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

NCT ID: NCT07224451

Last Updated: 2025-11-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-10-16

Study Completion Date

2027-10-31

Brief Summary

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

Exclusion criteria:

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

Study procedure:

1. Candidates for intradural tumor resection spinal surgery with intraoperative neuromonitoring will be enrolled in the study prior to surgery.
2. The patient will undergo preparation for surgery according to the standard care.
3. Once anesthetized and intubated, electrodes will be attached to the patient's head.
4. 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.
5. The patient will then undergo a BDF procedure.
6. Additional blood samples will be taken for identification of CNS biomarkers.
7. Surgery will then proceed according to the standard of care.
8. 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.
9. The surgery will continue according to the standard of care.

Detailed Description

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Barrier-disrupting fields (BDF), based on low pulsed electric fields, offer a non-invasive and transient method for selectively opening CNS barriers. We have previously shown that BDF can be applied for efficient delivery of systemically administered drugs into the CNS in rodents. We further demonstrated the application of BDF to enable blood-based detection of brain-derived proteins in rats and mice.

The primary endpoint of the study is the elevation in blood concentration of CNS biomarkers following the study procedure compared to biomarkers detected in CSF of the same subject. The concentration of the biomarkers is expected to be elevated in the blood after the BDF procedure. These include specific CSF proteins such as Protein S100A, S100B and prostaglandin D2 isomerase and include additional proteins identified by us in preclinical experiments in rats, and other CNS-derived molecules that were not identified in our preliminary studies.

Candidates for intradural tumor resection spinal surgery with intraoperative neuromonitoring will be enrolled in the study prior to surgery.

BDF treatment parameters are planned using a simulation package. The distributions of electric fields on the BAB are calculated using a finite elements model, to reach desired electric fields on the BAB needed for inducing BAB disruption. This is done using a simulation package, based on brain MRI after tissue segmentation. Different locations, sizes and distances between the electrodes are modeled in order to reach the optimal setup for obtaining optimal BAB disruption with no BBB disruption.

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 post BDF 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. Adverse Events will be recorded according to CTCAE V 5.

Conditions

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Spinal Tumors

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

The subcontractor laboratories assessing the blood and CSF samples will be blinded

Study Groups

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BDF are applied following anaesthesia, blood/CSF samples acquired

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

Group Type EXPERIMENTAL

spinal surgery

Intervention Type 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

BDF

Intervention Type 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.

Interventions

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spinal surgery

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

Intervention Type PROCEDURE

BDF

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.

Intervention Type DEVICE

Other Intervention Names

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Barrier disrupting fields Acquire blood samples Acquire CSF sample pulsed electric fields

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sheba Medical Center

OTHER_GOV

Sponsor Role lead

Responsible Party

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Ran Harel

Director of Spine Surgery Division, Department of Neurosurgery Sheba Medical Center, Israel

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ran Harel, MD

Role: PRINCIPAL_INVESTIGATOR

Sheba Medical Center

Yael Mardor, PhD

Role: STUDY_CHAIR

Sheba Medical Center

Locations

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Sheba Medical Center

Ramat Gan, , Israel

Site Status RECRUITING

Countries

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Israel

Central Contacts

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Yael Mardor, PhD

Role: CONTACT

Ran Harel, MD

Role: CONTACT

+97235302440

Facility Contacts

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Yael Mardor, PhD

Role: primary

Ran Harel, MD

Role: backup

+97235302440

References

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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.

Reference Type RESULT
PMID: 33513968 (View on PubMed)

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.

Reference Type RESULT
PMID: 30957567 (View on PubMed)

Related Links

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Other Identifiers

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SHEBA - 25 - 2323 - RH - CTIL

Identifier Type: -

Identifier Source: org_study_id

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