GliomaNCT04745156
A Study Using Brain Stimulation and Behavioral Therapy to Increase Extent of Resection in Low-Grade Gliomas
A study testing RNS System Implantation in people with Glioma and Glioma Intracranial, run by Medical College of Wisconsin.
Trial summary
This study uses a cranial implant to deliver cortical stimulation that, when paired with physiotherapy, will remap the brain so that critical brain functions can be protected during brain tumor surgery. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Glioma, Glioma Intracranial, Gliomas Benign
- What is being tested?
- RNS System Implantation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- No sites listed yet
- Study dates
- 1 Aug 2028to Sep 2033
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-65 years old
- Ability to understand a written informed consent document, and the willingness to sign it
- Radiographic evidence of likely low-grade glioma on MRI (i.e. non-enhancing) invading primary motor cortex in the non-dominant hemisphere.
- Karnofsky performance status (KPS) ≥ 75
- Normal or near normal motor strength (i.e., at least 3/5 in relevant areas)
- Normal or near normal speech (Can consistently name at least 4/5 cards)
- No medical contraindication to surgery
- Free of other illness that may shorten life expectancy
Who cannot join
- Presence of other malignancy not in remission
- Evidence of bi-hemispheric or widespread tumor involvement
- Likely candidate to receive GTR on initial resection
- Medically high-risk surgical candidate
- History of recent scalp or systemic infection
- Presence of other implants or foreign bodies in the head
Show all 15Show fewer
- Inability to receive an MRI for any reason
- Inability to receive cortical stimulation for any reason
- Coagulation disorders and/or use of anti-thrombotic therapies
- Platelet count < 50
- Diathermy procedures
- Electroconvulsive Therapy (ECT)
- Transcranial Magnetic Stimulation (TMS)
- Presence of implanted cardiac device (such as a pacemaker or defibrillator)
- Pregnant women
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Inducing Functional Plasticity in Glioma-Involved Functional Cortex With Deficit-Inducing Cortical Stimulation and Targeted Behavioral Therapy to Increase Extent of Resection
This study uses a cranial implant to deliver cortical stimulation that, when paired with physiotherapy, will remap the brain so that critical brain functions can be protected during brain tumor surgery. This pilot study will provide initial evidence for the safety and feasibility of such a protocol which will lead to future pivotal trials that could radically change eloquent area brain surgery. For patients with otherwise incompletely resectable brain tumors, this could mean a longer life expectancy and a better quality of life.
Read the detailed description
Study Protocol: Participants will undergo a standard-of-care craniotomy for resection of low-grade glioma. If part of the lesion cannot be removed due to involvement of functional cortex, RNS (Responsive Neurostimulation System [RNS; NeuroPace, Inc.]) electrodes will be implanted over the tumor-invaded area(s) in five participants. Stimulation will then be optimized for each individual to disrupt the function of the invaded cortical node (e.g., hand motor area -> hand dysfunction) (Aim 1). Over the next two months, outpatient physiotherapy will work to overcome the stim-induced deficits through gradual increases in stimulation amplitude as other, non-stimulated brain regions begin to assume its function (Aim 2). Once complete, participants will return to the OR for device explantation, repeated intraoperative mapping, and extended resection (if safe) (Aim 3).
Aim 1: Optimize stimulation to maximize stim-induced deficits and minimize side effects Rationale: To induce plasticity, stimulation parameters must be individually tuned to maximize effect and minimize side effects. Approach: After device implantation and prior to hospital discharge, stimulus settings (frequency, pulse-width, and amplitude) will be optimized to the relevant clinical response while minimizing adverse effects (e.g., focal tonus, myoclonus, or seizures) while still in the safe, inpatient setting. Outcomes: Primary Endpoints: 1) stim-induced focal clinical deficit as measured on the relevant clinical scale (e.g., manual motor score [0-5], picture naming [x/10]), repetition [x/3]); 2) stim-induced side effects (e.g., seizures).
Aim 2: Evaluate extent of remapping and safety of outpatient stimulation-physiotherapy protocol. Rationale: The ability to deliver chronic, outpatient stimulation is vital for practical clinical translation, yet neither its safety nor efficacy has been demonstrated. Approach: After Aim 1, a physiotherapist will assign a personalized, outpatient therapy regimen aimed at overcoming stim-induced deficits. Participants will have daily virtual sessions and return to clinic 2x/week for amplitude increases to re-induce deficits that therapy has overcome. This will continue until stimulation no longer can induce a deficit, suggesting successful functional remapping and enabling a return to the OR for further resection. Outcomes: Primary Endpoints: 1) absence of stim-related ER visits, readmissions, or serious adverse events (safety), 2) changes in intraop stimulation maps from surgery 1 to surgery 2 (induced remapping).
