Effect of Sirolimus on Molecular Alterations in Cerebral Aneurysms

• Sponsor: University of Miami (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04141020
• Collaborator: National Institute of Neurological Disorders and Stroke (NINDS) (NIH)
• Enrollment: 80
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 60.2
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Cerebral Aneurysm	Procedure: Microsurgical clipping; Procedure: Endovascular treatment; Drug: Sirolimus	Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 80 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: Effect of Sirolimus on Molecular Alterations in Cerebral Aneurysms
• Actual Study Start Date: Oct 27, 2021
• Anticipated Primary Completion Date: Nov 1, 2026
• Anticipated Study Completion Date: Nov 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Microsurgical Clipping Treated with 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.	Procedure: Microsurgical clipping; Standard of care microsurgical clipping of an unruptured cerebral artery aneurysm.; Drug: Sirolimus; Daily oral Sirolimus 2 mg tablets, adjusted as necessary per treating physician.; Other Names: Rapamune
Experimental: Endovascular Treatment Treated with 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.	Procedure: 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.; Other Names: Rapamune

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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).

3. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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)

1. ≥ 18 years of age

2. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Miami	Miami	Florida	United States	33136

Sponsors and Collaborators

• University of Miami
• National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

• Principal Investigator: Robert M Starke, M.D., University of Miami

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Robert Starke, Assistant Professor, University of Miami
• ClinicalTrials.gov Identifier: NCT04141020
• Other Study ID Numbers: 20190857; 1R01NS111119-01A1
• First Posted: Oct 28, 2019
• Last Update Posted: Nov 1, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Intracranial Aneurysm; Aneurysm; Sirolimus

Study Results

No Results Posted as of Nov 1, 2021