WITHDRAWN

Immunomodulatory Effects of PCSK9 Inhibition

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

ImmuNomodulatory EffectS of PCSK9 Inhibition: A TaRgeted Molecular Imaging AppRoach

Quick Facts

Study Start:2024-04-04
Study Completion:2026-03
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:WITHDRAWN

Study ID

NCT05720156

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 85 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:Yes
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * 18 to 85 years of age
  2. * 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)
  3. * CASE PARTICIPANTS ONLY: High-intensity statin therapy for at least 6 months prior enrollment and without an interruption of \>1 month
  4. * CASE PARTICIPANTS ONLY: Initiation of PCSK9 inhibition with either evolocumab or alirocumab (and not inclisiran - PSCK9 inhibition through small interfering RNA)
  1. * pregnancy or breastfeeding
  2. * 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)
  3. * 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
  4. * use of oral steroids or prescription oral anti-inflammatory/immune suppressant medication for \> 7 days within the past 1 month
  5. * use of IV, IM or intra-articular steroids or IV, IM or intra-articular anti-inflammatory/immune suppressant medication within the past 3 months
  6. * Any prior use of PCSK9 inhibitors including both monoclonal antibodies or small interfering RNA
  7. * 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.
  8. * known allergy to dextrans and/or DTPA and/or radiometals
  9. * significant radiation exposure (\>2 CT angiograms) received within the past 12 months
  10. * concurrent enrollment in another research study judged by the study investigators to interfere with the current study

Contacts and Locations

Study Locations (Sites)

Massachusetts General Hospital
Boston, Massachusetts, 02114
United States

Collaborators and Investigators

Sponsor: Massachusetts General Hospital

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-04-04
Study Completion Date2026-03

Study Record Updates

Study Start Date2024-04-04
Study Completion Date2026-03

Terms related to this study

Additional Relevant MeSH Terms

  • Atherosclerotic Cardiovascular Disease
  • Cardiovascular Diseases
  • Atherosclerosis
  • Arterial Inflammation
  • Vascular Diseases
  • Vascular Disease, Peripheral
  • Vascular Calcification
  • High Cholesterol/Hyperlipidemia
  • Heart Diseases
  • Heart Attack
  • Stroke
  • Cerebrovascular Accident
  • Carotid Artery Diseases
  • Carotid Atherosclerosis
  • Transient Ischemic Attack