Chronic PainNCT03029884
Closed-loop Deep Brain Stimulation to Treat Refractory Neuropathic Pain
A study testing Open-Loop DBS and Closed-Loop DBS in people with Chronic Pain and Post Stroke Pain, run by Prasad Shirvalkar, MD, PhD at 1 site in United States.
Trial summary
Deep brain stimulation (DBS) holds promise as a new option for patients suffering from treatment-resistant chronic pain, but current technology is unable to reliably achieve long-term pain symptom relief. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Chronic Pain, Post Stroke Pain, Phantom Limb Pain
- What is being tested?
- Open-Loop DBS and Closed-Loop DBS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Oct 2017to 30 Jun 2026
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 21 years
- Clinical diagnosis of post-stroke pain (thalamic pain), spinal cord injury or phantom limb pain with allodynia or dysesthesia with pinprick anesthesia or hypoesthesia on the affected hemibody or limb (anesthesia dolorosa).
- For Post-Stroke Pain: Stroke of ischemic etiology only. MRI done within one year of the first visit showing a lesion that involves the contralateral brainstem, thalamus or cortex. The lesion will involve cortical-subcortical areas in topography consistent with sensory thalamocortical connections. This will include patients with infarcts in the territory of the middle cerebral artery or those with cavernous malformations. A more recent MRI may be required if the patient's condition changed within the previous year.
- For Phantom limb pain: MRI done within one year not showing any contraindication to surgery such as mass, lesion, hemorrhage or other abnormality near target
- For Spinal Cord Injury pain: MRI done within one year not showing contraindication to surgery such as mass, lesion, hemorrhage or other abnormality near target
- One year or more of medically refractory severe pain (see below)
Show all 12Show fewer
- Average daily pain for the past 30 days reported as >5 on a 0-10 numeric rating scale (NRS)
- Failure to respond adequately to at least one antidepressant, one anti-seizure medication and one oral narcotic with current stable doses of medications.
- Ability to speak / read English
- Capable of understanding and providing informed consent
- Stable doses of pain medications (e.g. anticonvulsant drug, anti-depressants, and opioids etc.)
- Women of childbearing age must be on regular use of an accepted contraceptive method(s).
Who cannot join
- Study subjects will be adults with refractory chronic neuropathic pain.
- Pregnancy or breast feeding
- Inability to speak and / or read English
- Inability to give informed consent
- Significant cognitive impairment or Dementia (MoCA < 25)
- Aphasia severe enough to limit the consent process or communication between the investigators and the patient. Patients with mild or recovering aphasia may be considered candidates at the discretion of the PI.
Show all 23Show fewer
- Active depression (BDI > 20) or other untreated or uncontrolled psychiatric illness (active general anxiety disorder, schizophrenia, bipolar disorder, obsessive-compulsive disorder (OCD), or personality disorders (e.g. multiple personality disorder, borderline personality disorder, etc.) or other neuropsychiatric conditions that evaluating psychiatrist would recommend exclusion of patient after neuropsychiatric evaluation.
- Suicide attempt </= 12 months or imminent suicide risk
- History of substance abuse in past 3 years.
- Major medical co-morbidities increasing the risk of surgery including uncontrolled hypertension, severe diabetes, major organ system failure, history of hemorrhagic stroke, need for chronic anticoagulation other than aspirin, active infection, immunocompromised state or malignancy with < 5 years life expectancy
- Inability to stop Coumadin or platelet anti-aggregation therapy for surgery and after surgery. Patients taking these medications will need to discuss the need/risk of continuing these medications with their physicians and the PI or study personnel may contact the treating physician(s) as well to discuss the risks of anticoagulation / antiaggregation therapy discontinuation.
- Coagulopathy. Patients will be excluded unless assessed and cleared by hematology.
- MRI (done within one year of the first visit) with significant abnormalities other than those associated with the neurological disorder causing chronic pain.
- Implantable hardware not compatible with MRI or with the study.
