DBS for Chronic Pain

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Francisco

Must be taking: Antidepressants, Anti-seizure, Narcotics

Disqualifiers: Pregnancy, Dementia, Active depression, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method of using deep brain stimulation (DBS) to assist individuals with chronic pain unresponsive to other treatments. The approach focuses on delivering brain stimulation only when pain signals are high, rather than continuously, to determine if it can provide better, long-lasting relief. Participants will experience different methods, including active stimulation and a placebo (sham) approach, without knowing which they receive. Individuals with severe, treatment-resistant pain for over a year due to conditions like post-stroke pain, spinal cord injury, or phantom limb pain may be suitable for this study. The trial will use the Medtronic Activa PC+S device. As an unphased trial, it offers a unique opportunity to contribute to pioneering research that could lead to innovative pain management solutions.

Will I have to stop taking my current medications?

The trial requires that participants have stable doses of their current pain medications, so you will not need to stop taking them. However, if you are on Coumadin or platelet anti-aggregation therapy, you may need to discuss with your doctor about stopping these for surgery.

What prior data suggests that this brain stimulation device is safe for chronic pain patients?

Research has shown that deep brain stimulation (DBS) with devices like the Medtronic Activa PC+S is under study as a potential treatment for chronic pain. This device already has approval for other conditions, such as epilepsy, indicating its prior safe use in people.

In studies focused on pain, the device has been used without major long-term safety issues, although its long-term effectiveness in relieving pain remains under investigation. While the device appears promising, its consistent ability to relieve pain over time is not yet fully confirmed.

The DBS process involves placing a device in specific brain areas to help manage pain signals. This technology's use in other medical areas provides some reassurance about its safety. However, like any medical treatment, side effects or unexpected issues may occur, which should be discussed with healthcare providers before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about DBS for chronic pain because it introduces a novel approach to pain management by using both open-loop and closed-loop deep brain stimulation (DBS). Unlike traditional treatments like medication or physical therapy, which primarily aim to manage symptoms, this technique targets the brain directly. Open-loop DBS provides continuous stimulation, while closed-loop DBS adapts in real-time, responding to specific brain activity linked to chronic pain. This personalized stimulation could offer more precise pain relief, potentially transforming how chronic pain is treated.

What evidence suggests that this trial's treatments could be effective for chronic pain?

This trial will compare different approaches to deep brain stimulation (DBS) for chronic pain using the Medtronic Activa PC+S device. Research has shown that DBS successfully treats some movement disorders and might also help with chronic pain. The Medtronic Activa PC+S device, used in this trial, offers a more personalized approach by providing stimulation only when brain pain signals are high. Early results suggest this "on-demand" method could be more effective because it prevents the brain from becoming accustomed to constant stimulation, which can reduce effectiveness. Systems like this have shown promise in early studies for providing reliable symptom relief over time. However, more research is needed to confirm these benefits specifically for chronic pain. Participants in this trial will experience both open-loop and closed-loop DBS, as well as sham DBS, to evaluate the effectiveness of these methods. ^{6 7 8 9 10}

Who Is on the Research Team?

Edward Chang, M.D.

Principal Investigator

University of California, San Francisco

Prasad Shirvalkar, M.D., Ph.D.

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

Adults over 21 with severe chronic pain from conditions like post-stroke pain, spinal cord injury, or phantom limb pain that hasn't improved after trying several medications. They must be able to speak/read English and women should use contraception. Excluded are those with incompatible implants, cognitive impairments, recent substance abuse, major medical issues increasing surgery risk, or who can't stop certain blood thinners.

Inclusion Criteria

I have had severe pain for over a year that medicine hasn't helped.

I haven't improved with antidepressants, anti-seizure meds, or narcotics.

I experience severe pain after a stroke, spinal injury, or amputation.

Exclusion Criteria

I cannot stop taking blood thinners for surgery.

I had brain surgery to manage pain in my thalamus.

I need special treatments like ECT or TMS for a long-term condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Biomarker Identification

Identify biomarkers of low and high pain states to define optimal neural signals for pain prediction

8-12 weeks

Closed-loop Algorithm Development

Develop closed-loop algorithms for DBS and test feasibility and efficacy in a single-blinded, sham controlled trial

6 months

Efficacy Assessment

Assess the efficacy of closed-loop DBS algorithms against traditional open-loop DBS and mechanisms of DBS tolerance

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Medtronic Activa PC+S

Trial Overview

The trial is testing a new type of brain stimulation device for chronic pain relief. It compares continuous 'open-loop' DBS (current standard), no stimulation ('sham'), and 'closed-loop' DBS which activates only when the brain signals high pain levels. The goal is to see if this personalized approach provides better long-term relief.

How Is the Trial Designed?

Group I: Sham DBS Experimental Treatment 1 Intervention

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.

