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Effect of Sirolimus on Molecular Alterations in Cerebral Aneurysms

Primary Purpose

Cerebral Aneurysm

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Microsurgical clipping
Endovascular treatment
Sirolimus
Sponsored by
University of Miami
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Cerebral Aneurysm

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of MiamiRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Microsurgical Clipping Treated with Sirolimus

Endovascular Treatment Treated with Sirolimus

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.
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).
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.

Secondary Outcome Measures

Full Information

First Posted
October 24, 2019
Last Updated
August 11, 2023
Sponsor
University of Miami
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
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1. Study Identification

Unique Protocol Identification Number
NCT04141020
Brief Title
Effect of Sirolimus on Molecular Alterations in Cerebral Aneurysms
Official Title
Effect of Sirolimus on Molecular Alterations in Cerebral Aneurysms
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 27, 2021 (Actual)
Primary Completion Date
November 1, 2026 (Anticipated)
Study Completion Date
November 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Miami
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cerebral Aneurysm

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Non-Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Microsurgical Clipping Treated with Sirolimus
Arm Type
Experimental
Arm Description
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.
Arm Title
Endovascular Treatment Treated with Sirolimus
Arm Type
Experimental
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Microsurgical clipping
Intervention Description
Standard of care microsurgical clipping of an unruptured cerebral artery aneurysm.
Intervention Type
Procedure
Intervention Name(s)
Endovascular treatment
Intervention Description
Standard of care endovascular treatment of an unruptured cerebral artery aneurysm.
Intervention Type
Drug
Intervention Name(s)
Sirolimus
Other Intervention Name(s)
Rapamune
Intervention Description
Daily oral Sirolimus 2 mg tablets, adjusted as necessary per treating physician.
Primary Outcome Measure Information:
Title
Change in gene expression from control arteries.
Description
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.
Time Frame
Day 18
Title
Change in gene expression between blood samples.
Description
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).
Time Frame
Day 18
Title
Change in gene expression.
Description
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.
Time Frame
Day 18

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anabela M Cieslicki
Phone
305-243-8044
Email
axc1623@med.miami.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert M Starke, M.D.
Organizational Affiliation
University of Miami
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anabela M Cieslicki
Phone
305-243-8044
Email
axc1623@med.miami.edu
First Name & Middle Initial & Last Name & Degree
Robert M Starke, M.D.

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Effect of Sirolimus on Molecular Alterations in Cerebral Aneurysms

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