- Inability to comply with study follow-up visits
- Previous ablative intracranial surgery for the management of the thalamic pain syndrome.
- Previously implanted with deep brain stimulation system or any previously implanted device treatment involving brain stimulation
- Major neurological disorder other than the one that led to the chronic pain including epilepsy, neurodegenerative condition or any history of seizure
- Requires diathermy, electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) to treat a chronic condition
- Has an implanted electronic device such as a neurostimulator, cardiac pacemaker or medication pump
- Allergies or known hypersensitivity to materials in the Activa PC+S system (i.e. titanium, polyurethane, silicone, polyetherimide, stainless steel).
- Pregnancy or lack of regular use of contraceptives. Patients who become pregnant after enrollment may be excluded from the study. Patients who become pregnant prior to the surgical implantation of the DBS systems will be excluded from the study.
- Patients may be excluded from enrollment due to a condition that, in the judgment of the PI, significantly increases risk or reduces significantly the likelihood of benefit from DBS.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California
San Francisco, California, 94143
About this study
Official title: Technology Development for Closed-loop Deep Brain Stimulation to Treat Refractory Neuropathic Pain
Deep brain stimulation (DBS) holds promise as a new option for patients suffering from treatment-resistant chronic pain, but current technology is unable to reliably achieve long-term pain symptom relief. A "one-size-fits-all" approach of continuous, 24/7 brain stimulation has helped patients with some movement disorders, but the key to reducing pain may be the activation of stimulation only when needed, as this may help keep the brain from adapting to stimulation effects. By expanding the technological capabilities of an investigative brain stimulation device, the investigators will enable the delivery of stimulation only when pain signals in the brain are high, and then test whether this more personalized stimulation leads to reliable symptom relief for chronic pain patients over extended periods of time.
Read the detailed description
Many pain syndromes are notoriously refractory to almost all treatment and pose significant costs to patients and society. Deep brain stimulation (DBS) for refractory pain disorders showed early promise but demonstration of long-term efficacy is lacking. Current DBS devices provide "open-loop" continuous stimulation and thus are prone to loss of effect owing to nervous system adaptation and a failure to accommodate natural fluctuations in chronic pain states. DBS could be significantly improved if neural biomarkers for relevant disease states could be used as feedback signals in "closed-loop" DBS algorithms that would selectively provide stimulation when it is needed. This approach may help avert the development of tolerance over time and enable the dynamic features of chronic pain to be targeted in a personalized fashion.
Optimizing the brain targets for both biomarker detection and stimulation delivery may also markedly impact efficacy. Recent imaging studies in humans point to the key role of frontal cortical regions in supporting the affective and cognitive dimensions of pain, which may be more effective DBS targets than previous targets involved in basic somatosensory processing. Pathological activity in the anterior cingulate (ACC) and orbitofrontal cortex (OFC) is correlated with the higher-order processing of pain, and recent clinical trials have identified ACC as a promising stimulation target for the neuromodulation of pain. In this study, the investigators will target ACC and OFC for biomarker discovery and closed-loop stimulation. The investigators will develop data-driven stimulation control algorithms to treat chronic pain using a novel neural interface device (Medtronic Activa PC+S) that allows longitudinal intracranial signal recording in an ambulatory setting. By building and validating this technological capacity in an implanted device, the investigators will empower DBS for chronic pain indications and advance personalized, precision methods for DBS more generally.
This study will enroll ten patients with post-stroke pain, phantom limb syndrome and spinal cord injury pain in our three-phase clinical trial. The investigators will first identify biomarkers of low and high pain states to define optimal neural signals for pain prediction in individuals (Aim 1). These pain biomarkers will then be used to develop closed-loop algorithms for DBS and test the feasibility and efficacy of performing closed-loop DBS for chronic pain in a single-blinded, sham controlled clinical trial (Aim 2). Our main outcome measures will be a combination of pain, mood and functional scores together with quantitative sensory testing. In the last phase, the investigators will assess the efficacy of closed-loop DBS algorithms against traditional open-loop DBS (Aim 3) and assess mechanisms of DBS tolerance in response to chronic stimulation. Successful completion of this study would result in the first algorithms to predict real-time fluctuations in chronic pain states for the delivery of analgesic stimulation and would prove the feasibility of closed-loop DBS for pain-relief by advancing implantable device technology.