Group II: Open-Loop DBS and Closed-Loop DBS Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Prasad Shirvalkar, MD, PhD

Lead Sponsor

Trials

1

Recruited

4+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Published Research Related to This Trial

Deep brain stimulation (DBS) is an established treatment for movement disorders like Parkinson's disease and has been used for pain management since the 1950s, particularly for chronic pain syndromes resistant to other treatments.

Despite past challenges and mixed results in clinical trials, DBS remains a viable option for severe facial pain and other neuropathic pain conditions, with ongoing research aimed at improving patient selection and understanding its mechanisms of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation for Facial Pain. Singleton, WGB., Ashida, R., Patel, NK.[2021]

Deep brain stimulation (DBS) has been successfully used to treat chronic pain in 100 patients over 12 years, particularly for conditions like pain after amputation, stroke, and multiple sclerosis.

The technique emphasizes the importance of somatotopic coverage during awake surgery, and advancements in neuroimaging and neurophysiological insights may improve patient selection and treatment efficacy, suggesting a need for larger clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for pain. Pereira, EA., Green, AL., Aziz, TZ.[2013]

Deep brain stimulation (DBS) has been successfully used to treat chronic neuropathic pain in 113 patients over 13 years, particularly for conditions like pain after amputation and stroke, indicating its potential as a viable treatment option for refractory pain.

The study emphasizes the importance of somatotopic coverage during awake surgery and suggests that advancements in neuroimaging and neurophysiological assessments could improve patient selection and treatment outcomes, paving the way for larger clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuropathic pain and deep brain stimulation. Pereira, EA., Aziz, TZ.[2021]

Deep brain stimulation (DBS) and Motor Cortex stimulation (MCS) are effective methods for managing chronic pain, which is often complex and challenging to treat.

The review highlights that stimulation of specific brain areas, such as the thalamus and motor cortex, can provide partial pain relief in carefully selected patients, emphasizing the importance of targeted approaches in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation and Motor Cortex Stimulation for Chronic Pain. Senatus, P., Zurek, S., Deogaonkar, M.[2021]

Citations

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clinicaltrials.gov

clinicaltrials.gov/study/NCT03029884

NCT03029884 | Closed-loop Deep Brain Stimulation to ...

The investigators will develop data-driven stimulation control algorithms to treat chronic pain using a novel neural interface device (Medtronic Activa PC+S) ...

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8716790/

Practical Closed-Loop Strategies for Deep Brain Stimulation

We offer a practical guide for the implementation of a closed-loop DBS system, using examples from patients with chronic pain.

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clinicaltrial.be

clinicaltrial.be/fr/details/9365?per_page=100&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Closed-loop Deep Brain Stimulation to Treat Refractory Ne...

The investigators will develop data-driven stimulation control algorithms to treat chronic pain using a novel neural interface device (Medtronic Activa PC+S) ...

4.

withpower.com

withpower.com/trial/phase-chronic-pain-9-2017-1eda7

DBS for Chronic Pain · Info for Participants

What data supports the effectiveness of the treatment Medtronic Activa PC+S for chronic pain? Deep brain stimulation (DBS) has shown success in treating chronic ...

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frontiersin.org

frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2018.00018/full

Closed-Loop Deep Brain Stimulation for Refractory ...

In this article we will argue that feedback-controlled 'closed-loop' deep brain stimulation (DBS) offers an urgent and promising route for treatment.

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04144972

NCT04144972 | Closed-Loop Deep Brain Stimulation for ...

This suggests therapeutic potential for deep brain stimulation (DBS) for refractory pain disorders, but despite early promise, long-term efficacy is lacking.

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5553781/

Advances in closed-loop deep brain stimulation devices

Another commercial closed-loop DBS system is the Activa PC + S which is an implantable sensing-stimulating DBS device manufactured by Medtronic.

8.

accessdata.fda.gov

accessdata.fda.gov/cdrh_docs/pdf/P960009S219b.pdf

summary of safety and effectiveness data (ssed)

The Medtronic DBS System for Epilepsy is indicated for the following: Bilateral stimulation of the anterior nucleus of the thalamus (ANT) using ...

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cdn.clinicaltrials.gov

cdn.clinicaltrials.gov/large-docs/84/NCT03029884/Prot_SAP_000.pdf

CLINICAL PROTOCOL (version 10.01.2019)

Our primary objectives are to: 1) Determine the neural correlates of increased pain states in patients with chronic pain in order to enable targeted DBS.

10.

clinicaltrial.be

clinicaltrial.be/en/details/9365?per_page=100&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Closed-loop Deep Brain Stimulation to Treat Refractory Ne...

This study will enroll ten patients with post-stroke pain, phantom limb syndrome and spinal cord injury pain in our three-phase clinical trial.