Safety and Feasibility of DBS for Bipolar Depression

Official title

Deep Brain Stimulation for Bipolar Depression: Assessing the Safety and Use of Intracranial Neurophenotyping of State Switches

Overview

This study addresses a critical unmet need in the treatment of bipolar disorder by investigating whether Subcallosal Cingulate (SCC) Deep Brain Stimulation (DBS) can safely and effectively treat treatment-resistant bipolar depression without inducing manic switches. The researchers propose to accomplish this by incorporating monitoring of the SCC local field potentials (LFP) for depression tracking and amygdala LFP monitoring for mania prediction while treating Bipolar I patients with SCC DBS Stimulation. This approach could establish a new paradigm for personalized neuromodulation therapy that uses real-time neural monitoring to optimize outcomes while minimizing risks. By incorporating bilateral, dual-site LFP monitoring from both the SCC and amygdala, this research will allow the researchers to assess the therapeutic efficacy of continuous SCC-DBS and develop novel safety biomarkers that could transform the clinical management of DBS therapy in psychiatry. The findings will have immediate implications for clinical practice and will advance the study team's fundamental understanding of the neural circuits underlying mood regulation and dysregulation in bipolar disorder.

Interventions

• Device Medtronic Percept PC DBS system
  Open label active Deep Brain Stimulation (DBS) with continuous monitoring of local field potentials (LFP) from the SCC and amygdala.

Primary outcome measures

• Hamilton Depression Rating Scale (HDRS) [Time frame: Baseline and weekly up to 1 year]

Secondary outcome measures (1)

• Young Mania Rating Scale (YMRS) [Time frame: Baseline and weekly up to 1 year]

Eligibility criteria

Inclusion criteria

• Age 22-70 years
• Ability to provide written informed consent
• Primary diagnosis of Bipolar I Disorder confirmed by SCID-5
• Current major depressive episode (MDE) of at least 12 months duration
• Stable control of mania for a minimum of 1 year
• Agreement to remain on current anti-mania medication regimen
• Hamilton Depression Rating Scale-17 (HDRS-17) score ≥20 at screening and baseline
• Young Mania Rating Scale (YMRS) score <12 at screening and baseline
• Treatment-resistant depression: failure to respond to at least 4 adequate trials of antidepressant treatment in the current episode. Antidepressant treatments include: Medications (Must include 2 antidepressant medications from different pharmacological classes), Psychotherapy, ECT, repetitive transcranial magnetic stimulation (rTMS), IV ketamine or intra-nasal esketamine.
• All patients must be receiving at least one mood stabilizing medication at entry into the trial. Medication regimen must be stable for a minimum of 4 weeks before the baseline visit.
• Able to provide informed consent
• English-speaking
• Deemed suitable surgical candidate by neurosurgical evaluation
• Under care of treating psychiatrist willing to collaborate with study team
• Able to reside in New York Metropolitan area during first 6 months or willing/able to travel monthly to study site
• Provision of at least two emergency contacts age ≥22 residing within reasonable proximity

Exclusion criteria

• Current manic or hypomanic episode (YMRS ≥12)
• Rapid cycling pattern (≥4 mood episodes in the past 12 months)
• Active suicidal ideation with intent or plan
• Suicide attempt within six months prior to baseline
• Current psychotic symptoms
• Primary diagnosis of schizophrenia, schizoaffective disorder, or other psychotic disorder
• History (current and/or lifetime) of one or more schizophrenia-spectrum or other psychotic disorders including: schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, and major depressive disorder with psychosis (unipolar or bipolar), and/or psychotic depression (unipolar or bipolar) (does not include psychosis occurring in the context of a manic episode of a subject with bipolar disorder)
• Substance use disorder (moderate or severe) within 6 months
• Presence of any type of dementia / Major Neurocognitive Disorder / significant cognitive impairment interfering with study participation
• Subject has had a prior VNS Therapy or deep brain stimulation (DBS) implant
• Subject has a diagnosis of Substance Use Disorder as defined by the DSM-V without sustained remission (12 months or longer)
• History of borderline or severe personality disorder, as determined by clinical judgment, which would significantly interfere with a subject's participation in the study
• Active primary diagnosis of one or more of the following disorders: obsessive-compulsive disorder, eating disorder, or post-traumatic stress disorder
• Cognitive or psychiatric deficit (e.g., amnesia, delirium) that in the investigator's judgment would interfere with the subject's ability to accurately complete study assessments
• Current or lifetime history of psychotic features in any major depressive episode (MDE)
• Treatment with another investigational device or investigational drugs
• Contraindications to MRI (metallic implants, claustrophobia unmanageable with anxiolytics)
• Contraindications to general anesthesia or neurosurgery
• Significant structural brain abnormalities precluding safe electrode placement
• Active infection or immunocompromised state
• Active unstable medial condition (diabetes, heart disease, hypertension, cancer, endocrine)
• BMI >35; and/or CRP >3
• Coagulopathy or anticoagulation that cannot be safely interrupted
• Pregnancy or planning pregnancy during study period
• Women of childbearing potential unwilling to use effective contraception
• Prisoners or institutionalized individuals
• Decisionally impaired individuals (unless previously consented when capacitated)
• Special status patients (employees, VIPs, celebrities, public figures) unless consented before special status known

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

United States · 1 center

• Center for Advanced Circuit Therapeutics, Clinical Neurosciences Center, Mount Sinai West — New York

Identifiers

NCT: NCT07745374 · STUDY-26-00089 · DG251219

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