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

4 Participants Needed

Trial Summary

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 data supports the effectiveness of this treatment for opioid use disorder?

Research shows that deep brain stimulation (DBS) can reduce opioid craving and consumption in both humans and animals. Studies targeting the nucleus accumbens, a brain area involved in reward and motivation, have shown promising results in reducing addiction-related behaviors. ^{1 2 3 4 5}

Is deep brain stimulation (DBS) generally safe for humans?

Deep brain stimulation (DBS) has been studied for various conditions, and while it can be effective, there are risks involved. Some studies report no serious adverse events, but others note surgical and hardware-related complications that can affect quality of life. It's important to weigh these risks when considering DBS. ^{6 7 8 9 10}

How is deep brain stimulation different from other treatments for opioid use disorder?

Deep brain stimulation (DBS) is unique because it involves a surgical procedure to implant electrodes in specific brain areas, like the nucleus accumbens, to reduce opioid cravings and consumption. Unlike traditional treatments that often rely on medications or therapy, DBS directly modulates brain activity to address addiction. ^{1 2 4 11 12}

What is the purpose of this trial?

The purpose of this clinical study is to investigate the safety, tolerability, and feasibility of Deep Brain Stimulation (DBS) of the nucleus accumbens (NAc) and ventral internal capsule (VC) for participants with treatment refractory opioid use disorder (OUD) who have cognitive, behavioral, and functional disability. This study will also provide critical information for planning subsequent clinical trials.

Research Team

Ali Rezai

Principal Investigator

West Virginia University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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) 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]

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]

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) 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]

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]

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]

References

1. United States 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. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation in Drug Addiction Treatment: Research Progress and Perspective. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Outcomes of deep brain stimulation surgery for substance use disorder: a systematic review. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for opioid use disorder: A systematic review of preclinical and clinical evidence. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

A Systematic Review of Noninvasive Brain Stimulation for Opioid Use Disorder. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Deep brain stimulation of the nucleus accumbens/ventral capsule for severe and intractable opioid and benzodiazepine use disorder. [2022]

7. Austria pubmed.ncbi.nlm.nih.gov

Complications of deep brain stimulation in Parkinson's disease: a single-center experience of 517 consecutive cases. [2023]

8. England 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. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Surgical and Hardware-Related Adverse Events of Deep Brain Stimulation: A Ten-Year Single-Center Experience. [2022]

10. Turkey pubmed.ncbi.nlm.nih.gov

Surgical-Related and Hardware-Related Adverse Effects of Deep Brain Stimulation: A Retrospective Single-Center Analysis. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Chronic unilateral stimulation of the nucleus accumbens at high or low frequencies attenuates relapse to cocaine seeking in an animal model. [2018]

12. United States pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation of Nucleus Accumbens for Methamphetamine Addiction: Two Case Reports. [2019]