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| ID | Type | Description | Link |
|---|---|---|---|
| R01HL166991 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
| Amgen | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Evolocumab | Experimental | 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). |
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| Placebo | Placebo Comparator | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Evolocumab | Drug | See arm description. |
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | AAA Repair (Week 5) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | AAA Repair (Week 5) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Scott Damrauer, MD | Contact | 215-615-1698 | damrauer@upenn.edu |
| Name | Affiliation | Role |
|---|---|---|
| Scott Damrauer, MD | University of Pennsylvania | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital of the University of Pennsylvania | Philadelphia | Pennsylvania | 19010 | United States |
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| ID | Term |
|---|---|
| D017544 | Aortic Aneurysm, Abdominal |
| ID | Term |
|---|---|
| D001014 | Aortic Aneurysm |
| D000783 | Aneurysm |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| C577155 | evolocumab |
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| Drug |
See arm description. |
|
| 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 |
| AAA Repair (Week 5) |
| 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 | AAA Repair (Week 5) |
| D001018 |
| Aortic Diseases |