Deep Brain Stimulation of Treatment-Resistant Bipolar Depression

NCT06599099 | Recruiting DMC FDA Device

• 2 other identifiers: H-537611UH3NS136631
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 4

Brief Summary

This study is only enrolling at Baylor College of Medicine. The other research locations listed serve to support data analysis only. This research study is to investigate the use of technology called Deep Brain Stimulation (DBS) to potentially improve Treatment-Resistant Bipolar Depression (TRBD) symptoms in patients with severe cases. DBS involves the surgical implantation of leads and electrodes into specific areas of the brain, which are thought to influence the disease. A pack implanted in the chest, called the neurotransmitter, keeps the electrical current coursing to the brain through a wire that connects the neurotransmitter and electrodes. It is believed DBS may restore balance to dysfunctional brain circuitry implicated in TRBD. The goal of this study is to enhance current approaches to DBS targeting in the brain and to use a novel approach to find a better and more reliable system for TRBD treatment. Its important for participants to understand that this is an investigational study where there could be a lack of effectiveness in improving TRBD symptoms. There may be no directly benefit from taking part in this study. This study is expected to last 20 months and involves 3 main steps.

1. 1.Medical, psychiatric, and cognitive evaluations.
2. 2.Implantation of a brain stimulation system.
3. 3.Follow up after implantation of device, including programming, recording, and psychiatric testing.
4. 4.Bleeding inside the Brain (1 to 2 percent).
5. 5.Infection from the procedures (3 percent)
6. 6.Seizure caused from the procedures (1.2 percent)

Conditions

Bipolar Depression

Keywords

Treatment Resistant Bipolar Depression

Outcome Measures

Primary Outcomes (4)

• Utilizing the Montgomery-Asberg Depression Ratings Scale (MADRS) as a measurement of Efficacy

  Efficacy: Primary outcome measure is a greater than or equal to 50% reduction on the Montgomery-Asberg Depression Ratings Scale (MADRS) at 9 months post-activation, compared to baseline score, which is obtained about 1 week pre-op. MADRS will evaluate Sadness, tension, Sleep, appetite, Concentration, and thoughts. This is a number scale with the higher number being a worse outcome

  20 months

• Utilizing the Patient-Rated Inventory of Side Effects (PRISE) assessment for adverse events/side effects

  Adverse events will be elicited at each study visit using the PRISE, a standardized self-rating instrument, and confirmed by assessment of the study psychiatrist. Evaluation of manic episodes will be captured by clinical assessment to determine whether patients meet full or partial criteria for hypomanic, manic episodes, or mixed episodes. PRISE will be utilized to review Adverse Event criteria.The PRISE scale includes questions regarding subjects gastrointestinal status, heart status, skin status, nervous system status, eyes/ear status, genital/urinary status, sleep status, sexual functioning status, and "other" status with an area to specify any other concerns. This is a number scale with the higher number being a worse outcome

  20 months

• Evaluation of manic episodes utilizing the Young Mania Rating Scale (YMRS)

  Evaluation of manic episodes will be captured by clinical assessment to determine whether patients meet full or partial criteria for hypomanic, manic episodes, or mixed episodes.This will be based on the Young Mania Rating Scale. This safety measures is administered at: screening, baseline, 1-week post-op, 2 weeks post-op (at activation visit), and then monthly for 20 months. The YMRS rating allows subjects to select from several categories to describe their level of energy. Some items include sleep, energy levels, sex drive, talkativeness, etc. This is a number scale with the higher number being a worse outcome

  20 months

• Evaluation of manic episodes utilizing the Altman Self-Rating Mania Scale (ASRM)

  Evaluation of manic episodes will also be captured based on the self-report on the ASRM rating scale. This safety measures is administered at: screening, baseline, 1-week post-op, 2 weeks post-op (at activation visit), and then monthly for 20 months. The ASRMS rating allows subjects to select from several categories to describe their level of energy. Some items include sleep, energy levels, sex drive, talkativeness, etc. This is a number scale with the higher number being a worse outcome

  20 months

Secondary Outcomes (2)

• Durability of efficacy of the absence of recurring depressive episodes by utilizing the Montgomery-Asberg Depression Ratings Scale (MADRS) .

