Deep Brain Stimulation for Disorders of Addiction: Mechanisms and a Pilot Blinded Randomized Cross-over Placebo Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 9
- 试验地点
- 2
- 主要终点
- Change in Number of Drinking Days per Week (Timeline Followback)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •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.
结局指标
主要结局
Change in Number of Drinking Days per Week (Timeline Followback)
时间窗: 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)
时间窗: 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
时间窗: 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.
次要结局
- Illness Severity (Clinical Global Impression)(Baseline (pre-surgery), monthly 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)
- 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)
- 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)
- Daily Ecological Momentary Assessment of Depressive Symptoms (PHQ-9 Items)(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)(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)(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)(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)(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)(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(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(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(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)(Continuously monitored from Baseline (pre-surgery) through the end of Month 10 (study completion))
- Cognitive Performance (Executive Function, Impulsivity, and Compulsivity Tasks)(Baseline (pre-surgery) and monthly during open-label (Months 1-6) and randomized cross-over (Months 6-10) phases.)
研究者
Valerie Voon
Professor Valerie Voon, Professor of Neuropsychiatry and Neuromodulation, Department of Psychiatry, University of Cambridge
University of Cambridge