Aim 3: Evaluate ability to extend surgical resections and associated neurological outcomes. Rationale: Any change in functional boundaries will only be useful if it results in a safe, extended resection. Approach: Each surgery will proceed with standard-of-care intraoperative functional mapping techniques and decision making. Neurological examinations will be performed preoperatively, daily while inpatient, then again at 2-weeks and 3-months postoperatively. Extent of resection will be evaluated as 3D residual tumor volume on postoperative MRI. Outcomes: Primary Endpoint: 1) Change in residual tumor volume after second versus first resection, 2) new neurological deficits 3-months after second resection compared to before second resection. Secondary Endpoint: 1) New, temporary neurological deficits after the second surgery
- Conditions
- Glioma, Glioma Intracranial, Gliomas Benign, Brain Tumor, Brain Cancer, Motor Cortex; Lesion
- Being tested
- RNS System Implantation
- Keywords
- Brain Stimulation, NeuroPace, Cortex Stimulation, Neuroplasticity, Plasticity, Hand Motor Cortex, Primary Motor Cortex, M1, Motor Mapping, Resection, Surgery, Motor Rehabilitation, Prehabilitation
- Medical subject headings
- Glioma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RNS System ImplantationDevice
Following resection consistent with SoC, if there is evidence of residual tumor which cannot be resected due to invasion of hand-M1 but which is small enough to be covered by two four-electrode strips, these strips will be placed on the functional cortex of interest and secured to the dura. The location of the leads will be registered into the navigation software (either Medtronic Stealth or Brainlab). The dura will then be closed as watertight as possible, and the RNS System will be incorporated into the craniotomy on closure Prior to closure, four bone screws will be placed and registered to the intraoperative navigation system as internal fiducials to be retrieved for future procedures.
| Study group | Role | What they receive |
|---|---|---|
| RNS System Implantation | Experimental | This is a device feasibility study, therefore participants will only be enrolled into the investigational arm and will receive the RNS System Implantation. Receives: Device: RNS System Implantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Extent of resection
Calculated as: Tumor volume after second surgery - tumor volume before second surgery. Determination of volumes will be made by an attending radiologist without knowledge of clinical outcome. Manual segmentation will be performed to measure tumor volumes based on fluid-attenuated inversion recovery (FLAIR) axial slices.
Measured: Within 1 week after second surgery
Stimulation-induced motor deficits
Calculated as manual muscle score (MMS) before stimulation - MMS after stimulation.
MMS is a zero-to-five scale assessed as the following:
5 - normal strength 4 - give away weakness 3 - movement against gravity 2 - movement in anti-gravity position
1 - muscle twitch 0 - no movement
Measured: Within 2 weeks after first surgery
Stimulation-induced language deficits
3a. Calculated as picture naming score (x/10) before stimulation minus after stimulation.
3b. Calculated as sentence repitition score (x/3) before stimulation minus after stimulation.
Measured: Within 2 weeks after first surgery
Stimulation-induced side effects
Reported as number of unintended stimulation effects, such as myoclonus, tonus, seizures, or unpleasant sensations
Measured: Within 2 weeks after first surgery
Safety of outpatient stimulation-therapy protocol
Reported as number of stimulation- or physiotherapy related ER visits, readmissions, or serious adverse events
Measured: Up to 8 weeks
Stimulation-induced brain remapping
This outcome will be reported as a descriptive variable, calculated as changes in the intraoperative stimulation map obtained during surgery 2 compared to surgery 1
Measured: This data will be obtained intraoperatively during the second surgery
Number of participants with a new neurological deficit
Any new, permanent neurological deficits resulting from the second surgery
Measured: Assessed at 3-month postoperative visit after second surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2021
- Study start1 Aug 2028 (estimated)
- Primary completionAug 2033 (estimated)
- Study completionSep 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GliomaStudies 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
- Device feasibility
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Max Krucoff, MD, Medical College of Wisconsin
- Investigators
- Max Krucoff, MD, Principal investigator, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04745156
- Sponsor's protocol ID
- PRO00039766
- Status last verified
- Oct 2026
- First submitted
- 2 Feb 2021
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inducing Functional Plasticity in Glioma-Involved Functional Cortex With Deficit-Inducing Cortical Stimulation and Targeted Behavioral Therapy to Increase Extent of Resection
- ClinicalTrials.gov ID
- NCT04745156
- Acronym / sponsor ID
- PRO00039766
- Conditions
- Glioma, Glioma Intracranial, Gliomas Benign, Brain Tumor, Brain Cancer, Motor Cortex; Lesion
- Keywords
- Brain Stimulation, NeuroPace, Cortex Stimulation, Neuroplasticity, Plasticity, Hand Motor Cortex, Primary Motor Cortex, M1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 3 participants (estimated)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Study start
- 1 Aug 2028 (estimated)
- Primary completion
- Aug 2033 (estimated)
- Study completion
- Sep 2033 (estimated)
- First posted
- 9 Feb 2021 (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.
