Major Depressive DisorderNCT02046330
Deep Brain Stimulation (DBS) Therapy for Treatment Resistant Depression
A study testing Deep Brain Stimulation Model 3387 Model 3389 in people with Major Depressive Disorder and Treatment Resistant Depression, run by The University of Texas Health Science Center, Houston at 1 site in United States.
Trial summary
We propose a clinical study of medial forebrain bundle DBS as a treatment in 20 patients with treatment refractory depression (TRD). Data from the University of Bonn indicates that surgical lesions of the medical forebrain bundle can produce therapeutic benefits in patients with depressive disorders, and suggest that… Read more about this study
- Who is it for?
- Ages 22 to 70 years
- Conditions the study is for
- Major Depressive Disorder, Treatment Resistant Depression
- What is being tested?
- Deep Brain Stimulation Model 3387 Model 3389
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Dec 2013to 1 Apr 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 22 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Major Depression Disorder (MDD) diagnosed by Structured Clinical Interview for DSM-IV (SCID I/DSM-IV), judged to be of disabling severity.
- Age 22 - 70 years.
- 24-item Hamilton Depression Rating Scale (HDRS) score of at least 21 on the first 17 items
- Global Assessment of Function (GAF) score of 45 or less.
- A recurrent (equal or >4 episodes) or chronic (episode duration equal or higher >2 years) course AND a minimum of 5 years since the onset of the first depressive episode. Major impairment in functioning or potentially severe medical outcomes (repeated hospitalizations, serious suicidal or other self-injurious behavior).
- Failure to respond to: 6.1. Adequate trials (equal or >6 weeks at the maximum recommended or tolerated dose) of primary antidepressants from at least 3 different classes AND; 6.2. adequate trials ( equal>4 weeks at the usually recommended or maximum tolerated dose) of augmentation/combination of a primary antidepressant using at least 2 different augmenting/combination agents (lithium, T3, stimulants, neuroleptics, anticonvulsants, buspirone, or a second primary antidepressant) AND; 6.3 An adequate trial of ECT (>6 bilateral treatments), or inability to tolerate an adequate ECT trial, AND; 6.4 An adequate trial of individual psychotherapy (>20 sessions with an experienced psychotherapist).
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- Able to comply with the operational and administrative requirements of participation in the study.
- Able to give written informed consent
- On a stable drug regimen of psychotropic medication for at least 6 weeks at the time of entry into the study.
- Good general health. No changes in medication treatment during participation in study.
Who cannot join
- Current or past non-affective psychotic disorder, Bipolar Disorder, Schizophrenia, or Schizoaffective disorder. Patients who suffer from generalized anxiety disorder will be permitted to participate as long as MDD is the primary clinical diagnosis.
- Any current clinically significant neurological disorder, including dementia or medical illness affecting brain function.
- Any clinically significant abnormality on preoperative magnetic resonance imaging (MRI).
- Any previous surgery to destroy the region of the brain that will be the target of treatment.
- Any surgical contraindications to undergoing DBS, including labeled contraindications for DBS and/or inability to undergo presurgical MRI (cardiac pacemaker, implantable defibrillator or other implantable stimulator, pregnancy, metal in body, severe claustrophobia), infection, coagulopathy, inability to undergo an awake operation, significant cardiac or other medical risk factors for surgery.
- Refusal of an adequate trial of ECT.
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- History of stimulation intolerance in any area of the body.
- Current or unstably remitted substance abuse or dependence. No alcohol and/or substance abuse or dependence in the past 6 months.
- Pregnancy and women of childbearing age not using effective contraception. Double-barrier method is required.
- History of severe personality disorder, where, based on the judgment of the investigators, the personality disorder will interfere with the patient's ability to complete the follow-up protocol, e.g. borderline personality disorder.
- Imminent risk of suicide
- Participation in another drug, device, or biologics trial within the preceding 30 days
- Presence of a condition requiring routine MRIs.
- Presence of a condition requiring diathermy.
- Subject is on anticoagulant medication.
