Back to resultsMechanistic Clinical Trial of PCSK9 Inhibition for AAA
Primary Purpose
Abdominal Aortic Aneurysm
Status
Not yet recruiting
Phase
Early Phase 1
Locations
Study Type
Interventional
Intervention
Evolocumab
Placebo
Sponsored by
About this trial
This is an interventional other trial for Abdominal Aortic Aneurysm
Eligibility Criteria
Inclusion Criteria: Abdominal aortic aneurysm (AAA) requiring open surgical repair Age > 18 Provision of signed and dated informed consent form Stated willingness to comply with all study procedures and availability for the duration of the study Exclusion Criteria: Prior use of a PCSK9 inhibitor (evolocumab, alirocumab, inclisiran) within 6 months of the baseline visit LDL-C < 40 mg/dL (within 3 months of baseline visit) Known allergy to PCSK9 inhibitor Aortic dissection Vascular connective tissue disorders Type I-III or V Thoraco-abdominal Aortic Aneurysm Vasculitis or inflammatory aneurysm Pregnant or lactating women Poorly controlled diabetes (A1C > 10%) Chronic kidney disease Stage 4/5 or End Stage Renal Disease (ESRD) on hemodialysis (HD) Liver Disease (alanine transaminase [ALT] or aspartate aminotransferase [ALT] > 3.0 x upper limits of normal) (within 3 months of baseline visit) Known latex or naturally rubber allergy Treatment with another investigational product within 30 days or 5 half-lives of the investigation drug before consent (whichever is longer) that would have an impact on endpoints associated with this trial. Any other condition that the Investigator feels prohibits participants' ability to comply with study or follow up.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Evolocumab
Placebo
Arm Description
Evolocumab is the drug that will be administered in this study. It will be administered as a 140mg subcutaneous injection every 14 days for 5 weeks (for a total of 3 doses).
This arm is a matching placebo that will be administered in the same fashion as the study drug if the patient is randomized to placebo.
Outcomes
Primary Outcome Measures
Interleukin (IL)-6 in myeloid derived monocytes/macrophages from in AAA tissue
IL-6 expression will be measured in myeloid cells in the aortic tissue specimens using single nucleus RNA sequencing and confirmed by whole tissue ELISA.
Secondary Outcome Measures
Matrix metalloproteinase (MMP)-9 in myeloid derived monocytes/macrophages from in AAA tissue
MMP-9 expression will be measured in myeloid cells in the aortic tissue specimens using single nucleus RNA sequencing and confirmed by whole tissue ELISA and immunofluorescence activity assays.
Infiltrating immune cell composition and their activation/inflammatory states in AAA tissue
Relative numbers of infiltrating immune cell type and their activation/inflammatory state as measured by a combination of bulk and single nuclear RNA sequencing
Smooth muscle composition of AAA tissue
The relative numbers of smooth muscle cells and their contractile/proliferative state as measured by a combination of bulk and single nucleus RNA sequencing
Full Information
NCT ID
NCT06081153
First Posted
October 3, 2023
Last Updated
October 12, 2023
Sponsor
University of Pennsylvania
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), Amgen
1. Study Identification
Unique Protocol Identification Number
NCT06081153
Brief Title
Mechanistic Clinical Trial of PCSK9 Inhibition for AAA
Official Title
A Randomized, Placebo-Controlled Mechanistic Clinical Trial of PCSK9 Inhibition With Evolocumab in Patients Undergoing Open Abdominal Aortic Aneurysm Repair
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 1, 2023 (Anticipated)
Primary Completion Date
November 1, 2028 (Anticipated)
Study Completion Date
November 1, 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Pennsylvania
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), Amgen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
5. Study Description
Brief Summary
The goal of this mechanistic clinical trial is to assess whether lowering the low-density lipoprotein cholesterol (LDL-C) levels in the blood with the injections of the medication evolocumab will have any effect on the tissue or cells of patients with abdominal aortic aneurysm (AAA). Researchers will compare participants receiving evolocumab injections to participants receiving placebo injections to see how the tissue and cells of the aorta are affected by changes in LDL-C levels.
