Deep Brain Stimulation to Understand and Treat Addiction

University of Cambridge9 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Alcohol Use Disorder

Interventions

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 Stimulation

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 Years

Medical Language ↔ Plain English

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

Locations (2)

Cambridge University Hospitals (Addenbrooke's Hospital)

Cambridge, Cambridgeshire, United Kingdom

RECRUITING

King's College Hospital

London, Greater London, United Kingdom

RECRUITING

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: Continuously monitored from surgery (Day 1) through the end of Month 10 (study completion)

Secondary Outcomes

Change in Alcohol Craving (Alcohol Urge Questionnaire)

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

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.

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.

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)

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.

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)

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.

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)

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.

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)

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.

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)

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.