Effect of Sirolimus on Molecular Alterations in Cerebral Aneurysms

Cerebral Aneurysm Clinical Trial

Official title:

Effect of Sirolimus on Molecular Alterations in Cerebral Aneurysms

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04141020
• Other study ID #: 20190857
• Secondary ID: 1R01NS111119-01A
• Status: Recruiting
• Phase: Phase 2
• Start date: October 27, 2021
• Est. completion date: November 1, 2026

Study information

• Verified date: August 2023
• Source: University of Miami
• Contact: Anabela M Cieslicki
• Phone: 305-243-8044
• Email: axc1623[@]med.miami.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: November 1, 2026
• Est. primary completion date: November 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (ß-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.

Related Conditions & MeSH terms

• Aneurysm
• Cerebral Aneurysm
• Intracranial Aneurysm

Intervention

Procedure:
• Microsurgical clipping
Standard of care microsurgical clipping of an unruptured cerebral artery aneurysm.
• Endovascular treatment
Standard of care endovascular treatment of an unruptured cerebral artery aneurysm.

Drug:
• Sirolimus
Daily oral Sirolimus 2 mg tablets, adjusted as necessary per treating physician.

Locations

Country	Name	City	State
United States	University of Miami	Miami	Florida

Sponsors (2)

Lead Sponsor	Collaborator
University of Miami	National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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