Deep Brain Stimulation for Chronic Pain

Overseen By Catherine Borror

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Francisco

Disqualifiers: Uncontrolled hypertension, Severe diabetes, Active depression, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new deep brain stimulation (DBS) technology, specifically the Medtronic Summit RC+S, for treating chronic pain unresponsive to usual medications. The approach targets multiple brain areas involved in pain to potentially provide longer-lasting relief. Participants will receive either active brain stimulation or a non-active version to compare results. Ideal participants are those who have experienced severe, treatment-resistant chronic pain for more than two years and have tried at least two different pain medications without success. As an unphased trial, this study offers patients the opportunity to contribute to groundbreaking research that could lead to new pain management solutions.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that participants should have stable doses of medications for 30 days prior to the baseline visit, which suggests you may need to maintain your current medication regimen.

What prior data suggests that this device is safe for chronic pain treatment?

Research shows that the Medtronic Summit RC+S, a device for deep brain stimulation, has FDA approval for sensing brain activity. This approval indicates its safety for use in people with other conditions. Several ongoing studies are examining the safety and effectiveness of similar deep brain stimulation systems for other conditions. Although specific data on side effects for chronic pain is not yet available, existing approvals and ongoing research in related areas suggest that the treatment is generally well-tolerated. However, as with any medical treatment, risks may exist, and participants should discuss possible side effects with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Deep Brain Stimulation (DBS) for chronic pain because it offers a novel approach to pain management that could be life-changing for patients. Unlike traditional pain treatments like opioids or nerve blocks, DBS targets specific brain regions associated with pain perception, potentially offering more precise relief with fewer side effects. The Medtronic Summit RC+S device used in this trial not only stimulates the brain but also records brain activity, allowing for a more personalized and adaptive treatment. This dual capability could lead to a deeper understanding of chronic pain and more effective long-term treatment strategies.

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

Research has shown that deep brain stimulation (DBS) could be a promising treatment for chronic pain unresponsive to other therapies. Early results suggest that DBS reduces pain by sending electrical signals to specific brain areas involved in pain processing. In this trial, participants will join either an active DBS arm or an inactive DBS arm. The Medtronic Summit RC+S device, used in the active DBS arm, has shown promise in managing chronic pain by adjusting its signals based on real-time brain activity. This new technology aims to provide more effective and lasting pain relief by targeting several brain areas involved in pain perception. Early experiences with similar devices have shown positive results, suggesting that this method could offer significant benefits for people with chronic pain unresponsive to other treatments. ^{1 6 7 8 9}

Who Is on the Research Team?

Prasad Shirvalkar, M.D., Ph.D

Principal Investigator

University of California, San Francisco

Edward Chang, M.D.

Principal Investigator

University of California, San Francisco

Philip Starr, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for adults aged 22-80 with severe, treatment-resistant chronic pain from conditions like post-traumatic or postsurgical syndromes, nerve injuries, and more. Participants must have had this pain for over two years, failed at least two different pain medications, and not have a correctible cause for the pain. They should be able to understand English and consent to the study. Pregnant women or those with certain medical devices or major health issues can't join.

Inclusion Criteria

My pain level changes by 3 or more points.

You have to score 25 or more on a test called the Montreal Cognitive Assessment (MoCA) to show that your memory and thinking abilities are at a certain level.

I have tried at least two different pain medications for a month without relief.

Exclusion Criteria

I have had brain surgery to remove a tumor.

I cannot stop my blood thinners for surgery and recovery.

I had deep brain stimulation surgery with a system not compatible with RC+S.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Inpatient Trial Period

Subjects undergo bilateral surgical implant of temporary electrodes to identify candidate biomarkers of pain and optimal stimulation parameters

4 weeks

Inpatient stay

Chronic Implantation and Closed-loop DBS Testing

Subgroup of patients receive chronic implantation for long-term recording and stimulation, testing closed-loop DBS algorithms

2 years

Weekly blocks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Medtronic Summit RC+S

Trial Overview The trial tests a new Deep Brain Stimulation (DBS) device called Medtronic Summit RC+S designed to adaptively target multiple brain regions related to chronic pain. Unlike traditional DBS that stimulates continuously which may lose effect over time, this technology aims for lasting relief by adjusting stimulation as needed.