- Being tested
- Open-Loop DBS, Sham Stimulation, Closed-Loop DBS
- Keywords
- thalamic pain, chronic pain, spinal cord injury, phantom limb
- Medical subject headings
- Chronic Pain, Phantom Limb, Spinal Cord Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Open-Loop DBSDevice
Conventional brain stimulation that is tonically providing stimulation, without feedback
Sham StimulationDevice
No Active Stimulation
Closed-Loop DBSDevice
Feedback enabled brain stimulation, where stimulation is provided on demand in response to pain biomarkers.
| Study group | Role | What they receive |
|---|---|---|
| Sham DBS | Experimental | Chronic brain recording and stimulation with unilateral or bilateral implantation in pain-related brain regions. Both thalamic pain syndrome and phantom pain participants will participate in sham, open-loop and closed-loop DBS, blinded to the participant.
Open Loop involves tonic stimulation of ACC of OFC brain region. During closed-loop DBS sessions, stimulation will be delivered in response to identified personalized, brain biomarkers of chronic pain.Sham involves no active stimulation - brain recordings will remain active with no active stimulation. Because more than 6 sequences were used, only 1 "Arm/Group" is defined. Receives: Device: Sham Stimulation |
| Open-Loop DBS and Closed-Loop DBS | Experimental | Chronic brain recording and stimulation with unilateral or bilateral implantation in pain-related brain regions. Both thalamic pain syndrome and phantom pain participants will participate in sham, open-loop and closed-loop DBS, blinded to the participant.
Open Loop involves tonic stimulation of ACC of OFC brain region. During closed-loop DBS sessions, stimulation will be delivered in response to identified personalized, brain biomarkers of chronic pain.Sham involves no active stimulation - brain recordings will remain active with no active stimulation. Because more than 6 sequences were used, only 1 "Arm/Group" is defined. Receives: Device: Open-Loop DBS; Device: Closed-Loop DBS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Visual Analog Score
Visual Analog Score is indicated by the patient by marking a 10 cm line as they rate their pain intensity from 0 to 100 in mm. Higher scores represent worse outcome.
Measured: 2 years
Secondary outcomes (1)
Neuropathic Pain Questionnaire
The Neuropathic pain Questionnaire (NPQ) is an assessment instrument for neuropathic pain intensity and quality. It contains 12 items: 10 related to sensations or sensory responses and two related to affect. The items are totaled and rated out of 12, with 12 being in the most neuropathic pain.
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2017 (estimated)
- Study start28 Oct 2017
- Primary completion30 Sep 2023
- Study completion30 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic PainStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- All participants (phantom limb and thalamic pain) will participate in the same three phase study to test open-loop DBS vs closed-loop DBS vs Sham DBS
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Prasad Shirvalkar, MD, PhD
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense, National Institute of Neurological Disorders and Stroke (NINDS)
- Responsible party
- Sponsor-investigator, Prasad Shirvalkar, MD, PhD, University of California, San Francisco
- Investigators
- Edward Chang, M.D., Principal investigator, University of California, San FranciscoPrasad Shirvalkar, M.D., Ph.D., Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03029884
- Sponsor's protocol ID
- 16-18617
- Other IDs
- UH3NS109556
- Status last verified
- Jul 2026
- First submitted
- 6 Jan 2017
- Last updated
- 4 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No: There is currently no plan to share IPD.