- Not able to comply with the operational and administrative requirements of participation in the study (based on the judgment of the investigators).
- Terminal illness associated with expected survival of <12 months.
Trial locations and contacts
1 site in 1 country.
United States1 site
UT Center of Excellence on Mood Disorders
Houston, Texas, 77054
About this study
Official title: Deep Brain Stimulation (DBS) Therapy for Treatment Resistant
We propose a clinical study of medial forebrain bundle DBS as a treatment in 20 patients with treatment refractory depression (TRD). Data from the University of Bonn indicates that surgical lesions of the medical forebrain bundle can produce therapeutic benefits in patients with depressive disorders, and suggest that DBS at the same site may also reduce symptomatology in these TRD patients (Schaepfer, 2013). Depression affects up to 10% of the US population and of those at least 10-15% do not benefit from therapies hence why we must explore new treatments. The Percept™ PC system manufactured by Medtronic Neurological will be used in this study. Study subjects will be between the ages of 22 and 70 years of age and suffer from TRD, have failed multiple treatment regimens, including ECT, and remain symptomatic. Those identified as TRD patients will then be enrolled in a clinical pilot study investigating DBS, targeting the MFB.
Read the detailed description
Study Design: Subjects will be ten patients with MDD identified via the Structured Clinical Interview for DSM-IV, manifesting a current major depressive episode of disabling severity, refractory to prolonged treatment trials with conventional medication, electro-convulsive therapy (ECT) and psychotherapy. A marked impact of depression on their health and functional status will be evidenced by major impairment in functioning or potentially severe medical outcomes (repeated hospitalizations, serious suicidal or other self-injurious behavior). They will be recruited from individuals currently seen at our facility or referred by psychiatrists in the community. Patients will be initially screened by a comprehensive review of their psychiatric history, obtained by interview of the patient, family and treating psychiatrist and/or psychologist, as well as by obtaining and reviewing all available records of previous psychiatric treatment. The available generally-accepted alternative treatments for depression are pharmacologic therapy, psychotherapy, and ECT. Failed trials of multiple proven pharmacologic treatments, an adequate course of psychotherapy, and an adequate course of bilateral ECT (or inability to tolerate an adequate ECT trial) are inclusion criteria for all candidates who are considered for this study. However, as alternatives to participation in this study, candidates may undertake additional trials of potentially beneficial novel combinations of medication and psychotherapy, or they may undertake trials of novel interventions lacking definitive evidence of efficacy in severe depression (e.g., light therapy, herbal therapy, transcranial magnetic stimulation, vagal nerve stimulation). The protocol was designed to include four phases. All patients will enter these phases in the same sequence. The experimental design is illustrated in the timeline in Figure 1. Surgical implantation will be followed by: 1) Baseline Phase (a 1 month period with no stimulation); 2) Variable Staggered Phase (blinded stimulation onset starting from 1 month to 3 months post implant, with optimal parameter determination during this time ; 3) Initial Chronic Phase (blinded bilateral stimulation, lasting at least three months) (see below); 4) Continuation Phase (unblinded active bilateral or unilateral stimulation to maximize clinical response) Protocol overview and design: We propose a clinical study of medial forebrain bundle DBS as a treatment in 10 patients with treatment refractory depression (TRD). Data from the University of Bonn indicates that surgical lesions of the medical forebrain bundle can produce therapeutic benefits in patients with depressive disorders, and suggest that DBS at the same site may also reduce symptomatology in these TRD patients (Schaepfer, 2013). Depression affects up to 10% of the US population and of those at least 10-15% do not benefit from therapies hence why we must explore new treatments. The Percept™ PC system manufactured by Medtronic Neurological will be used in this study. Those identified as TRD patients will then be enrolled in a clinical pilot study investigating DBS, targeting the MFB.
