Deep Brain Stimulation to Understand and Treat Addiction

NCT ID: NCT07341230

Last Updated: 2026-01-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

9 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-07-01

Study Completion Date

2027-10-31

Brief Summary

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This study is testing whether deep brain stimulation (DBS) can safely help people with severe alcohol use disorder who have not improved with standard treatments. DBS uses small electrical signals to change activity in brain areas linked to craving, self-control, and emotion. The study will test whether this treatment can reduce how often people drink and how much they drink each day. Researchers will also record brain activity to better understand how DBS affects craving and relapse.

Detailed Description

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Alcohol use disorder (AUD) is a leading cause of preventable illness and death worldwide and remains a major public health concern. In the United Kingdom, alcohol misuse is the greatest risk factor for death and disability among adults aged 15-49, yet many people relapse despite standard treatments. Treatment-refractory AUD therefore represents an urgent unmet clinical need. Addiction is increasingly viewed as a disorder of maladaptive brain network activity involving dysregulation of motivation, reward, stress, and executive-control systems.

Deep brain stimulation (DBS) delivers small electrical pulses to targeted brain areas to restore balanced network activity. DBS is established for movement and obsessive-compulsive disorders, and early studies suggest potential benefit for substance addictions.

This pilot trial tests dual-target DBS of the nucleus accumbens and ventral internal capsule to modulate circuits supporting craving, emotion, and self-control. Participants with severe, treatment-resistant AUD will undergo an initial open-label optimization phase followed by a randomized, blinded cross-over comparison of dual, single-site, and sham stimulation. Primary outcomes are changes in drinking frequency and quantity. Intracranial recordings from the implanted device will capture local field potentials to identify brain-signal patterns linked to craving and emotion, helping guide the development of future adaptive neuromodulation approaches for addiction.

Conditions

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Alcohol Use Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

This study uses a multiphase design consisting of an initial open-label optimization phase followed by a randomized, double-blind, 4-arm crossover trial.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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Dual Stimulation (Nucleus Accumbens + Ventral Internal Capsule)

Participants receive active deep brain stimulation simultaneously targeting both the nucleus accumbens and the ventral internal capsule.

Group Type EXPERIMENTAL

Dual-Target Deep Brain Stimulation

Intervention Type DEVICE

A surgically implanted deep brain stimulation (DBS) system delivers active stimulation simultaneously to the nucleus accumbens and the ventral internal capsule. Stimulation parameters are based on individualized optimization performed prior to randomization and remain constant throughout this condition.

Single Stimulation - Nucleus Accumbens Only

Participants receive active deep brain stimulation targeting the nucleus accumbens only, with ventral internal capsule stimulation inactive.

Group Type ACTIVE_COMPARATOR

Nucleus Accumbens Deep Brain Stimulation

Intervention Type DEVICE

A surgically implanted deep brain stimulation (DBS) system delivers active stimulation to the nucleus accumbens only. Ventral internal capsule stimulation is inactive. Stimulation parameters are based on individualized optimization performed prior to randomization and remain constant throughout this condition.

Single Stimulation - Ventral Internal Capsule Only

Participants receive active deep brain stimulation targeting the ventral internal capsule only, with nucleus accumbens stimulation inactive.

Group Type ACTIVE_COMPARATOR

Ventral Internal Capsule Deep Brain Stimulation

Intervention Type DEVICE

A surgically implanted deep brain stimulation (DBS) system delivers active stimulation to the ventral internal capsule only. Nucleus accumbens stimulation is inactive. Stimulation parameters are based on individualized optimization performed prior to randomization and remain constant throughout this condition.

Sham Stimulation (Inactive)

Participants receive sham (inactive) deep brain stimulation. The implanted device is turned off; no therapeutic stimulation is provided.

Group Type SHAM_COMPARATOR

Sham Deep Brain Stimulation

Intervention Type DEVICE

A surgically implanted deep brain stimulation (DBS) system is present but no therapeutic stimulation is delivered during this condition. All stimulation remains inactive.

Interventions

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Dual-Target Deep Brain Stimulation

A surgically implanted deep brain stimulation (DBS) system delivers active stimulation simultaneously to the nucleus accumbens and the ventral internal capsule. Stimulation parameters are based on individualized optimization performed prior to randomization and remain constant throughout this condition.