  20 months

• Durability of efficacy of the absence of recurring depressive episodes by utilizing the Clinical Global Impressions Scale (CGI-S)

  20 months

Study Arms (2)

Medtronic Percept RC System Implantation for TRBD

EXPERIMENTAL

All subjects will receive surgical implantation of Percept RC DBS system

Device: Medtronic Percept RC System

One Month Blinded Discontinuation Period

EXPERIMENTAL

The investigators will use blinded discontinuation at 12 months rather than sham control to establish evidence that response is dependent on ongoing DBS.

Behavioral: One Month Blinded Discontinuation Period

Interventions

Medtronic Percept RC System DEVICE

Medtronic Percept RC System includes: Percept RC neurostimulator SenSight Directional Lead Kit (with and without marker; 33cm and 42cm lengths) SenSight Directional Lead Kit (with and without marker; 33cm and 42cm lengths) SenSight Extension Kit (with and without marker; 40cm, 60cm, and 95cm lengths) Percept DBS Handset and Communicator Kit (patient programmer) SenSight Extension Tunneler Kit SenSight Burr Hole Device Kit Clinician Programmer Application (application runs on Model CT900 Tablet) Percept RC Recharger Kit Recharge Application Software Clinician Communicator/Telemetry Module

Also known as: Deep Brain Stimulation System, DBS

Medtronic Percept RC System Implantation for TRBD

One Month Blinded Discontinuation Period BEHAVIORAL

The investigators will use blinded discontinuation at 12 months rather than sham control to establish evidence that response is dependent on ongoing DBS. The open-label design allows for personalized optimization of programming settings - a strength of this design as related to our study goals. Although one of the goals of this study is to use neural recordings to inform programming, currently, unblinded programming is needed to maximize response and minimize side effects. Adverse events will be elicited at each study visit using a standardized instrument, the Patient-Rated Inventory of Side Effects (PRISE). In addition to monitoring for adverse events related to surgery and stimulation, the investigators will track quality of life (QOLS), global functioning (SDS), and necessary adjustments of medications. The behavioral changes of the subject based on these scales will provide insight to the intervention levels provided from discontinuing the therapy from the device.

One Month Blinded Discontinuation Period

Eligibility Criteria

• Age: 22 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Males and females ages 22-64, inclusive
• Diagnosis: Bipolar I disorder confirmed by SCID-5, currently in a major depressive episode (MDE).
• Symptom Severity: MADRS score of ≥27 at Screening and pre-operative baseline visit. CGI-S \> 4 and YMRS \<12 at these visits.
• Failure to respond or maintain a response to a minimum of four evidence-based interventions for bipolar depression in the patient's lifetime, including at least two FDA-approved medications (olanzapine/fluoxetine, quetiapine, lurasidone, cariprazine, lumateperone), or ECT, administered at adequate doses and duration (adequately defined by the Antidepressant Treatment History Form (ATHF-Short Form). During the current episode, the patient must have failed to respond or maintain a response to a minimum of two FDA-approved interventions for bipolar depression. In addition, the patient is required to be currently taking at least one evidence-based medication for bipolar disorder (e.g., lithium, either alone or in combination with an atypical antipsychotic such as quetiapine), unless no evidence-based medications for bipolar disorder are tolerated.
• Initial mood episode occurred before the age of 40 - to minimize risk of enrolling patients with so atypical onset of initial mania/depression.
• Must be on a stable dose of psychotropic medications for a minimum of four weeks prior to surgery.
• Minimum score on the Montreal Cognitive Assessment (MoCA).
• Able and willing to give informed consent and sign Treatment Contract that includes identification of a reliable informant.