This study uses a cranial implant to deliver cortical stimulation that, when paired with physiotherapy, will remap the brain so that critical brain functions can be protected during brain tumor surgery. This pilot study will provide initial evidence for the safety and feasibility of such a protocol which will lead to future pivotal trials that could radically change eloquent area brain surgery. For patients with otherwise incompletely resectable brain tumors, this could mean a longer life expectancy and a better quality of life.
Detailed description
Study Protocol: Participants will undergo a standard-of-care craniotomy for resection of low-grade glioma. If part of the lesion cannot be removed due to involvement of functional cortex, RNS (Responsive Neurostimulation System [RNS; NeuroPace, Inc.]) electrodes will be implanted over the tumor-invaded area(s) in five participants. Stimulation will then be optimized for each individual to disrupt the function of the invaded cortical node (e.g., hand motor area -> hand dysfunction) (Aim 1). Over the next two months, outpatient physiotherapy will work to overcome the stim-induced deficits through gradual increases in stimulation amplitude as other, non-stimulated brain regions begin to assume its function (Aim 2). Once complete, participants will return to the OR for device explantation, repeated intraoperative mapping, and extended resection (if safe) (Aim 3).
Aim 1: Optimize stimulation to maximize stim-induced deficits and minimize side effects Rationale: To induce plasticity, stimulation parameters must be individually tuned to maximize effect and minimize side effects. Approach: After device implantation and prior to hospital discharge, stimulus settings (frequency, pulse-width, and amplitude) will be optimized to the relevant clinical response while minimizing adverse effects (e.g., focal tonus, myoclonus, or seizures) while still in the safe, inpatient setting. Outcomes: Primary Endpoints: 1) stim-induced focal clinical deficit as measured on the relevant clinical scale (e.g., manual motor score [0-5], picture naming [x/10]), repetition [x/3]); 2) stim-induced side effects (e.g., seizures).
Aim 2: Evaluate extent of remapping and safety of outpatient stimulation-physiotherapy protocol. Rationale: The ability to deliver chronic, outpatient stimulation is vital for practical clinical translation, yet neither its safety nor efficacy has been demonstrated. Approach: After Aim 1, a physiotherapist will assign a personalized, outpatient therapy regimen aimed at overcoming stim-induced deficits. Participants will have daily virtual sessions and return to clinic 2x/week for amplitude increases to re-induce deficits that therapy has overcome. This will continue until stimulation no longer can induce a deficit, suggesting successful functional remapping and enabling a return to the OR for further resection. Outcomes: Primary Endpoints: 1) absence of stim-related ER visits, readmissions, or serious adverse events (safety), 2) changes in intraop stimulation maps from surgery 1 to surgery 2 (induced remapping).
Aim 3: Evaluate ability to extend surgical resections and associated neurological outcomes. Rationale: Any change in functional boundaries will only be useful if it results in a safe, extended resection. Approach: Each surgery will proceed with standard-of-care intraoperative functional mapping techniques and decision making. Neurological examinations will be performed preoperatively, daily while inpatient, then again at 2-weeks and 3-months postoperatively. Extent of resection will be evaluated as 3D residual tumor volume on postoperative MRI. Outcomes: Primary Endpoint: 1) Change in residual tumor volume after second versus first resection, 2) new neurological deficits 3-months after second resection compared to before second resection. Secondary Endpoint: 1) New, temporary neurological deficits after the second surgery
Study design
- Primary purpose
- Device feasibility
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RNS System Implantation | Experimental | Device: RNS System ImplantationThis is a device feasibility study, therefore participants will only be enrolled into the investigational arm and will receive the RNS System Implantation. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age 18-65 years old
- Ability to understand a written informed consent document, and the willingness to sign it
- Radiographic evidence of likely low-grade glioma on MRI (i.e. non-enhancing) invading primary motor cortex in the non-dominant hemisphere.
