Deep Brain Stimulation (DBS) for the Treatment of Refractory Alcohol Use Disorder (AUD): Pilot Trial

This is a phase I, non-blinded, non-randomized, pilot trial for safety and efficacy of DBS for AUD. Patients who meet inclusion and exclusion criteria will be identified and recruited from the practices of Sunnybrook psychiatrists. Five (5) to ten (10) subjects will be enrolled and study duration for each patient will be of one (1) year. Our primary objective is to establish the safety of DBS in a patient population with treatment refractory AUD. In addition to demonstrating safety, our second primary objective will be to evaluate if DBS-targeted nucleus accumbens in alcoholism is efficacious in the treatment-refractory patients with AUD. This will be measured by various outcome measures that will include validated scales to assess addiction and craving behaviours.

Study Overview

• Status: Active, not recruiting
• Conditions: Alcohol Use Disorder
• Intervention / Treatment: Device: Deep Brain Stimulation

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria

1. Female or Male patients between age 18-70
2. Diagnosis of alcohol use disorder (AUD) as defined by the Diagnostic and Statistical Manual fifth edition (DSM-5).
3. History of AUD for at least 2 years, with evidence of repeated failure to respond to evidence-based AUD treatments (psychosocial treatments plus pharmacotherapies such as disulfiram, naltrexone and acamprosate).
4. Alcohol Use Disorders Identification Test (AUDIT) Scale Score >8
5. Ability to provide informed consent and comply with all testing, follow-ups and study appointments and protocols

Exclusion criteria

1. Any past or current evidence of psychosis or mania
2. Current suicidal or homicidal ideation
3. Active neurologic disease, such as epilepsy
4. Visible brain damage or atrophy in CT or MRI scan
5. Any contraindication to MRI or positron emission tomography (PET) scanning
6. Likely to relocate or move during the study's one year duration
7. Presence of clinical and/or neurological conditions that may significantly increase the risk of the surgical procedure.
8. Patients with renal dysfunction (GFR<60)
9. Pregnant or lactating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Deep Brain Stimulation Treatment

Device: Deep Brain Stimulation; DBS is a neurosurgical procedure that involves the administration of small amounts of electricity to disrupt abnormal activity of brain structures associated with disease symptoms. It involves inserting thin electrodes into deep brain structures and electrically stimulating them in a controllable and ultimately reversible manner. The electrodes are connected to an internal pulse generator that is implanted in the upper chest region, below the collarbone.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent adverse events (safety and tolerability)	Our primary objective is to establish the safety of deep brain stimulation in a patient population with treatment refractory alcohol use disorder. This is an exploratory pilot study. safety will be reported in the form of adverse event collection, and reported for each patient recruited into the study. Infection, hemorrhage, seizure, sensorymotor disturbance, oculomotor disturbance, or worsening on any adjunctive measure scales used will be reported. These will all be reported on a case-by-case basis, and presented descriptively in the publication. (no specific scale will be used).	6 months
Change in Alcohol consumption measured with the alcohol timeline followback	The amount of alcohol consumption preoperatively will be compared with the amount of alcohol consumption postoperatively using the alcohol timeline followback method at 6 months (compared to the preoperative baseline). This will be administered by a psychometrist, and reported as average number of standard drinks consumed daily and weekly during the 6 month postoperative period. An increase from preoperative values is considered a worse outcome, and a decrease in number is an improvement.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alcohol Dependency Scale	Alcohol Dependency Scale (ADS) will be compared between preoperative baseline and at 6 month follow up.	6 months. This scale is scored out of 47, and will be administered by a psychometrist preoperatively and at 6 months postoperatively. Higher scores are considered worse, so a decrease from baseline is an improvement.
Alcohol Urge Questionnaire (AUQ)	Alcohol Urge Questionnaire (AUQ) will be compared between preoperative baseline and at 6 month follow up. This scale is scored out of 84, and will be administered by a psychometrist preoperatively and at 6 months postoperatively. Higher scores are considered worse, so a decrease from baseline is an improvement.	6 months
Alcohol Use Disorder Identification Test (AUDIT)	Alcohol Use Disorder Identification Test (AUDIT) will be compared between preoperative baseline and at 6 month follow up.	6 months
Hamilton Depression Scale (HAMD)	Hamilton Depression Scale (HAMD) will be compared between preoperative baseline and at 6 month follow up.	6 months
Beck Depression and Anxiety Inventory (BDI and BAI)	Beck Depression and Anxiety Inventory (BDI and BAI) will be compared between preoperative baseline and at 6 month follow up.	6 months. Both the BDI and BAI are scored out of 63, with higher scores indicating a worse outcome. They will be administered by a psychometrist.

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Investigators: Principal Investigator: Nir Lipsman, MD, PhD, Sunnybrook Health Sciences Centre

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2018
• Primary Completion (Estimated): December 25, 2024
• Study Completion (Estimated): December 25, 2024

Study Registration Dates

• First Submitted: August 7, 2018
• First Submitted That Met QC Criteria: September 4, 2018
• First Posted (Actual): September 6, 2018

Study Record Updates

• Last Update Posted (Actual): December 5, 2023
• Last Update Submitted That Met QC Criteria: December 1, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Drinking Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Alcohol Drinking; Alcoholism
• Other Study ID Numbers: 012-2018

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No