Closed-Loop Deep Brain Stimulation for Refractory Chronic Pain

  • STATUS
    Recruiting
  • End date
    Oct 24, 2024
  • participants needed
    10
  • sponsor
    University of California, San Francisco
Updated on 15 February 2022
analgesia
stroke
chronic pain
pain disorder
pain syndromes
spinal cord
injuries
limb pain
neuropathic pain
brain stimulation
spinal cord disorder
neuralgia
multiple sclerosis
facial pain
nerve crush
postherpetic neuralgia
complex regional pain syndrome
crush injury
radiation plexopathy

Summary

Chronic pain affects 1 in 4 US adults, and many cases are resistant to almost any treatment. Deep brain stimulation (DBS) holds promise as a new option for patients suffering from treatment-resistant chronic pain, but traditional approaches target only brain regions involved in one aspect of the pain experience and provide continuous 24/7 brain stimulation which may lose effect over time. By developing new technology that targets multiple, complimentary brain regions in an adaptive fashion, the investigators will test a new therapy for chronic pain that has potential for better, more enduring analgesia.

Description

A diverse array of chronic pain syndromes are refractory to almost all treatment but involve pathological activity in similar brain regions. This suggests therapeutic potential for deep brain stimulation (DBS) for refractory pain disorders, but despite early promise, long-term efficacy is lacking. Current DBS devices are limited in anatomical reach, targeting only a subset of the distinct brain regions known to be important. Further, DBS therapy is bluntly applied in an "open-loop," continuous fashion without regard to underlying physiology. As a result of these shortcomings, DBS for pain is often ineffective or shows diminished effect over time. Loss of therapeutic effect may be due to nervous system adaptation or a failure of stimulation to accommodate patient- specific dynamics of pain processing. DBS could be significantly improved by seeking individually optimized brain targets or by using neural biomarkers of pain to selectively control stimulation when it is needed ("closed-loop" DBS). Better brain targets would also address the different dimensions of pain such as somatosensory (location, intensity and duration), affective (mood and motivation) and cognitive (attention and memory). The main goal of this study is to test the feasibility of personalized targeting of brain regions that support multiple pain dimensions and to develop new technology for "closed-loop" DBS for pain. The study team will develop data-driven stimulation control algorithms to treat chronic pain using a novel device (Medtronic Summit RC+S) that allows longitudinal intracranial signal recording in an ambulatory setting. By building this technology in an implanted device, chronic pain DBS is tailored to each patient and will advance precision methods for DBS more generally.

Beginning with an inpatient trial period, subjects with various refractory chronic pain syndromes will undergo bilateral surgical implant of temporary electrodes in the thalamus, anterior cingulate, prefrontal cortex, insula and amygdala. These regions have been implicated in the multiple dimensions of pain. The goal of the trial period is to identify candidate biomarkers of pain and optimal stimulation parameters for each individual, and to select subjects who show likelihood to benefit from the trial. A subgroup of 6 such patients will then proceed to chronic implantation of up to 3 "optimal" brain regions for long-term recording and stimulation. The invstigators will first validate biomarkers of low- and high-pain states to define neural signals for pain prediction in individuals (Aim 1). The investigators will then use these pain biomarkers to develop personalized closed-loop algorithms for DBS and test the feasibility of performing closed-loop DBS for chronic pain in weekly blocks (Aim 2). Finally, the investigators will assess efficacy of closed-loop DBS algorithms against traditional open-loop DBS or sham in a double-blinded crossover trial (Aim 3) and measure mechanisms of DBS tolerance. Our main outcome measures will be a combination of pain, mood and functional scores together with quantitative sensory testing. Successful completion of this study would result in the first algorithms to predict real-time fluctuations in chronic pain states and development of a new therapy for currently untreatable diseases.

Details
Condition Spinal Cord Injuries, Nerve Injury, Pain, Postoperative, Post Herpetic Neuralgia, Complex Regional Pain Syndromes, Post-Stroke Pain, Post Radiation Brain Injury, Post Radiation Plexopathy, Nerve Root Avulsion
Treatment Medtronic Summit RC+S
Clinical Study IdentifierNCT04144972
SponsorUniversity of California, San Francisco
Last Modified on15 February 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Age 22-80 years old
Clinical diagnosis of a refractory chronic pain syndrome including
post-traumatic pain syndromes (e.g. root avulsions, nerve crush injuries, spinal cord injury)
postsurgical pain syndromes (e.g., postmastectomy syndrome, post-thoracotomy syndrome, phantom limb pain, post-surgical spinal pain)
postherpetic neuralgia
complex regional pain syndrome
atypical facial pain
central pain syndromes (e.g. post-stroke pain, multiple sclerosis pain, post-radiation pain)
post-radiation plexopathy
Two or more years or more of medically refractory severe pain
Average daily pain for the past 30 days reported as >6 on a 0-10 numeric rating scale (NRS)
Pain that fluctuates over a range of at least 3 points on the NRS
Patient has failed at least two pain medications from different classes as determined by a neurologist or pain management specialist with stable doses of medications for 30 days prior to baseline visit
Lack of a surgically correctible etiology for the pain as determined by 2 independent surgeons
Ability to speak / read English
Capable of understanding and providing informed consent
Absence of significant cognitive impairment - score of 25 or greater on the Montreal Cognitive Assessment (MoCA)
Successful detection of pain biomarkers or positive symptomatic response to inpatient stimulation trial period if performed

Exclusion Criteria

Major medical co-morbidities increasing the risk of surgery including uncontrolled hypertension, coagulopathy, severe diabetes, major organ system failure, active infection or history of implant related infections, immunocompromised state or malignancy with < 5 years life expectancy
Presence of cardiac pacemakers/defibrillators, implanted medication pumps, intra-cardiac lines, any intracranial implants (e.g., aneurysm clip, shunt, cochlear implant, electrodes) or other implanted stimulators not compatible with RC+S system
Pregnancy or breast feeding: all women of child bearing potential will have a negative urine pregnancy test prior to undergoing their surgical procedure
Active depression (BDI > 20), Suicide attempt </= 12 months or imminent suicide risk, or other untreated or uncontrolled psychiatric illness that evaluating psychiatrist would recommend exclusion of patient after neuropsychiatric evaluation
History of substance abuse in past 3 years
Inability to stop anticoagulation or platelet anti-aggregation therapy for surgery and recovery
Implantable hardware not compatible with MRI or with the study
MR abnormalities that suggest an alternative diagnosis or contraindicate surgery
Previous cranial ablative surgery
Previous deep brain stimulation surgery using an RC+S incompatible system
Major neurological disorder other than the one that led to the chronic pain including epilepsy or a neurodegenerative condition including inability to recharge the device
Requires diathermy, electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS)
Allergies or known hypersensitivity to materials in the Summit RC+S system
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
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