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Technology Development for Closed-loop Deep Brain Stimulation to Treat Refractory Neuropathic Pain
- ClinicalTrials.gov ID
- NCT03029884
- Acronym / sponsor ID
- 16-18617
- Keywords
- thalamic pain, chronic pain, spinal cord injury, phantom limb
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Prasad Shirvalkar, MD, PhDUniversity, hospital or other
- Collaborators
- United States Department of Defense, National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- 28 Oct 2017 (actual)
- Primary completion
- 30 Sep 2023 (actual)
- Study completion
- 30 Jun 2026 (actual)
- First posted
- 24 Jan 2017 (estimated)
- Results
- Posted 22 Nov 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Deep brain stimulation (DBS) holds promise as a new option for patients suffering from treatment-resistant chronic pain, but current technology is unable to reliably achieve long-term pain symptom relief. A "one-size-fits-all" approach of continuous, 24/7 brain stimulation has helped patients with some movement disorders, but the key to reducing pain may be the activation of stimulation only when needed, as this may help keep the brain from adapting to stimulation effects. By expanding the technological capabilities of an investigative brain stimulation device, the investigators will enable the delivery of stimulation only when pain signals in the brain are high, and then test whether this more personalized stimulation leads to reliable symptom relief for chronic pain patients over extended periods of time.
Detailed description
Many pain syndromes are notoriously refractory to almost all treatment and pose significant costs to patients and society. Deep brain stimulation (DBS) for refractory pain disorders showed early promise but demonstration of long-term efficacy is lacking. Current DBS devices provide "open-loop" continuous stimulation and thus are prone to loss of effect owing to nervous system adaptation and a failure to accommodate natural fluctuations in chronic pain states. DBS could be significantly improved if neural biomarkers for relevant disease states could be used as feedback signals in "closed-loop" DBS algorithms that would selectively provide stimulation when it is needed. This approach may help avert the development of tolerance over time and enable the dynamic features of chronic pain to be targeted in a personalized fashion.
Optimizing the brain targets for both biomarker detection and stimulation delivery may also markedly impact efficacy. Recent imaging studies in humans point to the key role of frontal cortical regions in supporting the affective and cognitive dimensions of pain, which may be more effective DBS targets than previous targets involved in basic somatosensory processing. Pathological activity in the anterior cingulate (ACC) and orbitofrontal cortex (OFC) is correlated with the higher-order processing of pain, and recent clinical trials have identified ACC as a promising stimulation target for the neuromodulation of pain. In this study, the investigators will target ACC and OFC for biomarker discovery and closed-loop stimulation. The investigators will develop data-driven stimulation control algorithms to treat chronic pain using a novel neural interface device (Medtronic Activa PC+S) that allows longitudinal intracranial signal recording in an ambulatory setting. By building and validating this technological capacity in an implanted device, the investigators will empower DBS for chronic pain indications and advance personalized, precision methods for DBS more generally.