- Being tested
- Deep Brain Stimulation Model 3387 Model 3389
- Keywords
- Deep Brain Stimulation, Treatment Resistant Depression, Major Depressive Disorder, Depression, ECT, TNS
- Medical subject headings
- Depressive Disorder, Major, Depressive Disorder, Treatment-Resistant, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Deep Brain Stimulation Model 3387 Model 3389Device
Also called Medtronic Neuromodulation
Implantation of all devices will be performed at a single session. Lead implantation will take place under local anesthesia, with implanted pulse generator (IPG) implantation under general anesthesia. The stereotaxic frame will be fitted on the day of surgery, following standard stereotactic surgical procedure. The leads will be inserted so that the stimulation sites span superolateral median forebrain bundle.
| Study group | Role | What they receive |
|---|---|---|
| Deep Brain Stimulation | Experimental | Device implantation (Deep Brain Stimulation Model 3387 Model 3389) Receives: Device: Deep Brain Stimulation Model 3387 Model 3389 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in patients MADRS scores
We will assess individual patient response, measured by standardized patient and clinician ratings of depression severity, under blinded conditions. Prospective ratings using validated and reliable measures of symptoms, quality of life and safety will be employed. We will assess safety for all subjects by monitoring any adverse events.
Measured: weekly (24 Months)
Secondary outcomes (6)
Accuracy of Electrode placement
We will implant the Model 3387/Model 3389 lead at this target location, with the exact choice of lead to be determined during surgery.
Measured: Post-operation (weekly for 24 months)
Frequency and Charge of Stimulation
The optimal stimulation parameters for reducing depressive symptoms acutely and chronically are unknown. Preliminary data suggest that psychiatric patients who have responded to DBS have responded at high frequencies and amplitudes that presumably induce a depolarization block or "neuronal jamming," and thus mimic a lesion. We intend to explore the effects of a wide range of frequencies and amplitudes during the acute testing phase and to utilize high frequency continuous stimulation at the lowest amplitude that results in a definitive effect in the chronic phase of the study.
Measured: Weekly (24 months total)
Determine Feasibility of a Double Blind Study
We hypothesize that it will be possible to develop a suitable double-blind procedure by which neither patients nor physicians will know whether DBS is on or off at any given moment.
Measured: 24 months
Decrease in Neurocognitive scores on CSTC
In this study, neuropsychological tests believed sensitive to changes in Concept Shifting Test-Combined (CSTC) function, and particularly orbitofrontal function, will be obtained with the stimulator on and off, if possible, under blinded conditions. In a separate study, positron emission tomography (PET) perfusion imaging and neuropsychological tests will be obtained to determine how corticobasal brain function changes after acute and chronic DBS.
Measured: pre-operative, 12 month and 24 months post-operation
Assess maintenance of treatment response (or remission) associated with chronic DBS:
Maintaining Treatment Response
Measured: 6, 12, and 24 months
Number of Adverse Events
Measured: 24 months (reported weekly)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2014 (estimated)
- Study start16 Dec 2013
- Primary completion1 Apr 2027 (estimated)
- Study completion1 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The University of Texas Health Science Center, Houston
- Sponsor type
- University, hospital or other
- Collaborators
- Medtronic
- Responsible party
- Principal investigator, Jair Soares, The University of Texas Health Science Center, Houston
- Investigators
- Jair C Soares, MD, PhD, Principal investigator, The University of Texas Health Science Center, HoustonJoao Quevedo, MD, PhD, Study director, The University of Texas Health Science Center, HoustonGiovana Zunta Soares, MD, Study director, The University of Texas Health Science Center, Houston
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02046330
- Sponsor's protocol ID
- HSC-MS-13-0004
- Status last verified
- Feb 2026
- First submitted
- 17 Dec 2013
- Last updated
- 23 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Fenoy AJ, Schulz P, Selvaraj S, Burrows C, Spiker D, Cao B, Zunta-Soares G, Gajwani P, Quevedo J, Soares J. Deep brain stimulation of the medial forebrain bundle: Distinctive responses in resistant depression. J Affect Disord. 2016 Oct;203:143-151. doi: 10.1016/j.jad.2016.05.064. Epub 2016 Jun 3.