Intervention Type DEVICE

Nucleus Accumbens Deep Brain Stimulation

A surgically implanted deep brain stimulation (DBS) system delivers active stimulation to the nucleus accumbens only. Ventral internal capsule stimulation is inactive. Stimulation parameters are based on individualized optimization performed prior to randomization and remain constant throughout this condition.

Intervention Type DEVICE

Ventral Internal Capsule Deep Brain Stimulation

A surgically implanted deep brain stimulation (DBS) system delivers active stimulation to the ventral internal capsule only. Nucleus accumbens stimulation is inactive. Stimulation parameters are based on individualized optimization performed prior to randomization and remain constant throughout this condition.

Intervention Type DEVICE

Sham Deep Brain Stimulation

A surgically implanted deep brain stimulation (DBS) system is present but no therapeutic stimulation is delivered during this condition. All stimulation remains inactive.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* Adults aged 18 to 60 years
* Diagnosed with Alcohol Use Disorder (AUD) according to DSM-5 criteria
* Primary diagnosis of treatment-refractory AUD (comorbid nicotine dependence, other psychoactive substance use disorders, moderate major depressive disorder, anxiety disorders or obsessive-compulsive disorder are permissible if AUD is principal)
* Disorder duration of AUD ≥ 5 years
* At least 3 unsuccessful attempts at achieving abstinence
* Failed prior psychotherapy and standard pharmacotherapy for AUD
* Medically and neurologically suitable for surgery and MRI-compatible
* Capable of providing informed consent and willing to comply with study procedures

Exclusion Criteria

* Severe psychiatric disorder other than Alcohol Use Disorder (e.g., schizophrenia, schizoaffective disorder, bipolar disorder)
* Severe major depressive disorder (moderate depression acceptable)
* Current active suicidal ideation or history of serious suicide attempts
* Previous treatment with electroconvulsive therapy (ECT)
* Presence of implanted electrical devices, including:
* Cardiac pacemaker or defibrillator (or clinical indication for pacemaker placement)
* Implanted vagus nerve stimulator (VNS)
* Any other chronically implanted neurostimulation device
* Significant neurological history, including prior hemorrhagic or ischemic stroke, subarachnoid hemorrhage, or other major neurological illness
* Any significant medical condition that, in the opinion of the clinical team, would increase surgical or anesthetic risk
* Current pregnancy
* Contraindications to deep brain stimulation or neurosurgery, including:
* Inability to tolerate general anesthesia (as assessed by anesthesiology)
* Increased risk of bleeding (as determined by hepatology/hematology review)
* History of coagulopathy
* Current or previous anticoagulant use
* Uncontrolled hypertension (controlled hypertension with medication is acceptable)
* Stage 4 liver cirrhosis
* History of major cardiac arrhythmia (e.g., atrial fibrillation) or need for anti-arrhythmic medication
* History of requiring cardioversion
* History of repeated falls
* History of major head injury
* Marked cognitive impairment
* Seizure history, including multiple alcohol withdrawal seizures
* Marked cortical atrophy on neuroimaging
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cambridge University Hospitals NHS Foundation Trust

OTHER

Sponsor Role collaborator

King's College Hospital NHS Trust

OTHER

Sponsor Role collaborator

University of Cambridge

OTHER

Sponsor Role lead

Responsible Party

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Valerie Voon

Professor Valerie Voon, Professor of Neuropsychiatry and Neuromodulation, Department of Psychiatry, University of Cambridge

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Cambridge University Hospitals (Addenbrooke's Hospital)

Cambridge, Cambridgeshire, United Kingdom

Site Status RECRUITING

King's College Hospital

London, Greater London, United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Facility Contacts

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Samantha N Sallie, PhD

Role: primary

01223 245151

Peter Kosa, MBBS

Role: primary

02032999000

References

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Rezai AR, Mahoney JJ, Ranjan M, Haut MW, Zheng W, Lander LR, Berry JH, Farmer DL, Marton JL, Tirumalai P, Mears A, Thompson-Lake DGY, Finomore VS, D'Haese PF, Aklin WM, George DT, Corrigan JD, Hodder SL. Safety and feasibility clinical trial of nucleus accumbens deep brain stimulation for treatment-refractory opioid use disorder. J Neurosurg. 2023 Jun 9;140(1):231-239. doi: 10.3171/2023.4.JNS23114. Print 2024 Jan 1.

