Deep Brain Stimulation to Understand and Treat Addiction
Brain-PACER
Deep Brain Stimulation for Disorders of Addiction: Mechanisms and a Pilot Blinded Randomized Cross-over Placebo Controlled Trial
2 other identifiers
interventional
9
1 country
2
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for not_applicable
Started Jul 2025
Typical duration for not_applicable
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 1, 2025
CompletedFirst Submitted
Initial submission to the registry
December 9, 2025
CompletedFirst Posted
Study publicly available on registry
January 14, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 31, 2027
March 24, 2026
March 1, 2026
2.3 years
December 9, 2025
March 22, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Change in Number of Drinking Days per Week (Timeline Followback)
Alcohol use will be assessed using the Timeline Followback (TLFB), a validated self-report measure of daily alcohol consumption. Participants will report the number of days per week on which alcohol was consumed. TLFB data are collected for a 6-month pre-surgical baseline, monthly during the 6-month open-label optimization phase, and monthly during the 4-month randomized cross-over phase. Changes in drinking frequency across phases and stimulation conditions will be compared to evaluate the effect of deep brain stimulation on alcohol use.
Baseline (6 months pre-surgery), monthly during open-label (Months 1-6) and randomized cross-over (Months 6-10) phases
Change in Number of Alcohol Units Consumed per Week (Timeline Followback)
Weekly alcohol intake will be quantified using the Timeline Followback (TLFB). The total number of standard UK alcohol units consumed per week will be calculated from participant self-report. TLFB data are collected for a 6-month pre-surgical baseline, monthly during the 6-month open-label optimization phase, and monthly during the 4-month randomized cross-over phase. Changes in total weekly consumption across phases and stimulation conditions will be compared to determine the effect of deep brain stimulation on overall drinking volume.
Baseline (6 months pre-surgery), monthly during open-label (Months 1-6) and randomized cross-over (Months 6-10) phases
Adverse Events Related to Surgery or Stimulation
All adverse events related to DBS surgery, the implanted device, or stimulation are recorded and reviewed by the clinical and research teams. Events are categorized by severity (mild, moderate, severe) and relatedness (unrelated, possibly related, related). Higher severity classifications indicate more serious adverse outcomes.
Continuously monitored from surgery (Day 1) through the end of Month 10 (study completion)
Secondary Outcomes (16)
Change in Alcohol Craving (Alcohol Urge Questionnaire)
Baseline (pre-surgery), daily during open-label (Months 1-6) and randomized cross-over (Months 6-10) phases
Quality of Life (Short Form Health Survey)
Baseline (pre-surgery), monthly during open-label (Months 1-6) and randomized cross-over (Months 6-10) phases
Illness Severity (Clinical Global Impression)
Baseline (pre-surgery), monthly during open-label (Months 1-6) and randomized cross-over (Months 6-10) phases
Momentary Mood, Craving, Anxiety (0-100 VAS via WebApp)
Up to five times daily from Baseline (pre-surgery), during open-label (Months 1-6) and randomized cross-over (Months 6-10) phases
Cue-Induced Alcohol Craving (0-100 VAS Following Presentation of Personalized Alcohol Cues)
During perioperative laboratory testing (Days 1-7) and monthly laboratory sessions during open-label (Months 1-6) and RCT (Months 6-10) phases
- +11 more secondary outcomes
Study Arms (4)
Dual Stimulation (Nucleus Accumbens + Ventral Internal Capsule)
EXPERIMENTALParticipants receive active deep brain stimulation simultaneously targeting both the nucleus accumbens and the ventral internal capsule.
Single Stimulation - Nucleus Accumbens Only
ACTIVE COMPARATORParticipants receive active deep brain stimulation targeting the nucleus accumbens only, with ventral internal capsule stimulation inactive.
Single Stimulation - Ventral Internal Capsule Only
ACTIVE COMPARATORParticipants receive active deep brain stimulation targeting the ventral internal capsule only, with nucleus accumbens stimulation inactive.
Sham Stimulation (Inactive)
SHAM COMPARATORParticipants receive sham (inactive) deep brain stimulation. The implanted device is turned off; no therapeutic stimulation is provided.
Interventions
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.
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.
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.
A surgically implanted deep brain stimulation (DBS) system is present but no therapeutic stimulation is delivered during this condition. All stimulation remains inactive.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
- +11 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Cambridgelead
- Cambridge University Hospitals NHS Foundation Trustcollaborator
- King's College Hospital NHS Trustcollaborator
Study Sites (2)
Cambridge University Hospitals (Addenbrooke's Hospital)
Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom
King's College Hospital
London, Greater London, SE5 9RS, United Kingdom
Related Publications (8)
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.
PMID: 37329519RESULTDavidson 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.
PMID: 35858989RESULTBach 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.
PMID: 36755017RESULTChen 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.
PMID: 30245163RESULTMuller 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.
PMID: 23227826RESULTDenys 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.
PMID: 20921122RESULTDeuschl 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.
PMID: 16943402RESULTVoon 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.
PMID: 32298710RESULT
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor Valerie Voon, Professor of Neuropsychiatry and Neuromodulation, Department of Psychiatry, University of Cambridge
Study Record Dates
First Submitted
December 9, 2025
First Posted
January 14, 2026
Study Start
July 1, 2025
Primary Completion (Estimated)
October 31, 2027
Study Completion (Estimated)
October 31, 2027
Last Updated
March 24, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
- Time Frame
- Beginning 12 months after publication of primary results and for up to 5 years thereafter.
- Access Criteria
- Requests should be directed to the Chief Investigator (Professor Valerie Voon) via the University of Cambridge and will require a data-sharing agreement approved by the Sponsor.
De-identified individual participant data (IPD) that underlie published results may be shared with researchers upon reasonable request, following approval by the study investigators and institutional ethics committees. Data will be shared in accordance with relevant data protection regulations and participant consent. No personally identifiable information will be released.