PubMed 27288959
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Deep Brain Stimulation (DBS) Therapy for Treatment Resistant
- ClinicalTrials.gov ID
- NCT02046330
- Acronym / sponsor ID
- HSC-MS-13-0004
- Keywords
- Deep Brain Stimulation, Treatment Resistant Depression, Major Depressive Disorder, Depression, ECT, TNS
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 16 participants (estimated)
- Lead sponsor
- The University of Texas Health Science Center, HoustonUniversity, hospital or other
- Collaborators
- Medtronic
- Study start
- 16 Dec 2013 (actual)
- Primary completion
- 1 Apr 2027 (estimated)
- Study completion
- 1 Apr 2027 (estimated)
- First posted
- 27 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
We propose a clinical study of medial forebrain bundle DBS as a treatment in 20 patients with treatment refractory depression (TRD). Data from the University of Bonn indicates that surgical lesions of the medical forebrain bundle can produce therapeutic benefits in patients with depressive disorders, and suggest that DBS at the same site may also reduce symptomatology in these TRD patients (Schaepfer, 2013). Depression affects up to 10% of the US population and of those at least 10-15% do not benefit from therapies hence why we must explore new treatments. The Percept™ PC system manufactured by Medtronic Neurological will be used in this study. Study subjects will be between the ages of 22 and 70 years of age and suffer from TRD, have failed multiple treatment regimens, including ECT, and remain symptomatic. Those identified as TRD patients will then be enrolled in a clinical pilot study investigating DBS, targeting the MFB.
Detailed description
Study Design: Subjects will be ten patients with MDD identified via the Structured Clinical Interview for DSM-IV, manifesting a current major depressive episode of disabling severity, refractory to prolonged treatment trials with conventional medication, electro-convulsive therapy (ECT) and psychotherapy. A marked impact of depression on their health and functional status will be evidenced by major impairment in functioning or potentially severe medical outcomes (repeated hospitalizations, serious suicidal or other self-injurious behavior). They will be recruited from individuals currently seen at our facility or referred by psychiatrists in the community. Patients will be initially screened by a comprehensive review of their psychiatric history, obtained by interview of the patient, family and treating psychiatrist and/or psychologist, as well as by obtaining and reviewing all available records of previous psychiatric treatment. The available generally-accepted alternative treatments for depression are pharmacologic therapy, psychotherapy, and ECT. Failed trials of multiple proven pharmacologic treatments, an adequate course of psychotherapy, and an adequate course of bilateral ECT (or inability to tolerate an adequate ECT trial) are inclusion criteria for all candidates who are considered for this study. However, as alternatives to participation in this study, candidates may undertake additional trials of potentially beneficial novel combinations of medication and psychotherapy, or they may undertake trials of novel interventions lacking definitive evidence of efficacy in severe depression (e.g., light therapy, herbal therapy, transcranial magnetic stimulation, vagal nerve stimulation). The protocol was designed to include four phases. All patients will enter these phases in the same sequence. The experimental design is illustrated in the timeline in Figure 1. Surgical implantation will be followed by: 1) Baseline Phase (a 1 month period with no stimulation); 2) Variable Staggered Phase (blinded stimulation onset starting from 1 month to 3 months post implant, with optimal parameter determination during this time ; 3) Initial Chronic Phase (blinded bilateral stimulation, lasting at least three months) (see below); 4) Continuation Phase (unblinded active bilateral or unilateral stimulation to maximize clinical response) Protocol overview and design: We propose a clinical study of medial forebrain bundle DBS as a treatment in 10 patients with treatment refractory depression (TRD). Data from the University of Bonn indicates that surgical lesions of the medical forebrain bundle can produce therapeutic benefits in patients with depressive disorders, and suggest that DBS at the same site may also reduce symptomatology in these TRD patients (Schaepfer, 2013). Depression affects up to 10% of the US population and of those at least 10-15% do not benefit from therapies hence why we must explore new treatments. The Percept™ PC system manufactured by Medtronic Neurological will be used in this study. Those identified as TRD patients will then be enrolled in a clinical pilot study investigating DBS, targeting the MFB.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Deep Brain Stimulation | Experimental | Device: Deep Brain Stimulation Model 3387 Model 3389Device implantation (Deep Brain Stimulation Model 3387 Model 3389) |
Who may qualify
- Ages
- 22 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Major Depression Disorder (MDD) diagnosed by Structured Clinical Interview for DSM-IV (SCID I/DSM-IV), judged to be of disabling severity.
