Effect of Sirolimus on Molecular Alterations in Cerebral Aneurysms

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

Study Overview

• Status: Recruiting
• Conditions: Cerebral Aneurysm
• Intervention / Treatment: Procedure: Microsurgical clipping; Drug: Sirolimus; Procedure: Endovascular treatment

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Anabela M Cieslicki; Phone Number: 305-243-8044; Email: axc1623@med.miami.edu

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami
      • Contact: Anabela M Cieslicki; Phone Number: 305-243-8044; Email: axc1623@med.miami.edu
      • Principal Investigator: Robert M Starke, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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.	Drug: Sirolimus; Daily oral Sirolimus 2 mg tablets, adjusted as necessary per treating physician.; Other Names: Rapamune; Procedure: Endovascular treatment; Standard of care endovascular treatment of an unruptured cerebral artery aneurysm.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Miami
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Robert M Starke, M.D., University of Miami

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2021
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: October 24, 2019
• First Submitted That Met QC Criteria: October 24, 2019
• First Posted (Actual): October 28, 2019

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 11, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Arterial Diseases; Aneurysm; Intracranial Aneurysm; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: 20190857; 1R01NS111119-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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