Closed-loop Deep Brain Stimulation to Treat Refractory Neuropathic Pain

NCT03029884 | Active Not Recruiting Results DMC FDA Device

• 2 other identifiers: 16-18617UH3NS109556
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Post Stroke Pain; Phantom Limb Pain; Spinal Cord Injuries; Chronic Pain

Keywords

thalamic pain; chronic pain; spinal cord injury; phantom limb

Outcome Measures

Primary Outcomes (1)

• 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.

  2 years

Secondary Outcomes (1)

• Neuropathic Pain Questionnaire

  4 years

Other Outcomes (5)

• Becks Depression Inventory

  4 years

• Becks Anxiety Inventory

  4 years

• NIH PROMIS Toolbox (Patient Impression)

  4 years

Study Arms (2)

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.

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.

Device: Open-Loop DBS; Device: Closed-Loop DBS

Interventions

Open-Loop DBS DEVICE

Conventional brain stimulation that is tonically providing stimulation, without feedback

Open-Loop DBS and Closed-Loop DBS

Sham Stimulation DEVICE

No Active Stimulation

Sham DBS

Closed-Loop DBS DEVICE

Feedback enabled brain stimulation, where stimulation is provided on demand in response to pain biomarkers.

Open-Loop DBS and Closed-Loop DBS

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• United States Department of Defense: collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• Prasad Shirvalkar, MD, PhD: lead

Study Sites (1)

University of California

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Chronic Pain; Phantom Limb; Spinal Cord Injuries

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Perceptual Disorders; Neurobehavioral Manifestations; Nervous System Diseases; Pain, Postoperative; Postoperative Complications; Pathologic Processes; Spinal Cord Diseases; Central Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries

Results Point of Contact

• Title: Prasad Shirvalkar MD, PhD - Principal Investigator
• Organization: University of California, San Francisco

Prasad.Shirvalkar@ucsf.edu

415-885-7246

Study Officials

• Edward Chang, M.D.

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Prasad Shirvalkar, M.D., Ph.D.

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: There will be assigned active intervention and non-active intervention periods for each patient throughout phase 2 and 3 of the study. The participant will not know if he/she is in the active or non-active period of the phase.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Neurological Surgery

Model Details: 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

Study Record Dates

• First Submitted: January 6, 2017
• First Posted: January 24, 2017
• Study Start: October 28, 2017
• Primary Completion: September 30, 2023
• Study Completion: June 1, 2026
• Last Updated: April 8, 2026
• Results First Posted: November 22, 2023

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)