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Treatment Resistant DepressionPhase 3DRIVERNCT02889250

Deep Brain Stimulation to Relieve Depression

A Phase 3 study testing Medtronic Activa SC DBS, Lead Model 3387 in people with Treatment Resistant Depression, run by Jordan F. Karp.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This is an open label study with a sample size of 6 to develop deep brain stimulation of the subcallosal cingulate white matter(SCCWM) for late life depression using an experimental medicine approach in which the investigators will program the device based both on 1) a neurophysiologic measure of target engagement and… Read more about this study

Who is it for?
Ages 60 years and older
Conditions the study is for
Treatment Resistant Depression
What is being tested?
Medtronic Activa SC DBS, Lead Model 3387
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Jun 2018to Mar 2020
Phase
Phase 3
Are there results?
None posted in the registry

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 60 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subject has signed and dated the Screening Consent Form prior to conducting any study-related screening testing
  • Following successful completion of the screening phase, subject has signed and dated the Study Informed Consent Form prior to the initiation of any study-related procedures (other than screening testing).
  • Subject has been medically cleared for DBS neurosurgical procedure by their primary care doctor and study neurosurgeon.
  • Age >/= 60 years old.
  • Subject is fluent in English (written and verbal).
  • Subject meets Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) diagnostic criteria for major depressive disorder (MDD) based on Structured Clinical Interview for DSM-5 Axis I Disorders (SCID-I) conducted during the screening testing for the project.
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  • Subject has medical record documentation that the current major depressive episode (MDE) has persisted for > 2 years with the exception of brief responses (e.g., < 8 weeks) to treatments.
  • Subject's depression is treatment resistant; the subject has not clinical responded to 4 or more adequate drug trials of therapy for depression as scored by the antidepressant treatment history form.
  • Three of the 4 trials need to have occurred in the current depressive episode.
  • One of the 4 trials must have included a combination of 2 or more antidepressant medications from 2 different antidepressant classes.
  • One of the 4 trials must have included 1 of the following: augmentation agents: lithium, triiodothyronine, buspirone, bupropion, or atypical antipsychotic.
  • Subject must have tried a course of ECT.
  • Subject's antidepressant medication regimen has been held stable for > 30 days prior to the study screening MADRS.
  • Subject's screening MADRS score > 25.
  • Average pre-operative MADRS score of 25 or greater (averaged over at least four weekly pre-surgical evaluations during the weeks prior to surgery) .
  • Aggregate score of > 8 on the social life and family life/home responsibilities subscales of the Sheehan Disability Scale.
  • Subject has received > 6 weeks of psychotherapy treatment, for the current or a previous depressive episode, without significant improvement.
  • Female subjects must not be pregnant, and if still of child bearing potential, must agree to a form of medically acceptable contraception.
  • If subject has a vagus nerve stimulator (VNS) implanted, they must agree to have the VNS system removed.
  • Subject agrees to not change psychotropic medication, psychotherapy, and outpatient psychiatric care program regimen throughout the screening phase and for the first six months after implantation of the DBS device.
  • Subject agrees to have the DRIVER investigators be the sole prescriber of psychotropic medications during the course of the study.
  • Evidence of connectivity (tractography identified streamlines) that is not disrupted by a significant burden of white matter hyperintensities between the SCC and nodes that may mediate response to DBS including MFC, dorsal and rostral cingulate, and subcortical nuclei.
  • Availability of an informant is required for study participation

Who cannot join

  • Inability to provide informed consent.
  • Inability to tolerate general anesthesia.
  • Subject has been hospitalized for treatment of depression < 30 days prior to the screening testing.
  • Active suicidal ideation with intent, suicide attempt within the last six months, or more than three suicide attempts within the last two years. Urgent psychiatric referral will be made in these cases.
  • Subject made a suicide attempt requiring medical treatment < 3 months prior to the screening testing.
  • Subject has a history of 2 or more suicide attempts < 12 months prior to the screening testing.
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  • Subject poses an imminent suicide risk in the opinion of the investigator.
  • Subject is currently enrolled in or plans to enroll in any concurrent drug and/or device study that may confound the results of this study.
  • Subject has a history of a seizure disorder.
  • Subject will be exposed to diathermy.
  • Subject has a history of a neurosurgical ablation procedure.
  • Subject has a life expectancy of < 3 years.
  • Significant cerebrovascular risk factors or history of stroke, major head trauma, neurodegenerative disorder, or other general contraindications for DBS surgery (cardiac pacemaker/defibrillator or other Ferromagnetic implanted devices).
  • Contraindication to MRI.
  • Dementia, as defined by Modified Mini Mental State Examination (3MS) < 84 and clinical evidence of dementia. Patients screened out due to possible dementia will be referred to the local Memory Clinic or Alzheimer's Disease Research Center for evaluation to clarify the presence or absence of dementia.
  • Lifetime diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms, obsessive compulsive disorder, panic disorder or post-traumatic stress disorder, or generalized anxiety disorder not secondary to the depression, as diagnosed by the SCID. A recommendation for psychiatric referral will be made in these cases.
  • Substance misuse (except for nicotine or caffeine) not in full sustained remission for at least one year as determined by SCID, and confirmed by study physician interview.
  • Anticoagulant pharmacotherapy.
  • Subjects that are determined during the screening phases to have severe personality disorders may be excluded.
  • Final patient selection will be made by consensus of the multidisciplinary study team. No exclusion criteria are based on race, ethnicity, or gender.