- Age 22 - 70 years.
- 24-item Hamilton Depression Rating Scale (HDRS) score of at least 21 on the first 17 items
- Global Assessment of Function (GAF) score of 45 or less.
- A recurrent (equal or >4 episodes) or chronic (episode duration equal or higher >2 years) course AND a minimum of 5 years since the onset of the first depressive episode. Major impairment in functioning or potentially severe medical outcomes (repeated hospitalizations, serious suicidal or other self-injurious behavior).
Key exclusion criteria (17 listed)
- Current or past non-affective psychotic disorder, Bipolar Disorder, Schizophrenia, or Schizoaffective disorder. Patients who suffer from generalized anxiety disorder will be permitted to participate as long as MDD is the primary clinical diagnosis.
- Any current clinically significant neurological disorder, including dementia or medical illness affecting brain function.
- Any clinically significant abnormality on preoperative magnetic resonance imaging (MRI).
- Any previous surgery to destroy the region of the brain that will be the target of treatment.
- Any surgical contraindications to undergoing DBS, including labeled contraindications for DBS and/or inability to undergo presurgical MRI (cardiac pacemaker, implantable defibrillator or other implantable stimulator, pregnancy, metal in body, severe claustrophobia), infection, coagulopathy, inability to undergo an awake operation, significant cardiac or other medical risk factors for surgery.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Deep Brain Stimulation Model 3387 Model 3389Also: Medtronic NeuromodulationImplantation of all devices will be performed at a single session. Lead implantation will take place under local anesthesia, with implanted pulse generator (IPG) implantation under general anesthesia. The stereotaxic frame will be fitted on the day of surgery, following standard stereotactic surgical procedure. The leads will be inserted so that the stimulation sites span superolateral median forebrain bundle. | Device | Deep Brain Stimulation |
Primary outcome
Changes in patients MADRS scores
Time frame: weekly (24 Months)
We will assess individual patient response, measured by standardized patient and clinician ratings of depression severity, under blinded conditions. Prospective ratings using validated and reliable measures of symptoms, quality of life and safety will be employed. We will assess safety for all subjects by monitoring any adverse events.
6 secondary outcomes
Accuracy of Electrode placement
Time frame: Post-operation (weekly for 24 months)
Frequency and Charge of Stimulation
Time frame: Weekly (24 months total)
Determine Feasibility of a Double Blind Study
Time frame: 24 months
Decrease in Neurocognitive scores on CSTC
Time frame: pre-operative, 12 month and 24 months post-operation
Assess maintenance of treatment response (or remission) associated with chronic DBS:
Time frame: 6, 12, and 24 months
Number of Adverse Events
Time frame: 24 months (reported weekly)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2026.
- Derived from this study: PubMed 27288959Fenoy AJ, Schulz P, Selvaraj S, Burrows C, Spiker D, Cao B, Zunta-Soares G, Gajwani P, Quevedo J, Soares J. Deep brain stimulation of the medial forebrain bundle: Distinctive responses in resistant depression. J Affect Disord. 2016 Oct;203:143-151. doi: 10.1016/j.jad.2016.05.064. Epub 2016 Jun 3.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jair C Soares, MD, PhD principal investigator
The University of Texas Health Science Center, Houston
Joao Quevedo, MD, PhD study director
The University of Texas Health Science Center, Houston
Giovana Zunta Soares, MD study director
The University of Texas Health Science Center, Houston
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Deep Brain Stimulation Model 3387 Model 3389 in people with Major Depressive Disorder and Treatment Resistant Depression, run by The University of Texas Health Science Center, Houston at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 23 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in patients MADRS scores (time frame: weekly (24 Months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02046330, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2026.