Alcohol Use DisorderBrain-PACERNCT07341230
Deep Brain Stimulation to Understand and Treat Addiction
A study testing Dual-Target Deep Brain Stimulation, Nucleus Accumbens Deep Brain Stimulation and Ventral Internal Capsule Deep Brain Stimulation in people with Alcohol Use Disorder, run by University of Cambridge at 2 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Alcohol Use Disorder
- What is being tested?
- Dual-Target Deep Brain Stimulation, Nucleus Accumbens Deep Brain Stimulation and Ventral Internal Capsule Deep Brain Stimulation
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 9 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 1 Jul 2025to 31 Oct 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 26Show fewer
- 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
- Inadequate logistical or social support that would impair the safe conduct of deep brain stimulation therapy, including inability to reliably attend scheduled visits, lack of reasonable access to the study site, or inadequate home or caregiver support necessary for postoperative care, device management and follow-up.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom2 sites, 2 recruiting
- Recruiting
Cambridge University Hospitals (Addenbrooke's Hospital)
Cambridge, Cambridgeshire, CB2 0QQ
Samantha N Sallie, PhD, 01223 245151, info@brain-pacer.com
Valerie Voon, MD, PhD
- Recruiting
King's College Hospital
London, Greater London, SE5 9RS
Peter Kosa, MBBS, 02032999000, peter.kosa@nhs.net
David Okai, MD, MRCPsych
About this study
Official title: Deep Brain Stimulation for Disorders of Addiction: Mechanisms and a Pilot Blinded Randomized Cross-over Placebo Controlled Trial
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.
Read the detailed description
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
- Alcohol Use Disorder
- Being tested
- Dual-Target Deep Brain Stimulation, Nucleus Accumbens Deep Brain Stimulation, Ventral Internal Capsule Deep Brain Stimulation, Sham Deep Brain Stimulation
- Keywords
- Alcohol use disorder (AUD), Deep brain stimulation (DBS), Addiction
- Medical subject headings
- Alcoholism, Behavior, Addictive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dual-Target Deep Brain StimulationDevice
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.
Nucleus Accumbens Deep Brain StimulationDevice
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 StimulationDevice
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 StimulationDevice
A surgically implanted deep brain stimulation (DBS) system is present but no therapeutic stimulation is delivered during this condition. All stimulation remains inactive.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Device: Dual-Target Deep Brain Stimulation |
| Single Stimulation - Nucleus Accumbens Only | Active comparator | Participants receive active deep brain stimulation targeting the nucleus accumbens only, with ventral internal capsule stimulation inactive. Receives: Device: Nucleus Accumbens Deep Brain Stimulation |
| 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. Receives: Device: Ventral Internal Capsule Deep Brain Stimulation |
| Sham Stimulation (Inactive) | Sham comparator | Participants receive sham (inactive) deep brain stimulation. The implanted device is turned off; no therapeutic stimulation is provided. Receives: Device: Sham Deep Brain Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Continuously monitored from surgery (Day 1) through the end of Month 10 (study completion)
Secondary outcomes (16)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline (pre-surgery) and monthly during open-label (Months 1-6) and randomized cross-over (Months 6-10) phases.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2026
- Study start1 Jul 2025
- Primary completion31 Oct 2027 (estimated)
- Study completion31 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Alcohol Use DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- This study uses a multiphase design consisting of an initial open-label optimization phase followed by a randomized, double-blind, 4-arm crossover trial.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 9 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Cambridge
- Sponsor type
- University, hospital or other
- Collaborators
- Cambridge University Hospitals NHS Foundation Trust, King's College Hospital NHS Trust
- Responsible party
- Principal investigator, Valerie Voon, University of Cambridge
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07341230
- Sponsor's protocol ID
- A096527
- Other IDs
- MR/W020408/1
- Acronym
- Brain-PACER
- Status last verified
- Mar 2026
- First submitted
- 9 Dec 2025
- Last updated
- 24 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 37329519Davidson 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.
PubMed 35858989Bach 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.
PubMed 36755017Chen 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.
PubMed 30245163Muller 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.
PubMed 23227826Denys 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.
PubMed 20921122Deuschl 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.
PubMed 16943402Voon 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.