This study will enroll ten patients with post-stroke pain, phantom limb syndrome and spinal cord injury pain in our three-phase clinical trial. The investigators will first identify biomarkers of low and high pain states to define optimal neural signals for pain prediction in individuals (Aim 1). These pain biomarkers will then be used to develop closed-loop algorithms for DBS and test the feasibility and efficacy of performing closed-loop DBS for chronic pain in a single-blinded, sham controlled clinical trial (Aim 2). Our main outcome measures will be a combination of pain, mood and functional scores together with quantitative sensory testing. In the last phase, the investigators will assess the efficacy of closed-loop DBS algorithms against traditional open-loop DBS (Aim 3) and assess mechanisms of DBS tolerance in response to chronic stimulation. Successful completion of this study would result in the first algorithms to predict real-time fluctuations in chronic pain states for the delivery of analgesic stimulation and would prove the feasibility of closed-loop DBS for pain-relief by advancing implantable device technology.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- All participants (phantom limb and thalamic pain) will participate in the same three phase study to test open-loop DBS vs closed-loop DBS vs Sham DBS
| Arm | Type | Receives |
|---|---|---|
| Sham DBS | Experimental | Device: Sham StimulationChronic brain recording and stimulation with unilateral or bilateral implantation in pain-related brain regions. Both thalamic pain syndrome and phantom pain participants will participate in sham, open-loop and closed-loop DBS, blinded to the participant. Open Loop involves tonic stimulation of ACC of OFC brain region. During closed-loop DBS sessions, stimulation will be delivered in response to identified personalized, brain biomarkers of chronic pain.Sham involves no active stimulation - brain recordings will remain active with no active stimulation. Because more than 6 sequences were used, only 1 "Arm/Group" is defined. |
| Open-Loop DBS and Closed-Loop DBS | Experimental | Device: Open-Loop DBS, Device: Closed-Loop DBSChronic brain recording and stimulation with unilateral or bilateral implantation in pain-related brain regions. Both thalamic pain syndrome and phantom pain participants will participate in sham, open-loop and closed-loop DBS, blinded to the participant. Open Loop involves tonic stimulation of ACC of OFC brain region. During closed-loop DBS sessions, stimulation will be delivered in response to identified personalized, brain biomarkers of chronic pain.Sham involves no active stimulation - brain recordings will remain active with no active stimulation. Because more than 6 sequences were used, only 1 "Arm/Group" is defined. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Age ≥ 21 years
- Clinical diagnosis of post-stroke pain (thalamic pain), spinal cord injury or phantom limb pain with allodynia or dysesthesia with pinprick anesthesia or hypoesthesia on the affected hemibody or limb (anesthesia dolorosa).
- For Post-Stroke Pain: Stroke of ischemic etiology only. MRI done within one year of the first visit showing a lesion that involves the contralateral brainstem, thalamus or cortex. The lesion will involve cortical-subcortical areas in topography consistent with sensory thalamocortical connections. This will include patients with infarcts in the territory of the middle cerebral artery or those with cavernous malformations. A more recent MRI may be required if the patient's condition changed within the previous year.
- For Phantom limb pain: MRI done within one year not showing any contraindication to surgery such as mass, lesion, hemorrhage or other abnormality near target
- For Spinal Cord Injury pain: MRI done within one year not showing contraindication to surgery such as mass, lesion, hemorrhage or other abnormality near target
Key exclusion criteria (23 listed)
- Study subjects will be adults with refractory chronic neuropathic pain.
- Pregnancy or breast feeding
- Inability to speak and / or read English
- Inability to give informed consent
- Significant cognitive impairment or Dementia (MoCA < 25)
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 |
|---|---|---|
| Open-Loop DBSConventional brain stimulation that is tonically providing stimulation, without feedback | Device | Open-Loop DBS and Closed-Loop DBS |
| Sham StimulationNo Active Stimulation | Device | Sham DBS |
| Closed-Loop DBSFeedback enabled brain stimulation, where stimulation is provided on demand in response to pain biomarkers. | Device | Open-Loop DBS and Closed-Loop DBS |
Primary outcome
Visual Analog Score
Time frame: 2 years
Visual Analog Score is indicated by the patient by marking a 10 cm line as they rate their pain intensity from 0 to 100 in mm. Higher scores represent worse outcome.
1 secondary outcome
Neuropathic Pain Questionnaire
Time frame: 4 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. There is currently no plan to share IPD.
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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. This study is not recruiting at the moment.
Edward Chang, M.D. principal investigator
University of California, San Francisco
Prasad Shirvalkar, M.D., Ph.D. principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Open-Loop DBS and Closed-Loop DBS in people with Chronic Pain and Post Stroke Pain, run by Prasad Shirvalkar, MD, PhD at 1 site in United States.
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 12 inclusion and 23 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: finished, as of the sponsor's last update on 4 Aug 2026. 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 United States. 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?
Yes. Results are posted in the registry (first posted 22 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Visual Analog Score (time frame: 2 years). 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 4 Aug 2026.