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| ID | Type | Description | Link |
|---|---|---|---|
| MR/W020408/1 | Other Grant/Funding Number | Medical Research Council |
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| Name | Class |
|---|---|
| Cambridge University Hospitals NHS Foundation Trust | OTHER |
| King's College Hospital NHS Trust | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dual Stimulation (Nucleus Accumbens + Ventral Internal Capsule) | Experimental | Participants receive active deep brain stimulation simultaneously targeting both the nucleus accumbens and the ventral internal capsule. |
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| Single Stimulation - Nucleus Accumbens Only | Active Comparator | Participants receive active deep brain stimulation targeting the nucleus accumbens only, with ventral internal capsule stimulation inactive. |
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| Single Stimulation - Ventral Internal Capsule Only | Active Comparator | Participants receive active deep brain stimulation targeting the ventral internal capsule only, with nucleus accumbens stimulation inactive. |
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| Sham Stimulation (Inactive) | Sham Comparator | Participants receive sham (inactive) deep brain stimulation. The implanted device is turned off; no therapeutic stimulation is provided. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dual-Target Deep Brain Stimulation | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Alcohol Craving (Alcohol Urge Questionnaire) | Alcohol craving will be assessed using the Alcohol Urge Questionnaire (AUQ), a validated self-report measure of desire to drink, anticipated effects, and perceived control over drinking. Scores range from 8 to 56, with higher scores indicating stronger craving. Participants complete the AUQ daily during the open-label and randomized phases and monthly during laboratory sessions. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cambridge University Hospitals (Addenbrooke's Hospital) | Recruiting | Cambridge | Cambridgeshire | CB2 0QQ | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37329519 | Result | 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. | |
| 35858989 |
| Label | URL |
|---|---|
| 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. | View source |
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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.
Beginning 12 months after publication of primary results and for up to 5 years thereafter.
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.
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| ID | Term |
|---|---|
| D000437 | Alcoholism |
| D016739 | Behavior, Addictive |
| ID | Term |
|---|---|
| D019973 | Alcohol-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D046690 | Deep Brain Stimulation |
| ID | Term |
|---|---|
| D004599 | Electric Stimulation Therapy |
| D013812 | Therapeutics |
| D013514 | Surgical Procedures, Operative |
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This study uses a multiphase design consisting of an initial open-label optimization phase followed by a randomized, double-blind, 4-arm crossover trial.
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| Nucleus Accumbens Deep Brain Stimulation | 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. |
|
| Ventral Internal Capsule Deep Brain Stimulation | 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 Deep Brain Stimulation | Device | A surgically implanted deep brain stimulation (DBS) system is present but no therapeutic stimulation is delivered during this condition. All stimulation remains inactive. |
|
| 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) | Health-related quality of life will be assessed with the Short Form Health Survey (SF-36), a 36-item self-report measure comprising eight domains of physical and mental health. Domain scores are transformed to a 0-100 scale, with higher scores indicating better health status. Physical and Mental Component Summary scores may also be calculated, with higher scores reflecting better quality of life. | Baseline (pre-surgery), monthly during open-label (Months 1-6) and randomized cross-over (Months 6-10) phases |
| Illness Severity (Clinical Global Impression) | Illness severity and clinical change over time will be assessed with The Clinical Global Impression (CGI) scale. The CGI-Severity (CGI-S) is a clinician-rated measure of current illness severity ranked on a 7-point scale, whereby the CGI-Improvement (CGI-I) rates change from baseline on a 7-point scale. Lower scores indicate lower severity and greater improvement. | 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) | Participants complete high-frequency ecological momentary assessments (EMAs) via a smartphone-based web application up to five times per day. Each EMA consists of composite of single-item visual analogue scale (VAS) questions assessing current depression, anxiety, and craving (e.g., "What is your craving right now?"). Responses are recorded on a continuous scale from 0 to 100, where 0 indicates none/not at all and 100 indicates the most extreme level. Higher scores indicate greater levels of the assessed state. | 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) | Cue-induced craving is assessed using a 0-100 visual analogue scale immediately after viewing personalized alcohol-related cues in laboratory sessions. Participants rate their urge to drink after each cue, with 0 representing "no urge" and 100 representing the "strongest imaginable urge." Higher scores indicate stronger cue-induced craving. | During perioperative laboratory testing (Days 1-7) and monthly laboratory sessions during open-label (Months 1-6) and RCT (Months 6-10) phases |
| Daily Ecological Momentary Assessment of Depressive Symptoms (PHQ-9 Items) | Depressive symptoms are assessed once daily using a battery comprising the nine items of the Patient Health Questionnaire-9 (PHQ-9), adapted for daily assessment. Items are administered via a smartphone-accessible Qualtrics survey and assess current depressive symptom severity. Each item is rated using a continuous visual analogue scale (VAS) ranging from 0 (not at all) to 100 (most extreme). Higher scores indicate greater depressive symptom severity. | Once daily from Baseline (pre-surgery), during the 6-month open-label optimization (Months 1-6) and 4-month RCT (Months 6-10) phases |
