Cerebral Aneurysm
Conditions
Brief summary
The objective of this study is to explore the effects of Sirolimus on the underlying molecular alterations of cerebral aneurysms.
Interventions
PROCEDUREMicrosurgical clipping
Standard of care microsurgical clipping of an unruptured cerebral artery aneurysm.
PROCEDUREEndovascular treatment
Standard of care endovascular treatment of an unruptured cerebral artery aneurysm.
DRUGSirolimus
Daily oral Sirolimus 2 mg tablets, adjusted as necessary per treating physician.
Sponsors
University of Miami
National Institute of Neurological Disorders and Stroke (NINDS)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 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) 2. ≥ 18 years of age 3. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in gene expression from control arteries. | Day 18 | 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. |
| Change in gene expression between blood samples. | Day 18 | 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). |
| Change in gene expression. | Day 18 | 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. |
Countries
United States
Contacts
CONTACTJayro Toledo, MD
PRINCIPAL_INVESTIGATORRobert M Starke, M.D.
University of Miami
Outcome results
None listed