Deep Brain Stimulation for Methamphetamine Addiction

Overseen By Kristen M Raymond, BA

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Colorado, Denver

Disqualifiers: Psychotic disorders, Schizophrenia, Neurological disorder, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach to treating Methamphetamine Use Disorder (MUD) using deep brain stimulation (DBS). DBS sends electrical impulses to the nucleus accumbens in the brain, aiming to reduce cravings and use. The study will determine if this method is safe and effective for individuals who haven't succeeded with other treatments. Ideal candidates have had MUD for at least five years, tried at least two prior treatments, and are willing to undergo a short detox period. Participants must live in Colorado and complete all follow-up requirements.

As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group. It offers participants a chance to contribute to groundbreaking advancements in MUD treatment.

Will I have to stop taking my current medications?

The trial requires that you have no changes in your current psychiatric medication regimen, or be medication-free, for at least 4 weeks before joining. This means you should not start or stop any psychiatric medications during that time.

What prior data suggests that this deep brain stimulation technique is safe for methamphetamine addiction?

Research shows that deep brain stimulation (DBS), targeting the nucleus accumbens (NAc), may help treat addiction. Some studies have found this method safe and feasible. For example, in trials with individuals who have opioid addiction, DBS reduced drug use and cravings without major safety issues.

DBS has long treated conditions like Parkinson's disease, suggesting it might also work for new uses, such as methamphetamine addiction. However, since this trial is in the early stages, the main goal is to ensure the treatment's safety for participants. While the results are promising, it's important to weigh both the potential benefits and risks, especially since this is a new application of the technology. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for methamphetamine addiction?

Most treatments for methamphetamine addiction focus on behavioral therapies and medications that address withdrawal symptoms or co-occurring mental health issues. Unlike these traditional options, deep brain stimulation (DBS) targets the brain's reward system directly by delivering electrical impulses to the bilateral nucleus accumbens (NAc), a region associated with addiction. Researchers are excited about DBS because it offers a new mechanism of action that could potentially alter the brain's circuitry involved in addictive behaviors, providing a more lasting solution. This approach might help reduce cravings and prevent relapse more effectively than current therapies.

What evidence suggests that DBS of bilateral NAc might be an effective treatment for Methamphetamine Use Disorder?

Research has shown that deep brain stimulation (DBS) might help reduce cravings for methamphetamine. In this trial, participants will receive DBS of the bilateral nucleus accumbens, targeting a brain area involved in addiction. This approach may help balance chemicals like dopamine, which affect pleasure. This method has shown promise in reducing cravings and possibly aiding in overcoming addiction. Although data remains limited, early results are encouraging, suggesting that DBS could be a helpful tool for those struggling with methamphetamine addiction. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for adults aged 22-65 in Colorado with severe Methamphetamine Use Disorder (MUD), who've used meth at least 10 days in the past month and failed two prior treatments. They must test positive for meth, complete detox/surgery prep, have stable mental health treatment if any, and be medically fit for DBS surgery.

Inclusion Criteria

Adequate English proficiency for study consent, and completion of the study instruments

Able to comply with all testing and follow-up requirements as defined by study protocol

Reside in the state of Colorado

Exclusion Criteria

Pregnancy or lack of use of effective contraception in women of childbearing age

I have been diagnosed with dementia.

Inability to have an MRI

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Detoxification

Participants undergo a 1-week detoxification process

1 week

Surgery and Residential Care

Participants undergo surgery for DBS implantation followed by 30 days of residential care

4-5 weeks

DBS Stimulation and Intensive Outpatient Program/Contingency Management (IOP/CM)

Participants begin DBS stimulation and participate in a 12-week IOP/CM program

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• DBS of bilateral NAc

Trial Overview The study tests Deep Brain Stimulation (DBS) of the nucleus accumbens to treat MUD. Participants will receive either active or sham stimulation first, then switch after six months. The goal is to assess safety, feasibility, impact on drug use/craving, and explore brain activity changes through MRI.

How Is the Trial Designed?

Group I: 2 Experimental Treatment 1 Intervention

Randomized sham-controlled crossover design - participants have baseline assessments/evaluation, 1 week detoxification, surgery, 30 days residential care, then begin DBS stimulation, 12 weeks IOP/CM and are followed for 52 weeks.

