HABITS Study (Helping Addiction by Individualized Therapeutic Stimulation): Pilot Trial of Deep Brain Stimulation Guided By Stereoelectroencephalography for Treatment-Refractory Substance Use Disorders

Overview

Substance use disorder (SUD) or addiction to drugs/alcohol is a devastating disease. Over 40,000 overdose deaths have happened in Canada since 2016, 1 in 5 Canadians will have a SUD, and 70% of those with SUD continue to relapse, showing that we urgently need new treatments. The Helping Addiction by Individualized Therapeutic Stimulation (HABITS) Study is exploring deep brain stimulation (DBS) for people who have failed to quit harmful substances. Over 250,000 people have received DBS, which is well-established for Parkinson's disease and has evidence of success in major depression and obsessive-compulsive disorder. DBS uses electricity to directly stimulate areas of the brain. However, for DBS to work effectively, it needs to be personalized to each individual, which will be pursued through stereoelectroencephalography (SEEG). DBS and SEEG are minimally invasive and reversible, with a low risk of side effects. SEEG started over 70 years ago to find seizure location in the brain of children and adults with epilepsy. It now has been used for major depression and chronic pain to guide DBS. It involves inserting electrodes temporarily across critical brain areas and monitoring patients for several days. SEEG can provide an understanding of where addiction and craving are in the brain to guide the placement of DBS electrodes and device settings that are optimal for a person. In the HABITS Study, 10 participants will receive DBS guided by SEEG and undergo 11 study visits. Individuals will first undergo detoxification with CAMH. Then, they will receive DBS and SEEG at Toronto Western Hospital, where they will stay for 1 to 2 weeks. Finally, they will be followed for a year, where they will receive standard psychiatric care. SUD causes heavy burdens on individuals, families, healthcare systems, and society. The HABITS Study promises to personalize DBS to treat those who are struggling with severe addiction.

Detailed description

Deep brain stimulation (DBS) is a promising treatment for substance use disorder (SUD) as it can precisely target and modulate aberrant disease-implicated neural networks. It has the unique ability to directly stimulate deep brain structures and deliver long-term electrical stimulation. DBS is minimally invasive, reversible, and non-ablative, with a minor risk of serious adverse events. DBS is well-established for movement disorders, with over 250,000 procedures performed, and has FDA breakthrough device status for major depression and OCD. A 2023 review of DBS for SUD demonstrated its tremendous promise, with an average clinical improvement of 60%. But with only approximately 50 patients with SUD receiving DBS worldwide, more studies are urgently required.

Although one of the strengths of DBS is its ability to be individualized to patients, doing so is difficult. Two critical barriers of DBS are 1) identifying optimal DBS electrode targets as many brain areas are implicated in addiction and 2) selecting the correct stimulation settings as many are possible and detecting immediate effects of settings is difficult (in contrast to movement disorders, such as immediate tremor cessation).

In the HABITS Study, we aim to address these shortcomings by using stereoelectroencephalography (SEEG), a comprehensive drug craving provocation paradigm, and a newly developed AI driven analysis pipeline. SEEG has been in use since the 1960s and is the gold standard for medication-resistant epilepsy, which involves the implantation of intracranial electrodes across the brain, providing continuous electrophysiological recordings for multiple days to identify seizure location. SEEG has been recently used to guide DBS for major depression and chronic pain.

By leveraging SEEG to elucidate an objective, predictive biomarker of addiction (e.g., craving), this can be used to better guide DBS target selection and stimulation setting to improve the effectiveness of DBS for patients with SUD.

Interventions

• Device deep brain stimulation and stereoelectroencephalography
  Deep brain stimulation guided by stereoelectroencephalography

Primary outcome measures

• Number of Participants with Treatment-Related Adverse Events [Time frame: From enrolment to study conclusion at 12 months.]
• Feasibility Assessed by Recruitment Rates and Protocol Adherence [Time frame: Across 3 years of the anticipated study length.]

Secondary outcome measures (6)

• Proportion of Negative Urine Toxicology for Primary Substance (%) Assed by Urinalysis [Time frame: From enrolment to study conclusion at 12 months.]
• Change From Baseline in Days of Primary Substance Use Assessed by Timeline Follow-Back Self-Report [Time frame: From enrolment to study conclusion at 12 months.]
• Self-Reported Substance Craving Assessed Using a 0-10 Visual Analog Scale [Time frame: From enrolment to study conclusion at 12 months.]
• Depressive Symptom Severity Assessed by Patient Health Questionnaire (PHQ-9) [Time frame: From enrolment to study conclusion at 12 months.]
• Anxiety Symptom Severity Asssed by General Anxiety Disorder (GAD-7) [Time frame: From enrolment to study conclusion at 12 months.]
• Electrophysiology Activity Correlating with Craving Assed by Brain Recordings Using Deep Brain Stimulation Electrodes and Stereoelectroencephalography [Time frame: From enrolment to 12 months.]

Eligibility criteria

Inclusion criteria

• Adult, Age 25-65
• Severe DSM-5 substance use disorder (SUD) as assessed by Structured Clinical Interview for DSM-5 (SCID-5)
• Treatment refractory as evidenced by non-response to an adequate trial of ≥2 evidence-based treatment modalities for their substance use disorder in the most recent 3 years of illness, as determined by the study clinical team
• Able to comply with study visit schedule and timeline
• Stable housing and reliable transportation
• Treatment-seeking (>7 on a 0-10 readiness ruler and open to the end-of-treatment outcome of abstinence)
• Capable of understanding and providing informed consent

Exclusion criteria

• Contraindications to neurosurgical interventions such as major medical co-morbidities, including uncontrolled hypertension, coagulopathy, severe diabetes, major organ system failure, active infection or history of implant-related infections, immunocompromised state, or malignancy with <5 years life expectancy
• Contraindications for MRI, including implanted metallic devices (e.g., non-MRI-safe cardiac pacemaker or neurostimulator; some artificial joints metal pins; surgical clips; or other implanted metal parts), or claustrophobia or discomfort in confined spaces
• Cardiac pacemaker/defibrillator, or other implanted stimulator
• Presence of epilepsy, stroke, or degenerative disorder of the nervous system
• Serious problems with literacy, vision, or hearing

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Canada · 1 center

• Centre for Addiction and Mental Health / Toronto Western Hospital — Toronto

Identifiers

NCT: NCT06973512 · CTO Project ID: 4520

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