You may not qualify if:

• Lifetime history of a psychotic disorder (e.g., schizophrenia, schizoaffective disorder, and other psychotic disorders), or any history of psychotic symptoms when not in a bipolar mood episode.
• Currently meets criteria for a manic or hypomanic episode or rapid cycling (4 or more mood episodes in the previous 12 months).
• Any psychiatric disorder which is the primary focus of treatment within the past 12 months (with bipolar disorder as the secondary focus of treatment).
• Alcohol/substance use disorder, moderate or severe, within the previous 12 months \[excluding nicotine\].
• Intellectual disability or neurocognitive disorder.
• Current major and/or unstable medical conditions. e.g., liver insufficiency, kidney insufficiency, cardiovascular problems \[unstable arrhythmias, chronic heart failure, myocardial infarction (MI), cardiac pacemaker\], systemic infections, cancer, active upper respiratory infections, endocrinopathies, and any major neurological disorder \[e.g., seizure disorder, stroke, dementia, degenerative neurologic diseases, traumatic brain injury\].
• Any medical contraindication to surgery or condition that makes the patient, in the opinion of the surgeon, a poor candidate.
• Female who is pregnant or breastfeeding or has plans to become pregnant in the next 24 months.
• Any contraindication for MRI.
• Patients with a clinically significant personality disorder, including risk for homicidal or aggressive behavior, which in the opinion of the investigator has a major impact on the patient's current psychiatric status and/or would preclude safe study participation.
• Patients at serious and imminent risk of suicide and not suitable for an outpatient study, in the judgment of the investigators.
• Participation in any investigational clinical trial within the preceding 30 days.
• Current implanted stimulation devices including cardiac pacemakers, defibrillators, and neurostimulators \[including deep brain and spinal cord stimulators\].
• Patients with no regular contact with at least one adult. Patients who are undomiciled are excluded.
• Body mass index (BMI) less than 16 and greater than 40 kg/m2

Sponsors & Collaborators

• Wayne Goodman MD: lead
• University of Washington: collaborator
• Massachusetts General Hospital: collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• William Marsh Rice University: collaborator

Study Sites (4)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

ACTIVE NOT RECRUITING

Baylor College of Medicine

Houston, Texas, 77030, United States

RECRUITING

Rice University

Houston, Texas, 77030, United States

ACTIVE NOT RECRUITING

University of Washington

Seattle, Washington, 98195, United States

ACTIVE NOT RECRUITING

MeSH Terms

Conditions

Bipolar Disorder

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Study Officials

• Wayne Goodman, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michelle Avendano

CONTACT

713-798-4729; mavendan@bcm.edu

Luke Jumper

CONTACT

713-798-4113; jumper@bcm.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Discontinuation: In all cases, the sequence will be as follows in one-week segments: 100% Active (Sham discontinuation), 75% Active, 50% Active, 25% Active, and 0% Active (stim off). They will be told that DBS will be discontinued at some point during the 4 weeks. The programmer will be unblinded and perform "sham" activation. Relapse is defined as a 25% increase of the MADRS over two consecutive visits compared to discontinuation baseline. Escape criteria will include withdrawing consent or significant clinical deterioration warranting unblinding or reinstatement of treatment. Following exit from the discontinuation period, treatment will recommence as clinically indicated including stimulation resumption or continued observation with device off. A stepwise discontinuation over 4 weeks is intended to mitigate rebound effects, striking a balance between scientific need and subject well-being, with escape criteria allowing us to re-initiate therapy if needed for patient safety.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chairman/Professor

Model Details: This model will include 10 subjects between the ages of 22 and 64 with severe, TRBD. These subjects will undergo surgery with DBS leads targeting the ventral capsule/ventral striatum (VC/VS) bilaterally to assess the safety and preliminary efficacy of VC/VS DBS. Subjects will undergo behavioral and clinical testing to provide further insight for alleviating and preventing recurrence of depression and emergence of mania.

Study Record Dates

• First Submitted: August 28, 2024
• First Posted: September 19, 2024
• Study Start: January 1, 2025
• Primary Completion (Estimated): May 30, 2029
• Study Completion (Estimated): May 30, 2030
• Last Updated: January 26, 2026

Record last verified: 2026-01

Locations

US (4)