Liquid Biopsy Following BBB Disruption Using Barrier Disrupting Fields in Patients Undergoing Spine Surgery

NCT07224451 | Recruiting FDA Device

• 1 other identifier: SHEBA - 25 - 2323 - RH - CTIL
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Objective: To identify new central nervous system (CNS) biomarkers to be used for blood-derived liquid biopsy once the blood-brain barrier (BBB), specifically the blood-arachnoid barrier (BAB), has been transiently disrupted by BDF in patients undergoing spine surgery. Design: Single center (Sheba Medical Center), prospective, controlled. Phase: Feasibility study Endpoints: Efficacy The primary endpoint of the study is the elevation in blood concentration of CNS biomarkers following the study procedure compared to biomarkers detected in cerebrospinal fluid (CSF) of the same subject. Safety The primary safety endpoint will be the overall incidence of BDF procedure-related AEs and SAEs, with severity graded according to CTCAE v5.0 criteria. Study population: The study population will include up to 20 patients undergoing spine surgery. Study period: 24 months. Inclusion criteria:

1. 1.Adult subjects over the age of 18
2. 2.Able to sign informed consent
3. 3.Candidates for intradural tumor resection spinal surgery with intraoperative neuromonitoring.
4. 4.Pacemakers, or other implanted electric medical devices
5. 5.Pregnant or lactating females
6. 6.Major medical, neurologic or psychiatric condition who are judged as unable to fully comply with the study
7. 7.History of skull fractures or previous brain surgery
8. 8.American Society of Anesthesiologists grade \>2
9. 9.Anticoagulants treatment
10. 10.Damage to the dura resulting in CSF leak
11. 11.Patients with seizures/epilepsy
12. 12.Candidates for intradural tumor resection spinal surgery with intraoperative neuromonitoring will be enrolled in the study prior to surgery.
13. 13.The patient will undergo preparation for surgery according to the standard care.
14. 14.Once anesthetized and intubated, electrodes will be attached to the patient's head.
15. 15.After placing the electrodes, when the patient is under anesthesia, a blood sample will be taken prior to BDF. This sample will be used as baseline for BDF.
16. 16.The patient will then undergo a BDF procedure.
17. 17.Additional blood samples will be taken for identification of CNS biomarkers.
18. 18.Surgery will then proceed according to the standard of care.
19. 19.Once the dura is opened, a CSF sample will be taken, in order to compare the blood biomarkers of the specific subject with the CSF biomarkers.
20. 20.The surgery will continue according to the standard of care.

Conditions

Spinal Tumors

Keywords

Barrier disrupting fields; pulse electrical fields; blood-brain barrier opening; blood-arachnoid barrier opening; liquid biopsy; spinal tumors

Outcome Measures

Primary Outcomes (1)

• Elevation in blood concentration of CNS biomarkers following BDF compared to biomarkers detected in CSF of the same subject. The overall incidence of BDF procedure-related AEs and SAEs, with severity graded according to CTCAE v5.0 criteria.

  Efficacy We will quantify potential biomarkers in pre- and post- BDF blood samples and expect to see an increase in the blood concentration in the post-BDF samples. The primary endpoint of the study is the elevation in blood concentration of CNS biomarkers including fatty acid or other lipid levels, and/or barrier opening biomarkers and/or unique vascular and cytokines-related proteins and metabolites, following BDF, compared to biomarkers detected in cerebrospinal fluid (CSF) of the same subject. Safety The primary safety endpoint will be the overall incidence of BDF procedure-related AEs and SAEs, with severity graded according to CTCAE v5.0 criteria.

  Blood samples will be acquired before and 5 and 10 min post BDF. Another blood sample will be taken before opening the dura. CSF sample will be taken at the time of opening the dura.

