Deep Brain Stimulation for Opioid Use Disorder

Overseen by Nestor Tomycz, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)

Must be taking: Methadone, Buprenorphine, Suboxone

Must not be taking: Anticoagulants, Antiplatelets

Disqualifiers: Prior brain surgery, Seizures, Dementia, Pregnancy, others

Stay on Your Current Meds

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests a brain device that sends electrical signals to help people with severe opioid addiction who don't respond to usual treatments. The device aims to reduce cravings and prevent relapse by targeting a specific brain area involved in addiction.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should not have active illicit substance abuse and must be part of a medication-assisted treatment program, which may include methadone or buprenorphine.

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

Research suggests that deep brain stimulation (DBS) of the nucleus accumbens (NAc) may help reduce addictive behaviors, as seen in animal studies where it decreased addiction to substances like alcohol and cocaine. Additionally, some small clinical studies have shown promising results in humans, but larger studies are needed to confirm its effectiveness for opioid use disorder. ^{1 2 3 4 5}

Is deep brain stimulation of the nucleus accumbens safe for humans?

Deep brain stimulation (DBS) of the nucleus accumbens has been studied for various conditions, including addiction and psychiatric disorders. In a study involving a person with severe opioid and benzodiazepine use disorders, DBS was found to be safe with no serious side effects. Additionally, animal studies and initial human trials suggest that DBS of this brain area is generally safe. ^{1 2 6 7 8}

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

Deep brain stimulation (DBS) is unique because it involves surgically implanting electrodes in the brain to modulate neural activity, specifically targeting the nucleus accumbens, a key area involved in addiction. Unlike traditional treatments like medication or therapy, DBS is reversible, adjustable, and minimally invasive, offering a novel approach for those with treatment-resistant opioid dependence. ^{1 2 3 4 5}

Research Team

Nestor Tomycz, MD

Principal Investigator

Allegheny Health Network

Eligibility Criteria

This trial is for adults over 22 with a primary diagnosis of opioid use disorder (OUD) based on DSM-V, who have struggled with OUD for at least 5 years and failed multiple treatments. Participants must not have severe psychiatric disorders or other substance abuse issues, should be in good physical health without serious infections or blood clotting problems, and cannot be pregnant.

Inclusion Criteria

Has completed a neuro-psychological evaluation to the satisfaction of a neuropsychologist

OUD must be the primary disorder

Negative blood cultures to rule out bacteremia

Exclusion Criteria

I have severe brain shrinkage or fluid/blood under my skull's lining.

I have signs of heart valve infection.

Have any other medical condition that, in the opinion of the Investigator, makes the subject unsuitable for enrollment

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Initial Recovery

Participants undergo DBS brain electrode implantation and are admitted post-operatively for an overnight stay

1 week

1 visit (in-person, surgical)

Post-Surgery Programming and Adjustment

Two weeks after surgery, subjects undergo systematic testing and programming of DBS settings

2 weeks

Multiple visits (in-person)

Treatment

Participants receive ongoing DBS treatment with routine outpatient visits for parameter adjustments

24 months

Routine outpatient visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Treatment Details

Interventions

• DBS of the NAc (Device)

Trial Overview The study tests deep brain stimulation (DBS) of the nucleus accumbens (NAc) as an additional treatment for those with hard-to-treat opioid addiction. It will include only three individuals who continue to relapse despite being in a drug treatment program.

Participant Groups

Group I: NAc DBS Experimental Treatment 1 Intervention

Subjects will receive bilateral DBS of the NAc

Who Is Running the Clinical Trial?

Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)

Lead Sponsor

Trials

52

Recruited

13,000+

Abbott

Industry Sponsor

Trials

760

Recruited

489,000+

Dr. Etahn Korngold

Abbott

Chief Medical Officer

MD, Harvard Medical School

Robert B. Ford

Abbott

Chief Executive Officer since 2020

Bachelor's degree from Boston College, MBA from UC Berkeley, Haas School of Business

Findings from Research

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 (NA) shows promise in reducing addictive behaviors related to substances like alcohol and cocaine, supported by both animal studies and preliminary human observations.

