CompletedNCT03029884Updated Aug 4, 2026Results posted

Closed-loop Deep Brain Stimulation to Treat Refractory Neuropathic Pain

An interventional study of Open-Loop DBS and Sham Stimulation in Chronic Pain, Post Stroke Pain and Phantom Limb Pain, sponsored by Prasad Shirvalkar, MD, PhD. Completed at 1 site in United States. Open to participants aged 21 Years and older. Per ClinicalTrials.gov, last updated 2026-08-04.

Sponsored by Prasad Shirvalkar, MD, PhD · Not applicable, Interventional, and Treatment

Phase: Not applicable
Study type: Interventional
Enrollment: 4
Allocation: Randomized
Ages: 21 Years and older
Sex: All

Study 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. 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.

Conditions studied

Chronic Pain
Post Stroke Pain
Phantom Limb Pain
Spinal Cord Injuries

Browse trials for

Keywords

thalamic pain
chronic pain
spinal cord injury
phantom limb

In context

Chronic Pain

3,227 studies on the registry are indexed under Chronic Pain; 729 are open to participants now.

This study's enrollment of 4 is below the median of 60 across 2,388 interventional studies indexed under Chronic Pain.

Browse Chronic Pain studies →

Lead sponsor

This is the only study on the registry with Prasad Shirvalkar, MD, PhD as lead sponsor.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 21 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

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 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 severe pain (see below)
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
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 method(s).

Exclusion criteria

Exclusion Criteria:

Study subjects will be adults with chronic neuropathic pain.
Pregnancy or breast feeding
Inability to speak and / or read English
Inability to give
Significant cognitive impairment or Dementia ( \< 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.
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, state or with \< 5 years
Inability to stop Coumadin or 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 to materials in the Activa PC+S system (i.e. titanium, polyurethane, silicone, polyetherimide, stainless steel).
Pregnancy or lack of regular use of . 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.

Terms in these criteria, in plain language(10)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

Relapsed and refractory

Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

MMSE and MoCA

Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.

Immunosuppression

A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.

Read whether the line is about a condition or about medicines, and which medicines and doses it means.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

Life expectancy

The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

Hypersensitivity

An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.

Study design

Phase: Not applicable
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover assignment
Masking: Single (Participant)
Enrollment: 4 participants (actual)

Study arms

Experimental
Sham DBS
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.
Device: Sham Stimulation
Experimental
Open-Loop DBS and Closed-Loop DBS
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.
Device: Open-Loop DBS · Device: Closed-Loop DBS

Interventions

DeviceOpen-Loop DBS
Conventional brain stimulation that is tonically providing stimulation, without feedback
DeviceSham Stimulation
No Active Stimulation
DeviceClosed-Loop DBS
Feedback enabled brain stimulation, where stimulation is provided on demand in response to pain biomarkers.

What researchers measure

Primary outcomes

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.
Time frame: 2 years

Secondary outcomes

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.
Time frame: 4 years

Other outcomes

Becks Depression Inventory
The Becks Depression Inventory is commonly used assessment tools to quantify and track depression mood state over time. Its a single value outcome measurement ranging from 0 to 63, with 63 being the most depressed.
Time frame: 4 years
Becks Anxiety Inventory
The Becks Anxiety Inventory is commonly used assessment tools to quantify and track anxious mood state over time.Its a single value outcome measurement ranging from 0 to 63, with 63 the most anxious.
Time frame: 4 years
NIH PROMIS Toolbox (Patient Impression)
The NIH PROMIS toolbox contains a host of survey questions tailored to measurement of specific disease states such as pain, global health and function. The patient impression evaluates patient self-evaluation and physician evaluation of the patient's general health ranging form 0 to 7 with 7 being the worst general health.
Time frame: 4 years
Pain Medication Usage
We will calculate total number of of breakthrough pain medication pills (eg. opioids, NSAIDs and neuropathic pain medication) used each month, to evaluate if analgesia from DBS reduces average usage.
Time frame: 4 years
Activity Tracker (Fitbit) - Heartrate
Each patient will be given a fitbit activity monitor which can record steps taken, flights of stairs climbed, heart rate and sleep quality. These measures will be used to infer functional improvement over time. Heartrate will be tracked as beats per minute (bpm) and the association of bpm with changes in NRS pain will be used to correlate changes in heartrate with pain levels.
Time frame: 4 years

Results

Posted Nov 22, 2023

Participant flow

Recruitment was done through the UCSF Pain management clinic and online from clinicaltrials.gov from October 2017 to December 2019

Inactive DBS Run in Period (6 months)

Participant flow — Inactive DBS Run in Period (6 months)
Milestone	Open vs Closed Loop vs Sham DBS
Started	4
Completed	4
Not completed	0

Open-Loop DBS (6 weeks)

Participant flow — Open-Loop DBS (6 weeks)
Milestone	Open vs Closed Loop vs Sham DBS
Started	4
Completed	4
Not completed	0

Closed-Loop DBS (6 weeks)

Participant flow — Closed-Loop DBS (6 weeks)
Milestone	Open vs Closed Loop vs Sham DBS
Started	4
Completed	4
Not completed	0

Sham DBS (3 weeks)

Participant flow — Sham DBS (3 weeks)
Milestone	Open vs Closed Loop vs Sham DBS
Started	4
Completed	4
Not completed	0

Outcome measures

PrimaryVisual 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.

Time frame:: 2 years
Reported as:: Median · units on a scale (millimeters)

Visual Analog Score
units on a scale (millimeters)	Inactive DBS Run in Period	Open Loop DBS	Closed Loop DBS	Sham
Visual Analog Score	76 (50 to 100)	74 (22 to 100)	75 (50 to 100)	75 (61 to 100)

SecondaryNeuropathic 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.

Time frame:: 4 years