PubMed 32298710
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Deep Brain Stimulation for Disorders of Addiction: Mechanisms and a Pilot Blinded Randomized Cross-over Placebo Controlled Trial
- ClinicalTrials.gov ID
- NCT07341230
- Acronym / sponsor ID
- Brain-PACER / A096527
- Conditions
- Alcohol Use Disorder
- Keywords
- Alcohol use disorder (AUD), Deep brain stimulation (DBS), Addiction
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 9 participants (estimated)
- Lead sponsor
- University of CambridgeUniversity, hospital or other
- Collaborators
- Cambridge University Hospitals NHS Foundation Trust, King's College Hospital NHS Trust
- Study start
- 1 Jul 2025 (actual)
- Primary completion
- 31 Oct 2027 (estimated)
- Study completion
- 31 Oct 2027 (estimated)
- First posted
- 14 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 4
- Model description
- This study uses a multiphase design consisting of an initial open-label optimization phase followed by a randomized, double-blind, 4-arm crossover trial.
| Arm | Type | Receives |
|---|---|---|
| Dual Stimulation (Nucleus Accumbens + Ventral Internal Capsule) | Experimental | Device: Dual-Target Deep Brain StimulationParticipants receive active deep brain stimulation simultaneously targeting both the nucleus accumbens and the ventral internal capsule. |
| Single Stimulation - Nucleus Accumbens Only | Active comparator | Device: Nucleus Accumbens Deep Brain StimulationParticipants receive active deep brain stimulation targeting the nucleus accumbens only, with ventral internal capsule stimulation inactive. |
| Single Stimulation - Ventral Internal Capsule Only | Active comparator | Device: Ventral Internal Capsule Deep Brain StimulationParticipants receive active deep brain stimulation targeting the ventral internal capsule only, with nucleus accumbens stimulation inactive. |
| Sham Stimulation (Inactive) | Sham comparator | Device: Sham Deep Brain StimulationParticipants receive sham (inactive) deep brain stimulation. The implanted device is turned off; no therapeutic stimulation is provided. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (26 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dual-Target Deep Brain StimulationA 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. | Device | Dual Stimulation (Nucleus Accumbens + Ventral Internal Capsule) |
| Nucleus Accumbens Deep Brain StimulationA 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. | Device | Single Stimulation - Nucleus Accumbens Only |
| Ventral Internal Capsule Deep Brain StimulationA 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. | Device | Single Stimulation - Ventral Internal Capsule Only |
| Sham Deep Brain StimulationA surgically implanted deep brain stimulation (DBS) system is present but no therapeutic stimulation is delivered during this condition. All stimulation remains inactive. | Device | Sham Stimulation (Inactive) |
Primary outcome
Change in Number of Drinking Days per Week (Timeline Followback)
Time frame: Baseline (6 months pre-surgery), monthly during open-label (Months 1-6) and randomized cross-over (Months 6-10) phases
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.
Change in Number of Alcohol Units Consumed per Week (Timeline Followback)
Time frame: Baseline (6 months pre-surgery), monthly during open-label (Months 1-6) and randomized cross-over (Months 6-10) phases
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.
Adverse Events Related to Surgery or Stimulation
Time frame: Continuously monitored from surgery (Day 1) through the end of Month 10 (study completion)
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.
16 secondary outcomes
Change in Alcohol Craving (Alcohol Urge Questionnaire)
Time frame: 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)
Time frame: Baseline (pre-surgery), monthly during open-label (Months 1-6) and randomized cross-over (Months 6-10) phases
Illness Severity (Clinical Global Impression)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: Continuously monitored from Baseline (pre-surgery) through the end of Month 10 (study completion)
Cognitive Performance (Executive Function, Impulsivity, and Compulsivity Tasks)
Time frame: Baseline (pre-surgery) and monthly during open-label (Months 1-6) and randomized cross-over (Months 6-10) phases.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2026.
- Results publication: PubMed 37329519Rezai 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.
- Results publication: PubMed 35858989Davidson 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.
- Results publication: PubMed 36755017Bach 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.
- Results publication: PubMed 30245163Chen 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.
- Results publication: PubMed 23227826Muller 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.
- Results publication: PubMed 20921122Denys 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.
- Results publication: PubMed 16943402Deuschl 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.
- Results publication: PubMed 32298710Voon 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.
- 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.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Cambridge University Hospitals (Addenbrooke's Hospital)
Cambridge, United Kingdom
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dual-Target Deep Brain Stimulation, Nucleus Accumbens Deep Brain Stimulation and Ventral Internal Capsule Deep Brain Stimulation in people with Alcohol Use Disorder, run by University of Cambridge at 2 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Number of Drinking Days per Week (Timeline Followback) (time frame: Baseline (6 months pre-surgery), monthly during open-label (Months 1-6) and randomized cross-over (Months 6-10) phases). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07341230, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2026.