Deep Brain Stimulation for Opioid Use Disorder

(DBS_OUD Trial)

Overseen By Barbara Harring

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: West Virginia University

Must not be taking: Anticoagulants

Disqualifiers: Schizophrenia, Bipolar, Dementia, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the use of Deep Brain Stimulation (DBS), which sends electrical impulses to specific brain areas, to help individuals with severe opioid use disorder (OUD) who have not responded to other treatments. The trial aims to determine if DBS is safe and tolerable for participants and to gather information for future studies. It targets individuals who have struggled with OUD for at least five years, survived multiple overdoses, and not benefited from previous treatments like inpatient programs or medication. Participants will initially stay in a hospital to gather baseline data and adjust the DBS, followed by regular follow-ups for a year. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new treatment options for OUD.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that Deep Brain Stimulation is safe for opioid use disorder?

Research shows that Deep Brain Stimulation (DBS) in specific brain areas is generally safe and well-tolerated for people with severe opioid use disorder (OUD). Studies have found that this method can help reduce drug use and cravings in those who haven't succeeded with other treatments. Most reports indicate that DBS doesn't cause major side effects for most patients, making it a promising option for those dealing with OUD. While some studies highlight its potential, results can vary, and ongoing research will provide more information about its safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for opioid use disorder involve medications like methadone, buprenorphine, or naltrexone, which work by interacting with opioid receptors to reduce cravings and withdrawal symptoms. However, Deep Brain Stimulation (DBS) is unique because it targets specific brain regions directly involved in addiction through electrical impulses, potentially altering brain circuits that drive addictive behaviors. Researchers are excited about DBS because it offers a novel mechanism of action that could provide an alternative for patients who do not respond well to medication-based therapies. This approach has the potential to offer a more personalized and potentially more effective treatment pathway for managing opioid addiction.

What evidence suggests that Deep Brain Stimulation is effective for opioid use disorder?

Research has shown that deep brain stimulation (DBS) can greatly help people with substance use problems. One study found that patients improved by an average of 59.6% on clinical tests after treatment. Although complete recovery rates aren't always high, DBS has shown promise in reducing cravings for those with opioid use disorder (OUD). This trial will specifically evaluate DBS for OUD, offering a potential option for people who haven't succeeded with other treatments. However, due to the complexity of OUD, treating it with DBS can be challenging. ^{3 4 5 6 7}

Who Is on the Research Team?

Ali Rezai

Principal Investigator

West Virginia University

Are You a Good Fit for This Trial?

This trial is for adults with severe opioid use disorder (OUD) who have tried multiple treatments without success, including buprenorphine/naloxone. They should have a history of at least two overdoses or one overdose and a serious infection related to drug use. Participants need social support and cannot be pregnant, have certain brain conditions, HIV, or be on anticoagulants.

Inclusion Criteria

Is able to provide informed consent

Fulfills current DSM-5 diagnostic criteria for OUD (severe) and at least a 5-year history

Failed at least two levels of treatment (outpatient/Comprehensive Opioid Addiction Treatment (COAT), intensive outpatient/intensive COAT, residential, inpatient, Adult Intensive Outpatient Program (AIOP), Dual Diagnosis Unit (DDU), which included buprenorphine/naloxone

Exclusion Criteria

Pregnant or planning to become pregnant

You have had a stroke caused by bleeding in the brain.

Any current CNS infection or infection with the Human Immunodeficiency Virus (HIV)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Inpatient service for baseline data collection

Treatment

DBS placement and clinical stabilization with DBS titration

6 weeks

Inpatient service

Outpatient Follow-up

Participants are monitored twice a week for 12 weeks post-titration

12 weeks

Twice a week visits

Long-term Follow-up

Participants are monitored once a week for a total of 52 weeks post-titration

52 weeks

Weekly visits

What Are the Treatments Tested in This Trial?

Interventions

• Deep Brain Stimulation

Trial Overview The study tests the safety and feasibility of Deep Brain Stimulation (DBS) targeting specific brain areas in people with treatment-resistant OUD. It aims to provide information for future trials by assessing how well participants tolerate DBS and its initial effectiveness.

