Deep Brain Stimulation for Methamphetamine Addiction

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: University of Colorado, Denver

Disqualifiers: Psychotic disorders, Schizophrenia, Neurological disorder, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

We will evaluate the effects of deep brain stimulation (DBS) of bilateral nucleus accumbens (NAc) added to background treatment for treatment refractory Methamphetamine Use Disorder (MUD). This is a small randomized cross-over study to demonstrate feasibility and safety, test treatment outcomes (use, craving), and identify novel biological targets (NAc local field potentials (LFP) and functional MRI).

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 data supports the effectiveness of this treatment for methamphetamine addiction?

Deep brain stimulation (DBS) of the nucleus accumbens (NAc) has shown promise in treating addiction, with studies indicating it can reduce addictive behaviors in animals and provide relief from addiction in some human cases. Although more research is needed, DBS has been effective for other addictions like alcohol and nicotine, suggesting potential benefits for methamphetamine addiction as well. ^{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 substance use disorders, including opioid, benzodiazepine, and alcohol use disorders, and has generally been found to be safe with no serious adverse events reported in these studies. Additionally, studies in nonhuman primates have shown that DBS of the nucleus accumbens is safe, suggesting it could be a safe treatment option for humans. ^{3 6 7 8 9}

How is deep brain stimulation different from other treatments for methamphetamine addiction?

Deep brain stimulation (DBS) for methamphetamine addiction is unique because it involves implanting electrodes in the brain to modulate activity in the nucleus accumbens, a key area involved in addiction, rather than using medications or behavioral therapies. This approach is still being researched and is not yet a standard treatment, but it shows promise for reducing drug intake and seeking behavior. ^{1 3 5 10 11}

Research Team

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• DBS of bilateral NAc (Device)

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.

Participant Groups

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.

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Aviva Abosch

University of Colorado, Denver

Chief Medical Officer since 2019

MD

Uday B. Kompella

University of Colorado, Denver

Chief Executive Officer since 2015

PhD in Pharmaceutical Sciences

University of Nebraska

Collaborator

Trials

563

Recruited

1,147,000+

Michael Dixon

University of Nebraska

Chief Executive Officer since 2010

PhD in Molecular Biology

Dr. Makker

University of Nebraska

Chief Medical Officer since 2020

MD from University of Nebraska Medical School

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Dr. Nora Volkow

National Institute on Drug Abuse (NIDA)

Chief Executive Officer since 2003

MD from National Autonomous University of Mexico

Dr. Nora Volkow

National Institute on Drug Abuse (NIDA)

Chief Medical Officer since 2003

MD from National Autonomous University of Mexico

Findings from Research

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) 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]

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]

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) 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) 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]

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) 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. Germany pubmed.ncbi.nlm.nih.gov

Deep brain stimulation as a therapy for alcohol addiction. [2012]

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

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

3. Austria pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for psychostimulant use disorders. [2023]

4. 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]

5. Poland pubmed.ncbi.nlm.nih.gov

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

6. 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]

7. 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]

8. England 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. [2023]

9. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

Intermittent bilateral deep brain stimulation of the nucleus accumbens shell reduces intravenous methamphetamine intake and seeking in Wistar rats. [2019]