Study Arms (1)

BDF are applied following anaesthesia, blood/CSF samples acquired

EXPERIMENTAL

Following anaesthesia a blood sample will be acquired, followed by BDF, following by additional blood samples acquisition and finally a CSF sample when opening the dura

Procedure: spinal surgery; Device: BDF

Interventions

spinal surgery PROCEDURE

Candidates for intradural tumor resection spinal surgery with intraoperative neuromonitoring will be enrolled in the study prior to surgery. The patient will undergo preparation for surgery according to the standard care. Once anesthetized and intubated, electrodes will be attached to the patient's head. After placing the electrodes, when the patient is under anesthesia, a blood sample will be taken prior to BDF. This sample will be used as baseline for BDF. The patient will then undergo a BDF procedure. Additional blood samples will be taken for identification of CNS biomarkers. Surgery will then proceed according to the standard of care. Once the dura is opened, a CSF sample will be taken. The surgery will continue according to the standard of care

Also known as: Barrier disrupting fields, Acquire blood samples, Acquire CSF sample

BDF are applied following anaesthesia, blood/CSF samples acquired

BDF DEVICE

electrodes couples (voltage and ground) will be placed on the patient head and will be connected to a pulse generator. 2 electrodes couples will be activated in parallel, up to 8 electrodes couples total. EEG will be acquired after each series of pulses for a few sec.

Also known as: pulsed electric fields

BDF are applied following anaesthesia, blood/CSF samples acquired

Eligibility Criteria

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

You may qualify if:

• Adult subjects over the age of 18
• Able to sign informed consent
• Candidates for intradural tumor resection spinal surgery with intraoperative neuromonitoring.

You may not qualify if:

• Pacemakers, or other implanted electric medical devices
• Pregnant or lactating females
• Major medical, neurologic or psychiatric condition who are judged as unable to fully comply with the study
• History of skull fractures or previous brain surgery
• American Society of Anesthesiologists grade \>2
• Anticoagulants treatment
• Damage to the dura resulting in CSF leak
• Patients with seizures/epilepsy

Sponsors & Collaborators

• Sheba Medical Center: lead

Study Sites (1)

Sheba Medical Center

Ramat Gan, 52621, Israel

RECRUITING

Related Publications (2)

• Sharabi S, Last D, Daniels D, Fabian ID, Atrakchi D, Bresler Y, Liraz-Zaltsman S, Cooper I, Mardor Y. Non-Invasive Low Pulsed Electrical Fields for Inducing BBB Disruption in Mice-Feasibility Demonstration. Pharmaceutics. 2021 Jan 27;13(2):169. doi: 10.3390/pharmaceutics13020169.

  PMID: 33513968 RESULT

• Sharabi S, Bresler Y, Ravid O, Shemesh C, Atrakchi D, Schnaider-Beeri M, Gosselet F, Dehouck L, Last D, Guez D, Daniels D, Mardor Y, Cooper I. Transient blood-brain barrier disruption is induced by low pulsed electrical fields in vitro: an analysis of permeability and trans-endothelial electric resistivity. Drug Deliv. 2019 Dec;26(1):459-469. doi: 10.1080/10717544.2019.1571123.

  PMID: 30957567 RESULT

Related Links

• Israeli ministry of health list of clinical trials

MeSH Terms

Conditions

Spinal Cord Neoplasms

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Ran Harel, MD

  Sheba Medical Center

  PRINCIPAL INVESTIGATOR

• Yael Mardor, PhD

  Sheba Medical Center

  STUDY CHAIR

Central Study Contacts

Yael Mardor, PhD

CONTACT

+97235302993; yael.mardor@sheba.health.gov.il, yael.mardor@gmail.com

Ran Harel, MD

CONTACT

+97235302440; ran.harel@sheba.health.gov.il

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: The subcontractor laboratories assessing the blood and CSF samples will be blinded
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Spine Surgery Division, Department of Neurosurgery Sheba Medical Center, Israel

Study Record Dates

• First Submitted: November 3, 2025
• First Posted: November 4, 2025
• Study Start: October 16, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: November 4, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 9 months and ending 36 months following article publication
• Access Criteria: Researchers who provide a methodologically sound proposal will receive the de-identified individual participant data that underlie the results reported in a published article (text, tables, figures, and appendices) by mail upon providing a methodologically sound proposal

Locations

IL (1)