How Is the Trial Designed?

Group I: OUD DBS Experimental Treatment 1 Intervention

This is a single arm study. Participants will be followed in an inpatient service for two weeks to gather baseline data followed by DBS placement and up to 6 weeks inpatient for clinical stabilization and DBS titration. All participants will then be followed twice a week for 12 weeks in the outpatient setting and then once a week for a total of 52 weeks post-titration.

Deep Brain Stimulation is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Deep Brain Stimulation for:

• Essential tremor
• Parkinson's disease
• Dystonia
• Obsessive-compulsive disorder
• Epilepsy
• Chronic pain
• Stroke-related motor deficits (under investigation)

Approved in European Union as Deep Brain Stimulation for:

• Essential tremor
• Parkinson's disease
• Dystonia
• Obsessive-compulsive disorder
• Epilepsy
• Chronic pain

Approved in Canada as Deep Brain Stimulation for:

• Essential tremor
• Parkinson's disease
• Dystonia
• Obsessive-compulsive disorder
• Epilepsy
• Chronic pain

Who Is Running the Clinical Trial?

West Virginia University

Lead Sponsor

Trials

192

Recruited

64,700+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Medtronic

Industry Sponsor

Trials

627

Recruited

767,000+

Geoff Martha

Medtronic

Chief Executive Officer since 2020

Finance degree from Penn State University

Dr. Richard Kuntz

Medtronic

Chief Medical Officer since 2023

MD, MSc

Published Research Related to This Trial

Deep brain stimulation of the NAcore region significantly reduced cue-induced reinstatement of heroin seeking and decreased motivation for heroin taking, suggesting its potential as a treatment for substance use dependence.

In contrast, stimulation of the NAshell region did not affect heroin seeking or self-administration, highlighting the distinct roles of these brain sub-regions in addiction behavior.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation of the nucleus accumbens core but not shell reduces motivational components of heroin taking and seeking in rats. Schippers, MC., Gaastra, M., Mesman, T., et al.[2022]

Deep brain stimulation (DBS) for Parkinson's disease is generally safe, with a low mortality rate of 0.2% and permanent morbidity at 0.6%, but complications such as intracerebral hemorrhage (ICH) and seizures can occur in a small percentage of cases.

The study found that the type of lead used in DBS can influence complications, with Medtronic's leads associated with higher rates of perielectrode brain edema compared to Boston Scientific's, highlighting the need for further research on hardware design to improve safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications of deep brain stimulation in Parkinson's disease: a single-center experience of 517 consecutive cases. Servello, D., Galbiati, TF., Iess, G., et al.[2023]

This study will evaluate the safety and efficacy of deep brain stimulation (DBS) targeting the nucleus accumbens and anterior limb of the internal capsule in 60 patients with refractory opioid dependence over a 25-week follow-up period.

The primary outcome will be the abstinence rate confirmed by urine tests, while secondary outcomes will assess changes in craving, psychological health, and overall well-being, providing a comprehensive view of DBS's impact on opioid addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical evaluation of deep brain stimulation of nucleus accumbens/anterior limb of internal capsule for opioid relapse prevention: protocol of a multicentre, prospective and double-blinded study. Qu, L., Ge, S., Li, N., et al.[2020]

In a study of 200 patients undergoing deep brain stimulation (DBS) procedures over a follow-up period of approximately 43 months, 20% experienced surgical or hardware-related adverse events (AEs), but all resolved without permanent effects.

The most common AEs were surgical site infections (9.95%) and wire tethering (2.49%), indicating that while AEs can occur, major complications requiring further surgery are rare, highlighting the overall safety of DBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical and Hardware-Related Adverse Events of Deep Brain Stimulation: A Ten-Year Single-Center Experience. Bouwens van der Vlis, TAM., van de Veerdonk, MMGH., Ackermans, L., et al.[2022]

Deep brain stimulation (DBS) targeting the Nucleus Accumbens/Ventral anterior internal capsule was found to be safe for a participant with severe treatment refractory opioid and benzodiazepine use disorders, with no serious adverse events reported over a 12-month follow-up.

