline immune cell subpopulations (cells/µL) and aortic volume with 99mTc-tilmanocept uptake
Measured: Baseline and 12 Months
Relationship between baseline markers of immune activation/ systemic inflammation and aortic volume with 99mTc-tilmanocept uptake
Measured: Baseline and 12 Months
Relationship between change in macrophage-specific arterial infiltration with PCSK9 inhibitors and change in immune cell subpopulations (cells/µL)
Measured: Baseline and 12 Months
Relationship between change in macrophage-specific arterial infiltration with PCSK9 inhibitors and change in markers of immune activation/ systemic inflammation
Measured: Baseline and 12 Months
Relationship between change in macrophage-specific arterial infiltration with PCSK9 inhibitors and baseline immune cell subpopulations (cells/µL)
Measured: Baseline and 12 Months
Relationship between change in macrophage-specific arterial infiltration with PCSK9 inhibitors and baseline markers of immune activation/ systemic inflammation
Measured: Baseline and 12 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2023
- Study start4 Apr 2024
- Primary completionMar 2026 (estimated)
- Study completionMar 2026 (estimated)
Why it stopped: Lack of Feasibility
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atherosclerotic Cardiovascular DiseaseStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mabel Toribio, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05720156
- Sponsor's protocol ID
- 2022P002214
- Acronym
- INSPIRAR
- Status last verified
- Sep 2025
- First submitted
- 20 Jan 2023
- Last updated
- 26 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ImmuNomodulatory EffectS of PCSK9 Inhibition: A TaRgeted Molecular Imaging AppRoach
- ClinicalTrials.gov ID
- NCT05720156
- Acronym / sponsor ID
- INSPIRAR / 2022P002214
- Conditions
- Atherosclerotic Cardiovascular Disease, Cardiovascular Diseases, Atherosclerosis, Arterial Inflammation, Vascular Diseases, Vascular Disease, Peripheral
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: Lack of Feasibility
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- 4 Apr 2024 (actual)
- Primary completion
- Mar 2026 (estimated)
- Study completion
- Mar 2026 (estimated)
- First posted
- 9 Feb 2023 (actual)
- 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.
Cardiovascular disease (CVD) represents the leading cause of death worldwide. While medications, such as statins, significantly reduce atherosclerotic CVD (ASCVD) risk by lowering low density lipoprotein levels, they may also have pleiotropic effects on inflammation. The immunomodulatory effects of these medications are relevant to ASCVD risk reduction given that inflammation plays a central role in atherosclerotic plaque formation (atherogenesis) and influences the development of vulnerable plaque morphology. Patients on statins, however, may have residual inflammation contributing to incident ASCVD despite the potent LDL-lowering effects of statins. While new therapies, such as proprotein convertase subtilisin/kexin type 9 (PSCK9) inhibitors, further reduce incident ASCVD and drastically reduce LDL-C below that achieved by statin therapy alone, PCSK9 inhibitors may also have pleiotropic effects on inflammation. Thus, PCSK9 inhibitors may help reduce arterial inflammation to a level closer to that of patients without ASCVD. This study will apply a novel targeted molecular imaging approach, technetium 99m (99mTc)-tilmanocept SPECT/CT, to determine if residual macrophage-specific arterial inflammation is present with statin therapy and the immunomodulatory effects of PSCK9 inhibition. Given the continued high mortality and morbidity attributable to ASCVD, strong imperatives exist to better understand the immunomodulatory effects of lipid lowering therapies and residual inflammatory risk. This understanding, in turn, will inform the development of new ASCVD preventative and treatment strategies as well as elucidate other indications for established therapies.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Case group: History of ASCVD, on high-intensity statins and initiating PCSK9 inhibitor therapy | – | Other: 99mTc-tilmanocept SPECT/CT scanningHistory of ASCVD, on high-intensity statins and initiating PCSK9 inhibitor therapy |
| Control group: No history of ASCVD, not on statins or initiating PCSK9 inhibitor therapy | – | Other: 99mTc-tilmanocept SPECT/CT scanningNo history of ASCVD, not currently on high-intensity statins, other lipid lowering therapy or initiating PCSK9 inhibitor therapy |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Case: People with known ASCVD, on high-intensity statin therapy for at least 6 months and about to initiate PCSK9 inhibitor therapy Control: Healthy controls with no known ASCVD and not on statin