How Is the Trial Designed?

Group I: Active DBS Active Control 1 Intervention

Chronic brain recordings and stimulation with bilateral implantations in pain-related brain regions. All participants will participate in active DBS, blinded to the participant.

Group II: Inactive DBS Placebo Group 1 Intervention

Non-active chronic brain stimulation in pain-related brain regions. brain recordings will remain active during this period. All participants will participate in inactive DBS, blinded to the participant.

Medtronic Summit RC+S is already approved in United States, European Union for the following indications:

Approved in United States as Medtronic Summit RC+S for:

• Chronic pain
• Post-stroke pain
• Phantom limb pain
• Spinal cord injury pain

Approved in European Union as Medtronic Summit RC+S for:

• Chronic pain
• Neuropathic pain
• Refractory chronic pain

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Published Research Related to This Trial

Out of 30 patients who received self-stimulating devices for pain control, 66% (18 patients) experienced significant pain relief, indicating a successful outcome for the majority of those implanted.

The stimulation was effective for brief periods (5 to 30 minutes every 2 to 12 hours) and was associated with minimal side effects and a low complication rate, suggesting it is a safe option for chronic pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long term results of periventricular gray self-stimulation. Richardson, DE., Akil, H.[2019]

Deep brain stimulation (DBS) is an effective treatment for chronic pain that does not respond to other therapies, showing long-term positive outcomes in 50% to 80% of patients, depending on the type of pain and stimulation site.

The most successful results are observed in patients with deafferentation pain when stimulating the internal capsule and in those with somatic pain when using periventricular stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for the relief of chronic pain. Richardson, DE.[2011]

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]

In a study of 48 patients with chronic pain, deep brain stimulation achieved long-term pain control in 63% of cases, with follow-up periods ranging from 6 months to 10 years.

While there is an initial decline in pain control within the first 2 years due to tolerance, results stabilize afterward, indicating that deep brain stimulation can be a safe and effective option for selected patients, particularly those with failed-back syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for control of intractable pain in humans, present and future: a ten-year follow-up. Kumar, K., Wyant, GM., Nath, R.[2019]

Motor cortex stimulation (MCS) has been shown to be a safe and effective treatment for facial chronic neuropathic pain (FCNP), with 84% of patients achieving good pain control after permanent implantation of the system.

A total of 118 patients were reviewed, but the evidence is still limited due to the need for larger randomized controlled studies to establish MCS as a standard treatment for FCNP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Motor cortex stimulation for facial chronic neuropathic pain: A review of the literature. Monsalve, GA.[2021]

Motor cortex stimulation (MCS) in two patients with complex regional pain syndrome (CRPS) not only provided significant pain relief (60-70% reduction in pain scores) but also improved sensory and motor functions, which is a notable advantage over traditional spinal cord stimulation.

Long-term benefits were observed, including increased joint range of motion and reduced symptoms like allodynia and hyperpathia, suggesting that MCS may positively affect brain regions involved in pain processing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pain relief and functional recovery in patients with complex regional pain syndrome after motor cortex stimulation. Fonoff, ET., Hamani, C., Ciampi de Andrade, D., et al.[2011]

A new cerebral stimulation technique for chronic pain was tested on nine patients, where a small electrode was implanted to allow patients to control their pain relief using a portable stimulator.

The method effectively suppressed pain for up to seven hours with minimal complications, making it a safer and reversible alternative to traditional coagulation methods for treating chronic intractable pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of chronic pain with intracerebral stimulators]. Mundinger, F.[2006]

The Medtronic 'Percept' device, the first FDA-approved deep brain stimulation system with sensing capabilities, was tested on 7 subjects to identify and mitigate artifacts in local field potential signals that could affect its performance.

