Deep Brain Stimulation for Opioid Addiction

Overseen By Jennifer Marton, BA

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: West Virginia University

Disqualifiers: Schizophrenia, Bipolar, Untreated depression, 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: 5

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if Deep Brain Stimulation (DBS), which uses electrical impulses to influence brain activity, can safely assist individuals with severe opioid addiction who have not responded to other treatments. It will specifically assess the effectiveness of DBS for those with opioid use disorder (OUD) that leads to significant cognitive and behavioral challenges. The study includes two groups: one receiving active DBS and another receiving a sham (inactive) treatment for comparison. Ideal candidates have struggled with severe OUD for over five years, experienced at least one overdose, and found no relief from other treatments. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that may lead to new treatment options for severe OUD.

Will I have to stop taking my current medications?

The trial protocol 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 addiction?

Research has shown that Deep Brain Stimulation (DBS), which targets specific brain areas, is generally safe and well-tolerated for people with opioid addiction who haven't succeeded with other treatments. In past studies, DBS reduced drug use, cravings, and emotional issues in these individuals. These studies also indicate that the procedure is feasible and doesn't cause major negative effects. Participants experienced significant improvements; one study reported an average improvement of nearly 60% in measures related to substance use disorder. Although some concerns exist about possible side effects from the electrical stimulation, current evidence suggests that DBS is a promising option for those struggling with opioid addiction. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about deep brain stimulation (DBS) for opioid addiction because it offers a unique approach compared to traditional treatments like medication-assisted therapies (e.g., methadone, buprenorphine) and behavioral therapies. Unlike these standard options, DBS targets the brain's reward and motivation circuits directly by delivering electrical impulses to specific areas, potentially reducing cravings and withdrawal symptoms more effectively. This method could provide a new avenue for individuals who haven't responded well to existing treatments, offering hope for better outcomes in managing addiction.

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

This trial will compare the effects of Deep Brain Stimulation (DBS) in two conditions: "DBS-ON" and "DBS-OFF." Research has shown that DBS can significantly aid individuals with substance use problems. Specifically, for those with opioid addiction, DBS has lowered cravings and reduced opioid use. In some cases, patients experienced an average improvement of nearly 60% in addiction symptoms. DBS also helped some patients remain off opioids longer, with durations extending from a few days to almost six months over two years. Overall, these studies suggest that DBS may offer significant relief for individuals with severe opioid addiction. ^{2 4 5 6 7}

Who Is on the Research Team?

James Mahoney, PhD

Principal Investigator

WVU Rockefeller Neuroscience Institute

Are You a Good Fit for This Trial?

This trial is for adults aged 22-50 with severe opioid use disorder (OUD) that hasn't improved after five years of trying other treatments. They must have survived an overdose and can have other substance use disorders, but OUD should be their main issue.

Inclusion Criteria

I am between 22 and 50 years old.

Fulfills current DSM-5 diagnostic criteria for severe OUD with at least a 5-year history

Participants may have comorbid SUD diagnoses at a mild, moderate or severe level, however, OUD must be the primary disorder for which the individual is seeking treatment and the other use disorders must occur in the context of relapse

Exclusion Criteria

Unable to undergo MR-imaging

I had a heart attack or cardiac arrest in the last 6 months.

I have been diagnosed with schizophrenia, bipolar disorder, or severe depression.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive Deep Brain Stimulation (DBS) or sham treatment for opioid use disorder

12 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Visits at weeks 4, 8, and 12 (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Deep Brain Stimulation

Trial Overview The study is testing Deep Brain Stimulation (DBS) on two brain areas: the nucleus accumbens and ventral internal capsule. It aims to see if DBS is safe, tolerable, and could work as a new treatment for people whose OUD doesn't respond to existing therapies.

How Is the Trial Designed?

Group I: DBS-ON Experimental Treatment 1 Intervention

Titration will be based on stimulation parameters used in previous studies examining the role of DBS of the NAc in the treatment o OCD and depression as well as the parameters utilized in the initial pilot study conducted by the team.

Group II: DBS-OFF Placebo Group 1 Intervention

For participants randomized to the "DBS-OFF" condition, titration sessions will be conducted identically to the "DBS-ON" arm, the only difference is that no stimulation is delivered and therefore, no actual adjustments made

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+

Published Research Related to This Trial

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]

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 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/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]

A systematic review of 96 studies found that the most common complications from Deep Brain Stimulation (DBS) procedures include infections (5.12% of patients) and lead migration (1.60%), highlighting the importance of monitoring for these issues post-surgery.

Patients with conditions like dystonia and off-label indications such as Tourette's syndrome are at a higher risk for hardware-related complications, suggesting that these patients should receive thorough pre-surgical counseling and close follow-up care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review of hardware-related complications of Deep Brain Stimulation: Do new indications pose an increased risk? Jitkritsadakul, O., Bhidayasiri, R., Kalia, SK., 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. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0361923022001599

Review Deep brain stimulation for opioid use disorder DBS administration effectively reduced opioid craving and consumption in human and animal subjects dependent on opioids.

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

Deep Brain Stimulation for Substance Use Disorders For treatment-refractory addictions DBS use seems limited to reducing cravings with a satisfactory degree of success, yet not clinically ...

4. medwave.io medwave.io/2024/02/deep-brain-stimulation-dbs-for-severe-opioid-addiction/

Deep Brain Stimulation (DBS) for Severe Opioid Addiction Cravings decreased, and median time abstinent increased from 0.08 to 0.50 years over 24 months. A 2020 case series following 5 patients with ...

5. 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 ...

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.