Health TrialsbyHealthPanel

Deep Brain Stimulation of Treatment-Resistant Bipolar Depression

ConditionBipolar Depression
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age22-64
SponsorWayne Goodman MD

About this trial

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. Medical, psychiatric, and cognitive evaluations. 2. Implantation of a brain stimulation system. 3. Follow up after implantation of device, including programming, recording, and psychiatric testing.

There are risks and benefits to this study which need to be considered when deciding to participate or not. Some of the risks are from surgery, the DBS device and programming, the tests involved, and potential loss of confidentiality, as well as other unknown risks.

Some of the more serious risks involved in this study and the percentage that they occur:

1. Bleeding inside the Brain (1 to 2 percent). 2. Infection from the procedures (3 percent) 3. Seizure caused from the procedures (1.2 percent)

However, the benefit of this study is that it may help relieve or decrease TRBD symptoms. This form of treatment has shown to reduce symptom severity in other cases. This could potentially improve quality of life and activities in daily routines. There is also a potential benefit to society in that the data the investigators will obtain from this study may help increase the understanding of the mechanisms underlying TRBD symptoms, as well as enhanced Deep Brain Stimulation techniques.

Study participation is expected to last 20 months from the time the DBS device is activated and should include approximately 23 visits. These visits also include 8 separate, 24 hour stays at the Menninger NeuroBehvaioral Monitoring Unit (NBU). These 24-hour sessions will occur at multiple points throughout the study (1 week prior to surgery, the week preceding device activation, the week following activation, then after 2 weeks, 4 weeks, 6 months, 9 months, and 12 months). Participants will need to stay locally for the week of the NBU stay (typically Monday through Friday).

Study visits will include clinician administered assessments and questionnaires, subject reported assessments, neuropsychological testing, and mobile behavioral assessments which will occur around 23 visits over the course of 20 months.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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].

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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

  • 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.

Treatment groups

10 Participants
are divided into 2 treatment groups
Group A: Medtronic Percept RC System Implantation for TRBDExperimental treatment 1 intervention
Group B: One Month Blinded Discontinuation PeriodExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

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

Time frame
20 months
2

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

Time frame
20 months
3

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

Time frame
20 months
4

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

Time frame
20 months

Secondary outcomes

1

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

This secondary outcome measure is based on the durability of efficacy by utilizing the MADRS. Durability will be determined by the absence of recurrence of depressive episodes during the subsequent 9 months of observation (3 months stabilization, 6 months follow-up). Recurrence of a depressive episode is defined as a 25% increase of the MADRS over two consecutive monthly visits compared to score at 9 months post-activation = 6 "much worse" or 7 "very much worse" compared to the 9 months post-activation time point. The MADRS is completed by subjects indicating a 0-7. This is a number scale with the higher number being a worse outcome

Time frame
20 months
2

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

Another secondary outcome measure is durability of absence of recurring episodes will be evaluated by the CGI-S. This will be determined by the absence of recurrence of depressive episodes during the subsequent 9 months of observation (3 months stabilization, 6 months follow-up). Recurrence of a depressive episode is defined as a 25% increase of the CGI-S over two consecutive monthly visits compared to score at 9 months post-activation. CGI-S = 6 "much worse" or 7 "very much worse" compared to the 9 months post-activation time point. The CGI-s is completed by subjects indicating a 0-7. This is a number scale with the higher number being a worse outcome

Time frame
20 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Wayne Goodman MD

Lead sponsor

Baylor College of Medicine

Sponsor institution

University of Washington

Collaborator

William Marsh Rice University

Collaborator

Massachusetts General Hospital

Collaborator

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Source ClinicalTrials.gov
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