Effect of Sirolimus on Molecular Alterations in Cerebral Aneurysms

Study Overview
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Brief Summary
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The objective of this study is to explore the effects of Sirolimus on the underlying molecular alterations of cerebral aneurysms.

Official Title
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Effect of Sirolimus on Molecular Alterations in Cerebral Aneurysms

Conditions
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Cerebral Aneurysm

Intervention / Treatment
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* Procedure: Microsurgical clipping
* Procedure: Endovascular treatment
* Drug: Sirolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Undergoing one of the following procedures at Jackson Memorial Hospital: Clipping of an unruptured cerebral artery aneurysm Endovascular treatment of unruptured cerebral aneurysms (including those receiving coiling) ≥ 18 years of age Willing and able to give informed consent Exclusion Criteria: 1) Subjects meeting any of the following criteria will be excluded: Dissecting, traumatic, or mycotic brain aneurysm. Women who are pregnant, or have a positive urine or blood (β-hCG) pregnancy test. Women who are breastfeeding. Any clinically significant psychiatric or psychological disease, which would preclude the patient from completing the protocol. Patients with known Human Immunodeficiency Virus (HIV) infection or other known immunodeficiency. Patient with renal or liver failure Interstitial pneumonitis History of lymphoma History of skin cancer Hypersensitivity to sirolimus Severe or unstable concomitant condition disease or chronic condition, which in the opinion of the investigator could affect assessment of the safety or efficacy of study intervention.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Microsurgical Clipping Treated with Sirolimus<br>Participants undergoing standard of care microsurgical clipping of unruptured cerebral aneurysm will be treated with 2 mg Sirolimus daily for 14-18 consecutive days prior to surgery. | Procedure: Microsurgical clipping<br>* Standard of care microsurgical clipping of an unruptured cerebral artery aneurysm.<br>Drug: Sirolimus<br>* Daily oral Sirolimus 2 mg tablets, adjusted as necessary per treating physician.<br>* Other names: Rapamune;|
| Experimental: Endovascular Treatment Treated with Sirolimus<br>Participants undergoing standard of care endovascular treatment of unruptured cerebral aneurysm procedure will be treated with 2 mg Sirolimus daily for 14-18 consecutive days prior to procedure. | Procedure: Endovascular treatment<br>* Standard of care endovascular treatment of an unruptured cerebral artery aneurysm.<br>Drug: Sirolimus<br>* Daily oral Sirolimus 2 mg tablets, adjusted as necessary per treating physician.<br>* Other names: Rapamune;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in gene expression from control arteries. | Change in gene expressions will be reported as fold change from control arteries: superficial temporal artery from the same patient and the intracerebral temporal lobe artery from a different patient. Genes to be evaluated are endothelial cell marker genes such as Cluster of Differentiation (CD) 34, CD31, Von Willebrand Factor (vWF), E-selectin, Vascular Endothelial (VE)-cadherin and Endothelial Nitric Oxide Synthase (eNOS) and pro-inflammatory-matrix remodeling proliferation genes such as Matrix Metallopeptidase (MMP)3 and MMP9, Vascular Cell Adhesion Molecule (VCAM)-1, Intercellular Adhesion Molecule (ICAM), Inducible Nitric Oxide Synthase (iNOS), Membrane Cofactor Protein (MCP) and Interleukin (IL)-1ß. | Day 18 | 
| Change in gene expression between blood samples. | Change in gene expressions will be reported as fold change of intra-aneurysmal blood to peripheral blood from the same patient. Genes to be evaluated are endothelial cell marker genes (CD34, CD31, vWF, E-selectin, VE-cadherin, and eNOS) and pro-inflammatory-matrix remodeling proliferation genes (MMP3, MMP9, VCAM-1, ICAM, iNOS, MCP, and IL-1ß). | Day 18 | 
| Change in gene expression. | Fold change of IL-2 expression and expression of endothelial cell marker genes (CD34, CD31, vWF, E-selectin, VE-cadherin, and eNOS) and pro-inflammatory-matrix remodeling proliferation genes (MMP3, MMP9, VCAM-1, ICAM, iNOS, MCP, and IL-1ß) will be evaluated between sirolimus treated to non-treated patients. | Day 18 |