Detailed Description
After being informed about the study and its potential risks, all patients giving informed consent will undergo a baseline visit and be randomized to received either evolocumab 140mg subcutaneously or placebo. This baseline visit includes a vital signs assessment, laboratory tests, medical history and medication review, a pregnancy test (if applicable), and training on how to perform drug injections. Participants will receive 3 doses/autoinjectors of study drug or placebo and be instructed to perform injections every 14 days starting 5 weeks prior to their scheduled AAA repair. If the baseline assessment occurs 5 weeks prior to their scheduled AAA, the first injection will be performed during this visit. Participants will have the option of coming back to the site for injections 2 and 3 or perform these injections at home under telehealth supervision. At the time of open AAA repair, participants will repeat laboratory tests and have a sample of aneurysm tissue taken. Participants will then have a follow up phone call 4 weeks after AAA repair to assess for any adverse events. At the conclusion of the study investigators will examine gene expression and protein levels in the aortic tissue to determine the impact of LDL-C lowering with evolocumab.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Abdominal Aortic Aneurysm
7. Study Design
Primary Purpose
Other
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
44 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Evolocumab
Arm Type
Experimental
Arm Description
Evolocumab is the drug that will be administered in this study. It will be administered as a 140mg subcutaneous injection every 14 days for 5 weeks (for a total of 3 doses).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
This arm is a matching placebo that will be administered in the same fashion as the study drug if the patient is randomized to placebo.
Intervention Type
Drug
Intervention Name(s)
Evolocumab
Intervention Description
See arm description.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
See arm description.
Primary Outcome Measure Information:
Title
Interleukin (IL)-6 in myeloid derived monocytes/macrophages from in AAA tissue
Description
IL-6 expression will be measured in myeloid cells in the aortic tissue specimens using single nucleus RNA sequencing and confirmed by whole tissue ELISA.
Time Frame
AAA Repair (Week 5)
Secondary Outcome Measure Information:
Title
Matrix metalloproteinase (MMP)-9 in myeloid derived monocytes/macrophages from in AAA tissue
Description
MMP-9 expression will be measured in myeloid cells in the aortic tissue specimens using single nucleus RNA sequencing and confirmed by whole tissue ELISA and immunofluorescence activity assays.
Time Frame
AAA Repair (Week 5)
Title
Infiltrating immune cell composition and their activation/inflammatory states in AAA tissue
Description
Relative numbers of infiltrating immune cell type and their activation/inflammatory state as measured by a combination of bulk and single nuclear RNA sequencing
Time Frame
AAA Repair (Week 5)
Title
Smooth muscle composition of AAA tissue
Description
The relative numbers of smooth muscle cells and their contractile/proliferative state as measured by a combination of bulk and single nucleus RNA sequencing
Time Frame
AAA Repair (Week 5)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Abdominal aortic aneurysm (AAA) requiring open surgical repair
Age > 18
Provision of signed and dated informed consent form
Stated willingness to comply with all study procedures and availability for the duration of the study
Exclusion Criteria:
Prior use of a PCSK9 inhibitor (evolocumab, alirocumab, inclisiran) within 6 months of the baseline visit
LDL-C < 40 mg/dL (within 3 months of baseline visit)
Known allergy to PCSK9 inhibitor
Aortic dissection
Vascular connective tissue disorders
Type I-III or V Thoraco-abdominal Aortic Aneurysm
Vasculitis or inflammatory aneurysm
Pregnant or lactating women
Poorly controlled diabetes (A1C > 10%)
Chronic kidney disease Stage 4/5 or End Stage Renal Disease (ESRD) on hemodialysis (HD)
Liver Disease (alanine transaminase [ALT] or aspartate aminotransferase [ALT] > 3.0 x upper limits of normal) (within 3 months of baseline visit)
Known latex or naturally rubber allergy
Treatment with another investigational product within 30 days or 5 half-lives of the investigation drug before consent (whichever is longer) that would have an impact on endpoints associated with this trial.
Any other condition that the Investigator feels prohibits participants' ability to comply with study or follow up.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kevin Dougherty, MPH
Phone
215-662-2243
Email
kevin.dougherty@pennmedicine.upenn.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Tiffany Sharkoski, MPH
Phone
215-615-2354
Email
sharkosk@pennmedicine.upenn.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Scott Damrauer, MD
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
Mechanistic Clinical Trial of PCSK9 Inhibition for AAA
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