- Karnofsky performance status (KPS) ≥ 75
- Normal or near normal motor strength (i.e., at least 3/5 in relevant areas)
Key exclusion criteria (15 listed)
- Presence of other malignancy not in remission
- Evidence of bi-hemispheric or widespread tumor involvement
- Likely candidate to receive GTR on initial resection
- Medically high-risk surgical candidate
- History of recent scalp or systemic infection
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 |
|---|---|---|
| RNS System ImplantationFollowing resection consistent with SoC, if there is evidence of residual tumor which cannot be resected due to invasion of hand-M1 but which is small enough to be covered by two four-electrode strips, these strips will be placed on the functional cortex of interest and secured to the dura. The location of the leads will be registered into the navigation software (either Medtronic Stealth or Brainlab). The dura will then be closed as watertight as possible, and the RNS System will be incorporated into the craniotomy on closure Prior to closure, four bone screws will be placed and registered to the intraoperative navigation system as internal fiducials to be retrieved for future procedures. | Device | RNS System Implantation |
Primary outcome
Extent of resection
Time frame: Within 1 week after second surgery
Calculated as: Tumor volume after second surgery - tumor volume before second surgery. Determination of volumes will be made by an attending radiologist without knowledge of clinical outcome. Manual segmentation will be performed to measure tumor volumes based on fluid-attenuated inversion recovery (FLAIR) axial slices.
Stimulation-induced motor deficits
Time frame: Within 2 weeks after first surgery
Calculated as manual muscle score (MMS) before stimulation - MMS after stimulation. MMS is a zero-to-five scale assessed as the following: 5 - normal strength 4 - give away weakness 3 - movement against gravity 2 - movement in anti-gravity position 1 - muscle twitch 0 - no movement
Stimulation-induced language deficits
Time frame: Within 2 weeks after first surgery
3a. Calculated as picture naming score (x/10) before stimulation minus after stimulation. 3b. Calculated as sentence repitition score (x/3) before stimulation minus after stimulation.
Stimulation-induced side effects
Time frame: Within 2 weeks after first surgery
Reported as number of unintended stimulation effects, such as myoclonus, tonus, seizures, or unpleasant sensations
Safety of outpatient stimulation-therapy protocol
Time frame: Up to 8 weeks
Reported as number of stimulation- or physiotherapy related ER visits, readmissions, or serious adverse events
Stimulation-induced brain remapping
Time frame: This data will be obtained intraoperatively during the second surgery
This outcome will be reported as a descriptive variable, calculated as changes in the intraoperative stimulation map obtained during surgery 2 compared to surgery 1
Number of participants with a new neurological deficit
Time frame: Assessed at 3-month postoperative visit after second surgery
Any new, permanent neurological deficits resulting from the second surgery
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 13 Oct 2026.
Related trials for Glioma
Active, not recruitingPhase 1/2
Ultrasound-based Blood-brain Barrier Opening and Albumin-bound Paclitaxel and Carboplatin for Recurrent Glioblastoma
Glioblastoma, Gliosarcoma
RecruitingPhase 2
Dabrafenib and Trametinib for BRAF V600 Mutant Low-Grade Gliomas
BRAF V600 Mutation, Low-grade Glioma
RecruitingPhase 2
Temozolomide, With or Without WSD0922-FU, for the Treatment of EGFR-Mutant, IDH-Wildtype Glioblastoma
Glioblastoma, IDH-Wildtype
Active, not recruitingPhase 1
Safety and Efficacy Study of Anti-B7-H3 CAR-T Cell Therapy for Recurrent Glioblastoma
Glioblastoma
Active, not recruitingPhase 2
A Study Testing the Effect of Immunotherapy (Ipilimumab and Nivolumab) in Patients With Recurrent Glioma With Elevated Mutational Burden
Astrocytoma, IDH-Mutant, Grade 4, Diffuse Glioma
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.
Max Krucoff, MD principal investigator
Medical College of Wisconsin
Questions about this trial
What is this clinical trial studying?
A study testing RNS System Implantation in people with Glioma and Glioma Intracranial, run by Medical College of Wisconsin.
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 8 inclusion and 15 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: opening soon, as of the sponsor's last update on 13 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
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 Sarah Cornell (414-955-0989, scornell@mcw.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Extent of resection (time frame: Within 1 week after second surgery). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Oct 2026.