Reference Type RESULT
PMID: 37329519 (View on PubMed)

Davidson B, Giacobbe P, George TP, Nestor SM, Rabin JS, Goubran M, Nyman AJ, Baskaran A, Meng Y, Pople CB, Graham SJ, Tam F, Hamani C, Lipsman N. Deep brain stimulation of the nucleus accumbens in the treatment of severe alcohol use disorder: a phase I pilot trial. Mol Psychiatry. 2022 Oct;27(10):3992-4000. doi: 10.1038/s41380-022-01677-6. Epub 2022 Jul 21.

Reference Type RESULT
PMID: 35858989 (View on PubMed)

Bach P, Luderer M, Muller UJ, Jakobs M, Baldermann JC, Voges J, Kiening K, Lux A, Visser-Vandewalle V; DeBraSTRA study group; Bogerts B, Kuhn J, Mann K. Deep brain stimulation of the nucleus accumbens in treatment-resistant alcohol use disorder: a double-blind randomized controlled multi-center trial. Transl Psychiatry. 2023 Feb 8;13(1):49. doi: 10.1038/s41398-023-02337-1.

Reference Type RESULT
PMID: 36755017 (View on PubMed)

Chen L, Li N, Ge S, Lozano AM, Lee DJ, Yang C, Li L, Bai Q, Lu H, Wang J, Wang X, Li J, Jing J, Su M, Wei L, Wang X, Gao G. Long-term results after deep brain stimulation of nucleus accumbens and the anterior limb of the internal capsule for preventing heroin relapse: An open-label pilot study. Brain Stimul. 2019 Jan-Feb;12(1):175-183. doi: 10.1016/j.brs.2018.09.006. Epub 2018 Sep 14.

Reference Type RESULT
PMID: 30245163 (View on PubMed)

Muller UJ, Voges J, Steiner J, Galazky I, Heinze HJ, Moller M, Pisapia J, Halpern C, Caplan A, Bogerts B, Kuhn J. Deep brain stimulation of the nucleus accumbens for the treatment of addiction. Ann N Y Acad Sci. 2013 Apr;1282:119-28. doi: 10.1111/j.1749-6632.2012.06834.x. Epub 2012 Dec 10.

Reference Type RESULT
PMID: 23227826 (View on PubMed)

Denys D, Mantione M, Figee M, van den Munckhof P, Koerselman F, Westenberg H, Bosch A, Schuurman R. Deep brain stimulation of the nucleus accumbens for treatment-refractory obsessive-compulsive disorder. Arch Gen Psychiatry. 2010 Oct;67(10):1061-8. doi: 10.1001/archgenpsychiatry.2010.122.

Reference Type RESULT
PMID: 20921122 (View on PubMed)

Deuschl G, Schade-Brittinger C, Krack P, Volkmann J, Schafer H, Botzel K, Daniels C, Deutschlander A, Dillmann U, Eisner W, Gruber D, Hamel W, Herzog J, Hilker R, Klebe S, Kloss M, Koy J, Krause M, Kupsch A, Lorenz D, Lorenzl S, Mehdorn HM, Moringlane JR, Oertel W, Pinsker MO, Reichmann H, Reuss A, Schneider GH, Schnitzler A, Steude U, Sturm V, Timmermann L, Tronnier V, Trottenberg T, Wojtecki L, Wolf E, Poewe W, Voges J; German Parkinson Study Group, Neurostimulation Section. A randomized trial of deep-brain stimulation for Parkinson's disease. N Engl J Med. 2006 Aug 31;355(9):896-908. doi: 10.1056/NEJMoa060281.

Reference Type RESULT
PMID: 16943402 (View on PubMed)

Voon V, Grodin E, Mandali A, Morris L, Donamayor N, Weidacker K, Kwako L, Goldman D, Koob GF, Momenan R. Addictions NeuroImaging Assessment (ANIA): Towards an integrative framework for alcohol use disorder. Neurosci Biobehav Rev. 2020 Jun;113:492-506. doi: 10.1016/j.neubiorev.2020.04.004. Epub 2020 Apr 13.

Reference Type RESULT
PMID: 32298710 (View on PubMed)

Related Links

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https://brain-pacer.com/

Official study website for the Brain-PACER (Deep Brain Stimulation for Addictions) project, providing information about the trial, research aims, participating sites, and study team.

Other Identifiers

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MR/W020408/1

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

A096527

Identifier Type: -

Identifier Source: org_study_id

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