Deep Brain Stimulation to Understand and Treat Addiction (Brain-PACER)

University of Cambridge

Status: Enrolling

Conditions: Alcohol Use Disorder

Treatments: Device: Dual-Target Deep Brain Stimulation; Device: Ventral Internal Capsule Deep Brain Stimulation; Device: Nucleus Accumbens Deep Brain Stimulation; Device: Sham Deep Brain Stimulation

Study type: Interventional

Funder types: Other

Identifiers

NCT07341230

MR/W020408/1 (Other Grant/Funding Number)

A096527

Details and patient eligibility

About

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.

Full 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.

Enrollment: 9 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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9 participants in 4 patient groups

Dual Stimulation (Nucleus Accumbens + Ventral Internal Capsule)

Experimental group

Description:

Participants receive active deep brain stimulation simultaneously targeting both the nucleus accumbens and the ventral internal capsule.

Treatment:

Device: Dual-Target Deep Brain Stimulation

Single Stimulation - Nucleus Accumbens Only

Active Comparator group

Description:

Participants receive active deep brain stimulation targeting the nucleus accumbens only, with ventral internal capsule stimulation inactive.

Treatment:

Device: Nucleus Accumbens Deep Brain Stimulation

Single Stimulation - Ventral Internal Capsule Only

Active Comparator group

Description:

Participants receive active deep brain stimulation targeting the ventral internal capsule only, with nucleus accumbens stimulation inactive.

Treatment:

Device: Ventral Internal Capsule Deep Brain Stimulation

Sham Stimulation (Inactive)

Sham Comparator group

Description:

Participants receive sham (inactive) deep brain stimulation. The implanted device is turned off; no therapeutic stimulation is provided.

Treatment:

Device: Sham Deep Brain Stimulation