While initial results from small patient series indicate potential benefits of DBS for addiction, larger, well-structured studies are necessary to establish its efficacy and safety as a standard treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nucleus Accumbens as a Novel Target for Deep Brain Stimulation in the Treatment of Addiction: A Hypothesis on the Neurochemical and Morphological Basis. Vannemreddy, P., Slavin, K.[2020]

High-frequency stimulation (HFS) at 120 Hz in the nucleus accumbens during the extinction phase of morphine addiction increased conditioned place preference (CPP) scores, indicating a temporary enhancement of addictive behavior.

In contrast, HFS applied during the postextinction phase significantly reduced relapse CPP scores, suggesting that this timing of stimulation can effectively suppress drug-seeking behavior after withdrawal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of High-Frequency Electrical Stimulation of Bilateral Nucleus Accumbens on the Behavior of Morphine-Induced Conditioned Place Preference Rats at Extinction and Reinstatement Phases. Yang, C., Qiu, Y., Hu, X., et al.[2022]

Deep brain stimulation (DBS) targeting the nucleus accumbens (NAc) shows promise as a treatment for patients with treatment-refractory addiction, based on a review of 14 human studies.

The safety profile of DBS in addiction treatment is generally good, suggesting it could be a viable option for patients with severe addiction issues, particularly for those addicted to substances like heroin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nucleus accumbens as a stereotactic target for the treatment of addictions in humans: a literature review. Sobstyl, M., Kupryjaniuk, A., Mierzejewski, P.[2021]

High-frequency deep brain stimulation (DBS) in the nucleus accumbens (NAc) effectively prevented the reinstatement of morphine-seeking behavior in morphine-dependent rats, suggesting its potential as a treatment for opiate addiction.

The study demonstrated that DBS accelerated the natural decline of drug craving without negatively impacting learning and memory, indicating a promising therapeutic approach for severe morphine addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of the reinstatement of morphine-induced place preference in rats by high-frequency stimulation of the bilateral nucleus accumbens. Ma, Y., Chen, N., Wang, HM., et al.[2013]

Deep brain stimulation (DBS) targeting the nucleus accumbens (NAc) shows promise in reducing alcohol cravings and achieving long-term abstinence in individuals with alcohol use disorder (AUD), supported by both animal and initial human studies.

The review highlights the NAc as a key area in AUD treatment and discusses the potential of DBS as a neuromodulation strategy, while also addressing challenges and future directions for research in this field.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The nucleus accumbens and alcoholism: a target for deep brain stimulation. Ho, AL., Salib, AN., Pendharkar, AV., et al.[2021]

This study is the first to report on deep brain stimulation (DBS) of the nucleus accumbens (NAc) in nonhuman primates, indicating its potential as a target for treating psychiatric disorders.

The bilateral electrical stimulation of the NAc was found to be safe, with no significant changes in behavior or locomotor activity observed during the stimulation period, suggesting that this model could aid in future research on NAc stimulation's clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation of the bilateral nucleus accumbens in normal rhesus monkey. Li, N., Gao, L., Wang, XL., et al.[2012]

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]

References

1. 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]

2. India pubmed.ncbi.nlm.nih.gov

Nucleus Accumbens as a Novel Target for Deep Brain Stimulation in the Treatment of Addiction: A Hypothesis on the Neurochemical and Morphological Basis. [2020]

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

The Effect of High-Frequency Electrical Stimulation of Bilateral Nucleus Accumbens on the Behavior of Morphine-Induced Conditioned Place Preference Rats at Extinction and Reinstatement Phases. [2022]

4. Poland pubmed.ncbi.nlm.nih.gov

Nucleus accumbens as a stereotactic target for the treatment of addictions in humans: a literature review. [2021]

5. China pubmed.ncbi.nlm.nih.gov

Inhibition of the reinstatement of morphine-induced place preference in rats by high-frequency stimulation of the bilateral nucleus accumbens. [2013]

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

The nucleus accumbens and alcoholism: a target for deep brain stimulation. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Deep brain stimulation of the bilateral nucleus accumbens in normal rhesus monkey. [2012]

8. 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]