Spinal TumorsBDF002NCT07224451
Liquid Biopsy Following BBB Disruption Using Barrier Disrupting Fields in Patients Undergoing Spine Surgery
A study testing spinal surgery and BDF in people with Spinal Tumors, run by Sheba Medical Center at 1 site in Israel.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Spinal Tumors
- What is being tested?
- spinal surgery and BDF
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteIsrael
- Study dates
- 16 Oct 2025to Oct 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult subjects over the age of 18
- Able to sign informed consent
- Candidates for intradural tumor resection spinal surgery with intraoperative neuromonitoring.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Israel1 site, 1 recruiting
- Recruiting
Sheba Medical Center
Ramat Gan, 52621
Yael Mardor, PhD, +97235302993, yael.mardor@sheba.health.gov.il, yael.mardor@gmail.com
Ran Harel, MD, +97235302440, ran.harel@sheba.health.gov.il
About this study
Official title: Liquid Biopsy Following Blood-Brain Barrier Disruption Using Barrier Disrupting Fields in Patients Undergoing Spine Surgery
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
Read more
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:
- 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
Study 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, in order to compare the blood biomarkers of the specific subject with the CSF biomarkers.
- The surgery will continue according to the standard of care.
Read the detailed description
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
- Spinal Tumors
- Being tested
- spinal surgery, BDF
- Keywords
- Barrier disrupting fields, pulse electrical fields, blood-brain barrier opening, blood-arachnoid barrier opening, liquid biopsy, spinal tumors
- Medical subject headings
- Spinal Cord Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
spinal surgeryProcedure or surgery
Also called Barrier disrupting fields, Acquire blood samples, Acquire CSF sample
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
BDFDevice
Also called pulsed electric fields
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Procedure: spinal surgery; Device: BDF |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2025
- Study start16 Oct 2025
- Primary completionOct 2027 (estimated)
- Study completionOct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Spinal TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sheba Medical Center
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Ran Harel, Sheba Medical Center
- Investigators
- Ran Harel, MD, Principal investigator, Sheba Medical CenterYael Mardor, PhD, Study chair, Sheba Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07224451
- Sponsor's protocol ID
- SHEBA - 25 - 2323 - RH - CTIL
- Acronym
- BDF002
- Status last verified
- Oct 2025
- First submitted
- 3 Nov 2025
- Last updated
- 4 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: De-identified individual participant data that underlie the results reported in a published article (text, tables, figures, and appendices) will be available to qualified researchers upon reasonable request.
Publications
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.
PubMed 33513968Sharabi 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.
PubMed 30957567
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Liquid Biopsy Following Blood-Brain Barrier Disruption Using Barrier Disrupting Fields in Patients Undergoing Spine Surgery
- ClinicalTrials.gov ID
- NCT07224451
- Acronym / sponsor ID
- BDF002 / SHEBA - 25 - 2323 - RH - CTIL
- Conditions
- Spinal Tumors
- Keywords
- Barrier disrupting fields, pulse electrical fields, blood-brain barrier opening, blood-arachnoid barrier opening, liquid biopsy, spinal tumors
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Sheba Medical CenterOther government
- Study start
- 16 Oct 2025 (actual)
- Primary completion
- Oct 2027 (estimated)
- Study completion
- Oct 2027 (estimated)
- First posted
- 4 Nov 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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
Study 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, in order to compare the blood biomarkers of the specific subject with the CSF biomarkers.
- The surgery will continue according to the standard of care.
Detailed description
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BDF are applied following anaesthesia, blood/CSF samples acquired | Experimental | Procedure: spinal surgery, Device: BDFFollowing 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Adult subjects over the age of 18
- Able to sign informed consent
- Candidates for intradural tumor resection spinal surgery with intraoperative neuromonitoring.
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| spinal surgeryAlso: Barrier disrupting fields, Acquire blood samples, Acquire CSF sampleCandidates 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 | Procedure or surgery | BDF are applied following anaesthesia, blood/CSF samples acquired |
| BDFAlso: pulsed electric fieldselectrodes 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. | Device | BDF are applied following anaesthesia, blood/CSF samples acquired |
Primary outcome
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.
Time frame: 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.
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2025.
- Results publication: PubMed 33513968Sharabi 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.
- Results publication: PubMed 30957567Sharabi 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.
- Israeli ministry of health list of clinical trialsLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual participant data that underlie the results reported in a published article (text, tables, figures, and appendices) will be available to qualified researchers upon reasonable request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ran Harel, MD principal investigator
Sheba Medical Center
Yael Mardor, PhD study chair
Sheba Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing spinal surgery and BDF in people with Spinal Tumors, run by Sheba Medical Center at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yael Mardor, PhD (+97235302993, yael.mardor@sheba.health.gov.il, yael.mardor@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07224451, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2025.