Group II: 1 Experimental Treatment 1 Intervention

Randomized sham-controlled crossover design - participants have baseline assessments/evaluation, 1 week detoxification, surgery, 30 days residential care, then begin DBS stimulation, 12 weeks IOP/CM and are followed for 52 weeks.

DBS of bilateral NAc is already approved in United States, European Union for the following indications:

Approved in United States as Deep Brain Stimulation for:

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

Approved in European Union as Deep Brain Stimulation for:

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

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

University of Nebraska

Collaborator

Trials

563

Recruited

1,147,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

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 (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]

Intermittent deep brain stimulation (DBS) of the nucleus accumbens shell in rats significantly reduced methamphetamine intake by 42% to 44% during the first two days of treatment compared to sham stimulation, indicating its potential efficacy in reducing drug consumption.

DBS also led to a 57% reduction in methamphetamine-seeking behavior after treatment, suggesting that this neuromodulation technique could be a promising approach for managing addiction, particularly when applied in a non-drug environment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent bilateral deep brain stimulation of the nucleus accumbens shell reduces intravenous methamphetamine intake and seeking in Wistar rats. Batra, V., Tran, TL., Caputo, J., et al.[2019]

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) 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]

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]

Deep brain stimulation (DBS) has been successfully used to treat movement disorders and shows potential as a therapy for psychiatric disorders like addiction, based on case reports and small studies.

Targeting the nucleus accumbens (NAcc) with DBS appears to be a promising approach for treating addiction, warranting further research to explore its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation as a therapy for alcohol addiction. Münte, TF., Heinze, HJ., Visser-Vandewalle, V.[2012]

Deep brain stimulation (DBS) targeting the nucleus accumbens (NAc) in six patients with severe alcohol use disorder (AUD) led to significant reductions in cravings, alcohol consumption, and alcohol-related compulsivity over 12 months, demonstrating its potential as a safe and effective treatment.

Improvements in compulsive drinking behaviors were linked to reduced glucose metabolism in the NAc and decreased functional connectivity between the NAc and the visual association cortex, suggesting a mechanism by which NAc-DBS may help mitigate the effects of alcohol-related cues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation of the nucleus accumbens in the treatment of severe alcohol use disorder: a phase I pilot trial. Davidson, B., Giacobbe, P., George, TP., et al.[2023]

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 shows promise as a potential treatment for severe cocaine and methamphetamine use disorders, based on both clinical and preclinical evidence.

Current research on DBS lacks diversity, particularly with a significant absence of female participants, highlighting the need for more inclusive studies to better understand its efficacy across different populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for psychostimulant use disorders. Swinford-Jackson, SE., Pierce, RC.[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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05558358

Deep Brain Stimulation (DBS) for Methamphetamine Use ... This is a small randomized cross-over study to demonstrate feasibility and safety, test treatment outcomes (use, craving), and identify novel ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9022905/

Deep Brain Stimulation in Drug Addiction Treatment It has been hypothesized that DBS may alleviate addiction symptoms through normalizing dopamine levels and restore the functioning of the reward system (2).

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03347474

Deep Brain Stimulation of Nucleus Accumbens for ... Our hypothesis is that bilateral DBS of the NAc will significantly reduce the craving for methamphetamine. Official Title. Deep Brain Stimulation of Nucleus ...

4. trialx.com trialx.com/clinical-trials/listings/223831/deep-brain-stimulation-dbs-for-methamphetamine-use-disorder/

Deep Brain Stimulation (DBS) for Methamphetamine Use Disorder This is a small randomized cross-over study to demonstrate feasibility and safety, test treatment outcomes (use, craving), and identify novel biological targets ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0024320523002473

Distinct suppressing effects of deep brain stimulation in the ... DBS administration in the OFC demonstrated some positive results, including suppressing effects on the development, maintenance, and relapse of methamphetamine ...

6. reporter.nih.gov reporter.nih.gov/project-details/10630368

Deep Brain Stimulation (DBS) For Severe Treatment ... A growing body of animal model and human clinical data suggests NAc stimulation may be beneficial in the treatment of addiction. Here we propose a two-phase ...

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.