About this study

This is an open label study with a sample size of 6 to develop deep brain stimulation of the subcallosal cingulate white matter(SCCWM) for late life depression using an experimental medicine approach in which the investigators will program the device based both on 1) a neurophysiologic measure of target engagement and 2) safety (defined as lack of neuropsychiatric worsening and stable neurocognition).

Read the detailed description

Late-life treatment resistant depression (LL-TRD) is a public health and clinical dilemma.

Older patients with TRD are: 1) at greater risk for morbidity from medications and ECT, and 2) more likely to require maintenance ECT (which carries risks of cognitive impairment and repeated exposure to general anesthesia), compared to younger depressed patients. There is great need to develop targeted and safe treatments for those with LLTRD.

Deep brain stimulation (DBS) is a neurosurgical intervention with potential to become a treatment option for appropriately selected patients with LL-TRD. To date, the subcallosal cingulate white matter (SCCWM) is the DBS target with the most clinical, safety, and neurophysiologic data supporting therapeutic efficacy. The SCC is considered a "governor" for a network implicated in the processing of negative emotions and symptoms of depression. Furthermore, structural and functional impairments of the SCC and connected network structures are associated with LLD, supporting its potential as a target for DBS in older adults.

The overarching aim for this project is to develop DBS of the SCCWM for LL-TRD using an experimental medicine approach in which the investigators will program the device based both on 1) a neurophysiologic measure of target engagement and 2) safety (defined as lack of neuropsychiatric worsening and stable neurocognition). The proposed biomarker of target engagement is theta cordance (TC), a composite of absolute and relative theta power that is strongly correlated with regional neural metabolism. The hypothesis is that TC will increase during DBS is based on the observation of increased frontal TC during DBS in combination with PET data, which showed increased metabolism in frontal cortical structures in responders to DBS.

The investigators will use magnetoencephalography to measure TC during DBS and then will adjust stimulation settings to optimize target engagement over the course of the study, in response to observed increases in TC. Adding to the novelty of the project is use of personalized tractography to guide precise electrode placement in the area of the SCCWM which contain white matter tracts to mood-relevant frontal and subcortical nuclei.

During the two years of this open-label project the investigators will implant 6 patients. For each subject, over the course of 6 months, the investigators will ascertain the dose range effect of escalating DBS stimulation parameters on both TC and measures of safety.

Being tested
Medtronic Activa SC DBS, Lead Model 3387
Keywords
geriatric, depression, deep brain stimulation, subcallosal cingulate
Medical subject headings
Depressive Disorder, Treatment-Resistant, Depression

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Medtronic Activa SC DBS, Lead Model 3387Device

    Deep Brain Stimulation

Study groups in NCT02889250
Study groupRoleWhat they receive
Open Label DBSExperimental6 months of DBS
Receives: Device: Medtronic Activa SC DBS, Lead Model 3387

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Theta cordance, measured by magnetoencephalography.

    Theta cordance combines complementary information from absolute (the amount of power in the theta oscillatory band and relative power (the percentage of power contained in the theta band relative to the total spectrum) of EEG spectra.

    Measured: 6 months

  2. Symptoms of Depression

    A measure of safety is that the stimulation does not worsen depression. Significant worsening of depressive symptoms is defined as >/= 30% worsening of symptoms, as measured with the Montgomery Asberg Depression Rating Scale (MADRS) for four consecutive weeks, compared to the average score of the 4 weeks pre-stimulation.

    Measured: 6 months

  3. Suicidality

    A measure of safety is that the stimulation does not worsen or cause suicidal ideation or behavior. The Columbia Suicide Severity Rating Scale will assess suicidality. Clinically significant suicidality is defined as greater than 3 on suicidal ideation subscale of the Columbia Suicide Severity Scale AND worsening of the score compared to baseline, OR any suicidal behavior noted on the suicidal behavior subscale.

    Measured: 6 months

  4. Neurocognitive status

    A measure of safety is that the stimulation does not worsen neurocognition. The investigators will use a comprehensive validated battery of neuropsychiatric tests to monitor change in memory, executive functioning, psychomotor speed, verbal ability and global cognitive functioning. Clinically significant worsening is defined as deterioration of > 1 SD in at least two cognitive domains after six months of stimulation, compared to pre-surgical testing.

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Sep 2016 (estimated)
  2. Study startJun 2018 (estimated)
  3. Primary completionDec 2019 (estimated)
  4. Study completionMar 2020 (estimated)

Why it stopped: did not receive funding

Resources

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 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02889250
Sponsor's protocol ID
PRO16050040
Acronym
DRIVER
Status last verified
Aug 2018
First submitted
13 Aug 2016
Last updated
6 Aug 2018
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
Yes
Individual data sharing
Yes: The investigators will not share individual participant data. The investigators have a data sharing policy consistent with requirements of NIH.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Medtronic Activa SC DBS, Lead Model 3387 in people with Treatment Resistant Depression, run by Jordan F. Karp.

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 23 inclusion and 20 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: withdrawn, as of the sponsor's last update on 6 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.

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.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

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?

Theta cordance, measured by magnetoencephalography. (time frame: 6 months). The study lists 4 primary outcomes in all. 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 NCT02889250.

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 6 Aug 2018.

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