DBS significantly reduced substance cravings, particularly for benzodiazepines, and showed trends toward improved executive functions and heart rate variability, suggesting potential benefits for treating substance use disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation of the nucleus accumbens/ventral capsule for severe and intractable opioid and benzodiazepine use disorder. Mahoney, JJ., Haut, MW., Hodder, SL., et al.[2022]

Deep Brain Stimulation (DBS) targeting the nucleus accumbens (NAc) shows promising treatment effects for drug addiction, which is linked to neuroplastic changes in this brain region.

The review summarizes clinical trial results indicating that DBS may be effective for addiction to various substances, including nicotine, alcohol, cocaine, opioids, and methamphetamine, suggesting its potential as a novel treatment option for substance abuse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation in Drug Addiction Treatment: Research Progress and Perspective. Chang, R., Peng, J., Chen, Y., et al.[2022]

Deep brain stimulation (DBS) of the nucleus accumbens (NAc) may be a potential treatment for methamphetamine addiction, as shown in a case study of two patients over a 2-year follow-up period.

One patient experienced successful abstinence and positive emotional changes, while the other did not show significant improvement and relapsed, highlighting the importance of accurate electrode placement for effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation of Nucleus Accumbens for Methamphetamine Addiction: Two Case Reports. Ge, S., Chen, Y., Li, N., et al.[2019]

In a study of 47 patients who underwent deep brain stimulation (DBS) surgery, 70.2% experienced no adverse effects, indicating a generally favorable safety profile for this treatment.

However, the study identified that 19.1% of patients had hardware-related complications, including infections and lead malposition, highlighting the need for careful monitoring and management of these risks post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical-Related and Hardware-Related Adverse Effects of Deep Brain Stimulation: A Retrospective Single-Center Analysis. Erdem, NS., Ozkaynak, SS., Cakin, H., et al.[2022]

Noninvasive brain stimulation (NIBS) shows potential as a novel treatment strategy for opioid use disorder (OUD), but current research is limited, with only five studies involving a total of 150 participants identified in a systematic review.

The studies utilized various NIBS techniques, including TMS and tDCS, to target issues like cue-induced craving and withdrawal symptoms, indicating that while promising, more extensive research is needed to fully understand the efficacy and mechanisms of NIBS in treating OUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review of Noninvasive Brain Stimulation for Opioid Use Disorder. Ward, HB., Mosquera, MJ., Suzuki, J., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10449586/

Deep brain stimulation for substance use disorder The results showed that DBS treatment resulted in a significant improvement in the clinical SUD scales of patients, with an average improvement of 59.6%.

2. nature.com nature.com/articles/s41398-024-03060-1

A systematic review of deep brain stimulation for substance ... Clinical studies suggest that DBS as a therapeutic option for treatment-refractory SUDs has not yielded high enough remission rates that would ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03950492

Feasibility of Deep Brain Stimulation as a Novel Treatment ... The purpose of this clinical study is to investigate the safety, tolerability, and feasibility of Deep Brain Stimulation (DBS) of the nucleus accumbens (NAc) ...

4. ojphi.jmir.org ojphi.jmir.org/2024/1/e49924/

Public Perceptions of Treating Opioid Use Disorder With Deep ... Using DBS as a treatment method for OUD was described as potentially treating one problem by creating another problem, electrical stimulation ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1094715922009424

O130 / #985 NUCLEUS ACCUMBENS DEEP BRAIN ... DBS for OUD is promising but challenging given the complex nature of the population and disease. All active participants experienced reductions in craving, ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37329519/

Safety and feasibility clinical trial of nucleus accumbens deep ... DBS of the NAc/VC was safe, feasible, and can potentially reduce substance use, craving, and emotional symptoms in those with treatment-refractory OUD.

7. thejns.org thejns.org/view/journals/j-neurosurg/140/1/article-p231.xml

Safety and feasibility clinical trial of nucleus accumbens deep ... DBS of the NAc/VC was safe, feasible, and can potentially reduce substance use, craving, and emotional symptoms in those with treatment-refractory OUD.