Effect of Sirolimus on Molecular Alterations in Cerebral Aneurysms

NCT04141020 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 201908571R01NS111119-01A1
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Cerebral Aneurysm

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (2)

Microsurgical Clipping Treated with Sirolimus

EXPERIMENTAL

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; Drug: Sirolimus

Endovascular Treatment Treated with Sirolimus

EXPERIMENTAL

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; Drug: Sirolimus

Interventions

Microsurgical clipping PROCEDURE

Standard of care microsurgical clipping of an unruptured cerebral artery aneurysm.

Microsurgical Clipping Treated with Sirolimus

Endovascular treatment PROCEDURE

Standard of care endovascular treatment of an unruptured cerebral artery aneurysm.

Endovascular Treatment Treated with Sirolimus

Sirolimus DRUG

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

Also known as: Rapamune

Endovascular Treatment Treated with Sirolimus; Microsurgical Clipping Treated with Sirolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• ≥ 18 years of age
• Willing and able to give informed consent

You may not qualify if:

• \) 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.

Sponsors & Collaborators

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

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

RECRUITING

MeSH Terms

Conditions

Intracranial Aneurysm

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Intracranial Arterial Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Aneurysm; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Robert M Starke, M.D.

  University of Miami

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jayro Toledo, MD

CONTACT

305-243-8044; j.toledo2@med.miami.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: October 24, 2019
• First Posted: October 28, 2019
• Study Start: October 27, 2021
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)