Effect of Sirolimus on Molecular Alterations in Cerebral Aneurysms

Phase 2

Recruiting

• Conditions: Cerebral Aneurysm
• Interventions: Procedure: Microsurgical clipping; Procedure: Endovascular treatment; Drug: Sirolimus

• Registration Number: NCT04141020
• Lead Sponsor: University of Miami

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-10-24
• Study First Submitted QC: 2019-10-24
• Study First Posted: 2019-10-28
• Study Start: 2021-10-27
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-14
• Last Update Posted: 2025-03-17
• Primary Completion: 2026-11-01
• Study Completion: 2026-11-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Microsurgical Clipping Treated with Sirolimus	Microsurgical clipping	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.
Microsurgical Clipping Treated with Sirolimus	Sirolimus	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.
Endovascular Treatment Treated with Sirolimus	Endovascular treatment	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.
Endovascular Treatment Treated with Sirolimus	Sirolimus	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.

Primary Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

University of Miami; 🇺🇸 Miami, Florida, United States