| Daily Ecological Momentary Assessment of Anxiety Symptoms (GAD-7 Items) | Anxiety symptoms are assessed once daily using a battery comprising the seven items of the Generalized Anxiety Disorder-7 (GAD-7), adapted for daily assessment. Items are administered via a smartphone-accessible Qualtrics survey and assess current anxiety symptom severity. Each item is rated using a continuous visual analogue scale (VAS) ranging from 0 (not at all) to 100 (most extreme). Items are not rated using Likert-type response options. Higher scores indicate greater anxiety symptom severity. | Once daily from Baseline (pre-surgery), during the 6-month open-label optimization (Months 1-6) and 4-month RCT (Months 6-10) phases |
| Daily Ecological Momentary Assessment of Alcohol Urge (AUQ Items) | Alcohol urge is assessed once daily using an ecological momentary assessment (EMA) battery comprising the eight items of the Alcohol Urge Questionnaire (AUQ), adapted for daily assessment. Items are administered via a smartphone-accessible survey and assess current alcohol urge. Each item is rated using a continuous visual analogue scale (VAS) ranging from 0 (no urge) to 100 (strongest urge). Items are not rated using Likert-type response options. Higher scores indicate greater alcohol urge. | Once daily from Baseline (pre-surgery), during the 6-month open-label optimization (Months 1-6) and 4-month RCT (Months 6-10) phases |
| Daily Assessment of Delay Discounting (Monetary Choice Questionnaire) | Delay discounting is assessed once daily using the Monetary Choice Questionnaire (MCQ), administered via a smartphone-accessible Qualtrics survey. The MCQ comprises a series of 27 choice items in which participants select between a smaller, sooner monetary reward and a larger, later monetary reward. Each item requires a forced choice between the shorter-delay and longer-delay option. Responses are used to characterize individual differences in delay discounting, with a stronger preference for sooner rewards reflecting steeper discounting. | Once daily from Baseline (pre-surgery), during the 6-month open-label optimization (Months 1-6) and 4-month RCT (Months 6-10) phases |
| Daily Assessment of Risk-Taking Behavior (Mixed Gamble Task) | Risk-taking behavior is assessed once daily using a mixed gamble decision-making task administered via an online application. On each of the 80 total trials, participants are presented with gambles offering a 50% probability of monetary gain and a 50% probability of monetary loss, with the magnitudes of potential gains and losses varying across trials. Participants indicate whether they would accept or reject each gamble. Patterns of acceptance and rejection across varying gain-loss combinations are used to characterize individual differences in risk-taking behavior, with greater acceptance of gambles indicating increased risk-taking. | Once daily from Baseline (pre-surgery), during the 6-month open-label optimization (Months 1-6) and 4-month RCT (Months 6-10) phases |
| Compulsive Alcohol-Related Thoughts and Behaviours (Obsessive-Compulsive Drinking Scale) | Compulsive alcohol-related thoughts and behaviors are assessed using the Obsessive-Compulsive Drinking Scale (OCDUS). Scores range from 0 to 56, with higher scores indicating more severe obsessive thoughts, urges, and loss of control related to drinking. Participants complete the OCDUS monthly to evaluate changes across study phases. | Baseline (pre-surgery) and monthly during open-label (Months 1-6) and randomized cross-over (Months 6-10) phases |
| Local Field Potential (LFP) Activity During Rest and Task Performance | Local field potentials (LFPs) are recorded from implanted deep brain stimulation electrodes during resting-state periods and during computerized behavioral tasks. LFP recordings are used to characterize neural activity associated with behavioral state and task performance. | During perioperative phase (Days 1-7), and monthly during open-label (Months 1-6) and RCT (Months 6-10) phases |
| Scalp Electroencephalography (EEG) Activity During Rest and Task Performance | Scalp electroencephalography (EEG) is recorded during resting-state periods and during computerized behavioral tasks. EEG recordings are used to characterize cortical neural activity associated with behavioral state and task performance. | During perioperative phase (Days 1-7), and monthly during open-label (Months 1-6) and RCT (Months 6-10) phases |
| Peripheral Physiological Activity During Laboratory Task Performance | Peripheral physiological signals are recorded during laboratory sessions while participants complete resting-state assessments and computerized behavioral tasks. Measures include heart rate, heart rate variability, and galvanized skin response, and are used to characterize autonomic and physiological responses associated with task performance. | During perioperative phase (Days 1-7), and monthly during open-label (Months 1-6) and RCT (Months 6-10) phases |
| Continuous Peripheral Physiological Activity During Daily Life (Wearable Monitoring) | Peripheral physiological signals are continuously recorded during daily life using a wearable device. Measures include heart rate, heart rate variability, and galvanized skin response, and are used to characterize autonomic and physiological activity over time outside the laboratory setting. | Continuously monitored from Baseline (pre-surgery) through the end of Month 10 (study completion) |
| Cognitive Performance (Executive Function, Impulsivity, and Compulsivity Tasks) | Cognitive domains including executive function, impulsivity, and compulsivity are assessed during laboratory sessions using a battery of validated computerized behavioral tasks. Tasks are designed to probe components of cognitive control, decision-making, and behavioral flexibility. Performance measures derived from these tasks are used to characterize individual differences in these cognitive domains. | Baseline (pre-surgery) and monthly during open-label (Months 1-6) and randomized cross-over (Months 6-10) phases. |
| King's College Hospital | Recruiting | London | Greater London | SE5 9RS | United Kingdom |
|
| Result |
| 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. |
| 36755017 | Result | 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. |
| 30245163 | Result | 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. |
| 23227826 | Result | 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. |
| 20921122 | Result | 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. |
| 16943402 | Result | 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. |
| 32298710 | Result | 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. |
| D003192 | Compulsive Behavior |
| D007175 | Impulsive Behavior |
| D001519 | Behavior |