Key inclusion criteria (4 listed)
- 18 to 85 years of age
- CASE PARTICIPANTS ONLY: History of ASCVD (including a history of coronary artery disease, carotid artery disease, peripheral artery disease, acute coronary syndrome, percutaneous coronary intervention, coronary bypass surgery, carotid endarterectomy, stroke or TIA)
- CASE PARTICIPANTS ONLY: High-intensity statin therapy for at least 6 months prior enrollment and without an interruption of >1 month
- CASE PARTICIPANTS ONLY: Initiation of PCSK9 inhibition with either evolocumab or alirocumab (and not inclisiran - PSCK9 inhibition through small interfering RNA)
Key exclusion criteria (10 listed)
- pregnancy or breastfeeding
- CONTROL PARTICIPANTS ONLY: No known history of ASCVD (including a history of coronary artery disease, carotid artery disease, peripheral artery disease, acute coronary syndrome, percutaneous coronary intervention, coronary bypass surgery, carotid endarterectomy, stroke or TIA)
- current treatment with prescription, systemic (oral, IV, IM or intra-articular) steroids or anti-inflammatory/immune suppressant medical therapies (excluding topical therapies, UV therapy, ASA-derivative therapies, or NSAIDS) for autoimmune/inflammatory diseases (psoriasis, RA, IBD, lupus), post-transplant care, asthma, or pain syndromes
- use of oral steroids or prescription oral anti-inflammatory/immune suppressant medication for > 7 days within the past 1 month
- use of IV, IM or intra-articular steroids or IV, IM or intra-articular anti-inflammatory/immune suppressant medication within the past 3 months
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 |
|---|---|---|
| 99mTc-tilmanocept SPECT/CT scanning99mTc-Tilmanocept SPECT/CT allows for visualization of macrophage-specific arterial infiltration | Other | Case group: History of ASCVD, on high-intensity statins and initiating PCSK9 inhibitor therapy, Control group: No history of ASCVD, not on statins or initiating PCSK9 inhibitor therapy |
Primary outcome
Between-group difference (case participants versus control participants) in percent volume with aortic 99mTc-tilmanocept uptake across different uptake thresholds
Time frame: Baseline
Change in the percent volume with aortic 99mTc-tilmanocept uptake across different uptake thresholds after PCSK9 inhibitor therapy for 12 months (case participants only)
Time frame: Baseline and 12 Months
6 secondary outcomes
Relationship between baseline immune cell subpopulations (cells/µL) and aortic volume with 99mTc-tilmanocept uptake
Time frame: Baseline and 12 Months
Relationship between baseline markers of immune activation/ systemic inflammation and aortic volume with 99mTc-tilmanocept uptake
Time frame: Baseline and 12 Months
Relationship between change in macrophage-specific arterial infiltration with PCSK9 inhibitors and change in immune cell subpopulations (cells/µL)
Time frame: Baseline and 12 Months
Relationship between change in macrophage-specific arterial infiltration with PCSK9 inhibitors and change in markers of immune activation/ systemic inflammation
Time frame: Baseline and 12 Months
Relationship between change in macrophage-specific arterial infiltration with PCSK9 inhibitors and baseline immune cell subpopulations (cells/µL)
Time frame: Baseline and 12 Months
Relationship between change in macrophage-specific arterial infiltration with PCSK9 inhibitors and baseline markers of immune activation/ systemic inflammation
Time frame: Baseline and 12 Months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2025.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Atherosclerotic Cardiovascular Disease and Cardiovascular Diseases, run by Massachusetts General Hospital 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 4 inclusion and 10 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: withdrawn, as of the sponsor's last update on 26 Sep 2025. 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.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Between-group difference (case participants versus control participants) in percent volume with aortic 99mTc-tilmanocept uptake across different uptake thresholds (time frame: Baseline). The study lists 2 primary outcomes in all. 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 Sep 2025.