Using automated template subtraction techniques, researchers successfully removed various artifacts, such as ECG signals and nonphysiologic noise, which could otherwise distort the neural signals and impact the effectiveness of adaptive deep brain stimulation algorithms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Artifact Characterization and a Multipurpose Template-Based Offline Removal Solution for a Sensing-Enabled Deep Brain Stimulation Device. Hammer, LH., Kochanski, RB., Starr, PA., et al.[2023]

Deep brain stimulation of the thalamus and internal capsule significantly improved various conditions including pain, hemiparesis, dystonia, tremor, speech impairment, and epilepsy.

Effective stimulation requires precise voltage settings (around 6 V) and timing, as deviations from these parameters can lead to a loss of clinical benefits, highlighting the importance of accurate 'biocalibration' for optimal results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reversibility of chronic neurologic deficits. Some effects of electrical stimulation of the thalamus and internal capsule in man. Cooper, IS., Upton, AR., Amin, I.[2019]

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]

In a study of 48 patients with chronic pain, 72% experienced complete or partial pain relief after undergoing electrical stimulation of the brain, demonstrating its efficacy as a treatment option.

The procedure was found to be safe, with no reported mortality or permanent complications, and 59% of patients were able to stop using narcotics, indicating a significant improvement in their quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrical stimulation of the brain in treatment of chronic pain. Experience over 5 years. Young, RF., Kroening, R., Fulton, W., et al.[2011]

Motor cortex stimulation (MCS) has been shown to effectively relieve deafferentation pain in 40-64% of patients, although its effectiveness may decrease over time, which can be managed by adjusting stimulation settings.

Recent advancements in non-invasive techniques like repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are providing new alternatives for pain management and helping to identify patients who are likely to respond to MCS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Motor Cortex Stimulation for Deafferentation Pain. Hussein, AE., Esfahani, DR., Moisak, GI., et al.[2018]

Citations

1. withpower.com withpower.com/trial/phase-neuralgia-9-2019-33abb

Deep Brain Stimulation for Chronic Pain This trial tests a new type of brain stimulation device for people with chronic pain that doesn't respond to other treatments. The device sends electrical ...

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

Practical Closed-Loop Strategies for Deep Brain Stimulation Here, we focus on our experiences with 3 patients implanted with the Activa PC+S (NCT03029884) and 3 patients implanted with the Summit RC+S ( ...

3. medtronic.com medtronic.com/content/dam/medtronic-wide/public/united-states/products/neurological/deep-brain-stimulation/brainsense-compendium-white-paper.pdf

BrainSense™ Technology Scientific Compendium The Percept™ PC and Percept™ RC neurostimulators with BrainSense™ technology capture brain signals (LFPs) using an implanted deep brain stimulation (DBS) lead(s) ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8959612/

Past, Present, and Future of Deep Brain Stimulation The Medtronic Percept PC received FDA approval in 2020 and is currently the only DBS IPG system capable of sensing chronic in vivo brain activity (36).

5. medtronic.com medtronic.com/content/dam/medtronic-wide/public/united-states/products/neurological/product-performance-report-deep-brain-stimulation.pdf

product-performance-report-deep-brain-stimulation. ... In the 104 neurostimulator events, 97.1 % (101/104) were assigned as device related by the physician, not returned to Medtronic RPA (see Table ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8434942/

Long-term wireless streaming of neural recordings for circuit ... Here we report a human study with an investigational second-generation bidirectional interface, Summit RC+S (Medtronic), which solves many of these limitations.

7. medtronic.com medtronic.com/me-en/healthcare-professionals/products/neurological/deep-brain-stimulation-systems/percept-pc.html

Deep Brain Stimulation Systems - Percept™ PC The Percept™ PC neurostimulator with BrainSense™ technology* is designed to capture a patient's brain signals, providing clinicians objective data directly from ...

8. frontiersin.org frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2022.1084782/full

Proceedings of the 10th annual deep brain stimulation ... In parallel, there are nearly a dozen ongoing trials evaluating the safety and effectiveness of LFP-beta controlled adaptive DBS (aDBS) in PD using the Summit™ ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9933515/

Proceedings of the 10th annual deep brain stimulation think tank In parallel, there are nearly a dozen ongoing trials evaluating the safety and effectiveness of LFP-beta controlled adaptive DBS (aDBS) in PD using the Summit™ ...